Glucose Regulation Pathway | Genes, Symptoms, and Follow-Up

GCKR2 SNPs - 6 claimsShow SNPs

rs12603263 claims - 12 study rows

biomarker tendency - TT

GCKR biomarker tendency

Strong

rs1260326 TT is associated with increased GCKR biomarker tendency.

GCKR rs1260326 T-containing genotypes are scored as a stronger GCKR-linked biomarker tendency, mainly higher triglycerides with lower fasting glucose in population studies.

Likely effectHigher biomarker tendency

Signal sizeSmall signal

Evidence supportStrong support

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data identify rs1260326 at GCKR, the glucokinase regulator gene. The commonly reported genotype letters for this coding variant are CC, CT, and TT.PMC2570409biomarker association - loose proxyOrho-Melander et al. reported that rs1260326, also described as Pro446Leu, was the strongest GCKR-region association signal and linked the T allele to higher triglycerides and lower fasting glucose across multiple cohorts.PMC2918876biomarker association - close proxyPollin et al. studied a high-fat challenge and reported that the rs1260326 T allele was associated with higher fasting triglycerides and a stronger postprandial triglyceride response. This supports allele-dose scoring for a triglyceride-related biomarker tendency.PMC3720952biomarker association - close proxyThe HALCyon Programme confirmed associations between rs1260326 and triglycerides and glucose in middle-aged to older adults, while also noting environmental modification. This supports a biomarker-tendency interpretation rather than a fixed health outcome.

biomarker tendency - CT

GCKR biomarker tendency

Strong

rs1260326 CT is associated with increased GCKR biomarker tendency.

GCKR rs1260326 T-containing genotypes are scored as a stronger GCKR-linked biomarker tendency, mainly higher triglycerides with lower fasting glucose in population studies.

Likely effectHigher biomarker tendency

Signal sizeSmall signal

Evidence supportStrong support

Report useIncluded in pathway scoring

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data identify rs1260326 at GCKR, the glucokinase regulator gene. The commonly reported genotype letters for this coding variant are CC, CT, and TT.PMC2570409biomarker association - loose proxyOrho-Melander et al. reported that rs1260326, also described as Pro446Leu, was the strongest GCKR-region association signal and linked the T allele to higher triglycerides and lower fasting glucose across multiple cohorts.PMC2918876biomarker association - close proxyPollin et al. studied a high-fat challenge and reported that the rs1260326 T allele was associated with higher fasting triglycerides and a stronger postprandial triglyceride response. This supports allele-dose scoring for a triglyceride-related biomarker tendency.PMC3720952biomarker association - close proxyThe HALCyon Programme confirmed associations between rs1260326 and triglycerides and glucose in middle-aged to older adults, while also noting environmental modification. This supports a biomarker-tendency interpretation rather than a fixed health outcome.

biomarker tendency - CC

GCKR biomarker tendency

Not used for pathway scoring

rs1260326 CC has no scored directional claim for GCKR biomarker tendency.

GCKR rs1260326 T-containing genotypes are scored as a stronger GCKR-linked biomarker tendency, mainly higher triglycerides with lower fasting glucose in population studies.

Likely effectNo clear biomarker tendency

Signal sizeMinimal signal

Evidence supportVery limited support

Report useEvidence only, not scored

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data identify rs1260326 at GCKR, the glucokinase regulator gene. The commonly reported genotype letters for this coding variant are CC, CT, and TT.PMC2570409biomarker association - loose proxyOrho-Melander et al. reported that rs1260326, also described as Pro446Leu, was the strongest GCKR-region association signal and linked the T allele to higher triglycerides and lower fasting glucose across multiple cohorts.PMC2918876biomarker association - close proxyPollin et al. studied a high-fat challenge and reported that the rs1260326 T allele was associated with higher fasting triglycerides and a stronger postprandial triglyceride response. This supports allele-dose scoring for a triglyceride-related biomarker tendency.PMC3720952biomarker association - close proxyThe HALCyon Programme confirmed associations between rs1260326 and triglycerides and glucose in middle-aged to older adults, while also noting environmental modification. This supports a biomarker-tendency interpretation rather than a fixed health outcome.

rs7800943 claims - 12 study rows

biomarker tendency - TT

GCKR biomarker tendency

Strong

rs780094 TT is associated with increased GCKR biomarker tendency.

GCKR rs780094 T-containing genotypes are scored as a stronger GCKR-linked biomarker tendency, mainly higher triglycerides with lower fasting glucose in population studies.

Likely effectHigher biomarker tendency

Signal sizeSmall signal

Evidence supportStrong support

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data identify rs780094 at GCKR, the glucokinase regulator gene. The commonly reported genotype letters for end-user literature are CC, CT, and TT.PMC2570409biomarker association - close proxyOrho-Melander et al. reported that rs780094 in the GCKR region was associated with opposite effects on fasting triglycerides and glucose, with the T allele linked to higher triglycerides and lower fasting glucose.PMC2908550biomarker association - loose proxyThe ARIC Study replicated rs780094 T-allele associations with lower fasting glucose, insulin, insulin resistance, and prevalent diabetes, while also reporting higher triglycerides and C-reactive protein in white participants.PMC3720952biomarker association - loose proxyThe HALCyon Programme reviewed rs780094 as one of the GCKR variants tied to metabolic traits and confirmed the closely related functional GCKR signal for triglyceride and glucose measures. This supports conservative biomarker-tendency scoring.

biomarker tendency - CT

GCKR biomarker tendency

Moderate

rs780094 CT is associated with increased GCKR biomarker tendency.

GCKR rs780094 T-containing genotypes are scored as a stronger GCKR-linked biomarker tendency, mainly higher triglycerides with lower fasting glucose in population studies.

Likely effectHigher biomarker tendency

Signal sizeSmall signal

Evidence supportStrong support

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data identify rs780094 at GCKR, the glucokinase regulator gene. The commonly reported genotype letters for end-user literature are CC, CT, and TT.PMC2570409biomarker association - close proxyOrho-Melander et al. reported that rs780094 in the GCKR region was associated with opposite effects on fasting triglycerides and glucose, with the T allele linked to higher triglycerides and lower fasting glucose.PMC2908550biomarker association - loose proxyThe ARIC Study replicated rs780094 T-allele associations with lower fasting glucose, insulin, insulin resistance, and prevalent diabetes, while also reporting higher triglycerides and C-reactive protein in white participants.PMC3720952biomarker association - loose proxyThe HALCyon Programme reviewed rs780094 as one of the GCKR variants tied to metabolic traits and confirmed the closely related functional GCKR signal for triglyceride and glucose measures. This supports conservative biomarker-tendency scoring.

biomarker tendency - CC

GCKR biomarker tendency

Not used for pathway scoring

rs780094 CC has no scored directional claim for GCKR biomarker tendency.

GCKR rs780094 T-containing genotypes are scored as a stronger GCKR-linked biomarker tendency, mainly higher triglycerides with lower fasting glucose in population studies.

Likely effectNo clear biomarker tendency

Signal sizeMinimal signal

Evidence supportVery limited support

Report useEvidence only, not scored

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data identify rs780094 at GCKR, the glucokinase regulator gene. The commonly reported genotype letters for end-user literature are CC, CT, and TT.PMC2570409biomarker association - close proxyOrho-Melander et al. reported that rs780094 in the GCKR region was associated with opposite effects on fasting triglycerides and glucose, with the T allele linked to higher triglycerides and lower fasting glucose.PMC2908550biomarker association - loose proxyThe ARIC Study replicated rs780094 T-allele associations with lower fasting glucose, insulin, insulin resistance, and prevalent diabetes, while also reporting higher triglycerides and C-reactive protein in white participants.PMC3720952biomarker association - loose proxyThe HALCyon Programme reviewed rs780094 as one of the GCKR variants tied to metabolic traits and confirmed the closely related functional GCKR signal for triglyceride and glucose measures. This supports conservative biomarker-tendency scoring.

MTNR1B2 SNPs - 6 claimsShow SNPs

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rs108309633 claims - 9 study rows

biomarker tendency - GG

MTNR1B biomarker tendency

Strong

rs10830963 GG is associated with increased MTNR1B biomarker tendency.

MTNR1B rs10830963 is scored as a glycemic-response biomarker tendency for G-containing genotypes, stronger for GG than CG.

Likely effectHigher biomarker tendency

Signal sizeSmall signal

Evidence supportStrong support

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data place rs10830963 in MTNR1B and annotate common C and G alleles, with intronic transcript annotations. This supports using CC, CG, and GG genotype letters for this simplified record.PubMed 19324940biomarker association - close proxyA study of 19,605 Europeans reported that the rs10830963 G allele was associated with higher fasting plasma glucose, impaired fasting glycemia, type 2 diabetes association, and lower glucose-stimulated insulin release. This supports a G-allele-dose biomarker-tendency score.PubMed 19060908gwas - loose proxyA Nature Genetics study reported that the MTNR1B risk genotype was associated with impaired early insulin response and increased MTNR1B expression in human islets. This supports a glucose-regulation biomarker tendency rather than a standalone diagnosis.

biomarker tendency - CG

MTNR1B biomarker tendency

Moderate

rs10830963 CG is associated with increased MTNR1B biomarker tendency.

MTNR1B rs10830963 is scored as a glycemic-response biomarker tendency for G-containing genotypes, stronger for GG than CG.

Likely effectHigher biomarker tendency

Signal sizeSmall signal

Evidence supportStrong support

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data place rs10830963 in MTNR1B and annotate common C and G alleles, with intronic transcript annotations. This supports using CC, CG, and GG genotype letters for this simplified record.PubMed 19324940biomarker association - close proxyA study of 19,605 Europeans reported that the rs10830963 G allele was associated with higher fasting plasma glucose, impaired fasting glycemia, type 2 diabetes association, and lower glucose-stimulated insulin release. This supports a G-allele-dose biomarker-tendency score.PubMed 19060908gwas - loose proxyA Nature Genetics study reported that the MTNR1B risk genotype was associated with impaired early insulin response and increased MTNR1B expression in human islets. This supports a glucose-regulation biomarker tendency rather than a standalone diagnosis.

biomarker tendency - CC

MTNR1B biomarker tendency

Not used for pathway scoring

rs10830963 CC has no scored directional claim for MTNR1B biomarker tendency.

MTNR1B rs10830963 is scored as a glycemic-response biomarker tendency for G-containing genotypes, stronger for GG than CG.

Likely effectNo clear biomarker tendency

Signal sizeMinimal signal

Evidence supportVery limited support

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data place rs10830963 in MTNR1B and annotate common C and G alleles, with intronic transcript annotations. This supports using CC, CG, and GG genotype letters for this simplified record.PubMed 19324940biomarker association - close proxyA study of 19,605 Europeans reported that the rs10830963 G allele was associated with higher fasting plasma glucose, impaired fasting glycemia, type 2 diabetes association, and lower glucose-stimulated insulin release. This supports a G-allele-dose biomarker-tendency score.PubMed 19060908gwas - loose proxyA Nature Genetics study reported that the MTNR1B risk genotype was associated with impaired early insulin response and increased MTNR1B expression in human islets. This supports a glucose-regulation biomarker tendency rather than a standalone diagnosis.

rs13871533 claims - 9 study rows

biomarker tendency - TT

MTNR1B biomarker tendency

Moderate

rs1387153 TT is associated with increased MTNR1B biomarker tendency.

MTNR1B-nearby rs1387153 is scored as a modest fasting-glucose biomarker tendency for T-containing genotypes, stronger for TT than CT.

Likely effectHigher biomarker tendency

Signal sizeSmall signal

Evidence supportModerate support

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data annotate rs1387153 as a common C/T variant on chromosome 11 near the MTNR1B locus. This supports using CC, CT, and TT genotype letters for this simplified record.PubMed 19060909biomarker association - close proxyA Nature Genetics study identified rs1387153 near MTNR1B as a fasting plasma glucose signal and reported that the T allele was associated with higher fasting glucose and type 2 diabetes association estimates. This supports a T-allele-dose biomarker-tendency score.PubMed 19060907biomarker association - close proxyA companion MTNR1B fasting-glucose study reported strong association at the MTNR1B locus and highlighted rs10830963 as the strongest signal, while noting rs1387153 among exchanged MTNR1B signals. This supports treating rs1387153 as a nearby biomarker signal with modest certainty.

biomarker tendency - CT

MTNR1B biomarker tendency

Moderate

rs1387153 CT is associated with increased MTNR1B biomarker tendency.

MTNR1B-nearby rs1387153 is scored as a modest fasting-glucose biomarker tendency for T-containing genotypes, stronger for TT than CT.

Likely effectHigher biomarker tendency

Signal sizeSmall signal

Evidence supportModerate support

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data annotate rs1387153 as a common C/T variant on chromosome 11 near the MTNR1B locus. This supports using CC, CT, and TT genotype letters for this simplified record.PubMed 19060909biomarker association - close proxyA Nature Genetics study identified rs1387153 near MTNR1B as a fasting plasma glucose signal and reported that the T allele was associated with higher fasting glucose and type 2 diabetes association estimates. This supports a T-allele-dose biomarker-tendency score.PubMed 19060907biomarker association - close proxyA companion MTNR1B fasting-glucose study reported strong association at the MTNR1B locus and highlighted rs10830963 as the strongest signal, while noting rs1387153 among exchanged MTNR1B signals. This supports treating rs1387153 as a nearby biomarker signal with modest certainty.

biomarker tendency - CC

MTNR1B biomarker tendency

Not used for pathway scoring

rs1387153 CC has no scored directional claim for MTNR1B biomarker tendency.

MTNR1B-nearby rs1387153 is scored as a modest fasting-glucose biomarker tendency for T-containing genotypes, stronger for TT than CT.

Likely effectNo clear biomarker tendency

Signal sizeMinimal signal

Evidence supportVery limited support

Report useEvidence only, not scored

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data annotate rs1387153 as a common C/T variant on chromosome 11 near the MTNR1B locus. This supports using CC, CT, and TT genotype letters for this simplified record.PubMed 19060909biomarker association - close proxyA Nature Genetics study identified rs1387153 near MTNR1B as a fasting plasma glucose signal and reported that the T allele was associated with higher fasting glucose and type 2 diabetes association estimates. This supports a T-allele-dose biomarker-tendency score.PubMed 19060907biomarker association - close proxyA companion MTNR1B fasting-glucose study reported strong association at the MTNR1B locus and highlighted rs10830963 as the strongest signal, while noting rs1387153 among exchanged MTNR1B signals. This supports treating rs1387153 as a nearby biomarker signal with modest certainty.

SLC2A23 SNPs - 3 claimsShow SNPs

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rs1219097421 claims - 2 study rows

transport activity - AA or compound-heterozygous SLC2A2 deficiency context

GLUT2 glucose transport activity tendency

Strong

rs121909742 A on the genomic plus strand / SLC2A2 c.1093C>T / p.Arg365Ter is associated with lower GLUT2 glucose transport activity tendency in recessive or compound-heterozygous Fanconi-Bickel contexts.

SLC2A2 rs121909742 A is staged as a recessive truncating GLUT2 allele affecting glucose and galactose transport biology.

Likely effectLower transport signal

Signal sizeModerate signal

Evidence supportStrong support

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ClinVar RCV000017472clinical curation - directClinVar maps rs121909742 to SLC2A2 c.1093C>T / p.Arg365Ter and classifies it as pathogenic for Fanconi-Bickel syndrome, with truncated GLUT2 context.PMCID PMC10921798clinical curation - directThe checked Fanconi-Bickel source supports SLC2A2/GLUT2 defects as impairing glucose transport with hepatic glycogen accumulation, fasting hypoglycemia, postprandial hyperglycemia, glucosuria, and renal tubular metabolic findings.

rs1219097431 claims - 2 study rows

transport activity - AA or compound-heterozygous SLC2A2 deficiency context

GLUT2 glucose transport activity tendency

Strong

rs121909743 A on the genomic plus strand / SLC2A2 p.Arg301Ter is associated with lower GLUT2 glucose transport activity tendency in recessive or compound-heterozygous Fanconi-Bickel contexts.

SLC2A2 rs121909743 A is staged as a recessive truncating GLUT2 allele affecting glucose and galactose transport biology.

Likely effectLower transport signal

Signal sizeModerate signal

Evidence supportStrong support

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ClinVar Variation 16093clinical curation - directClinVar maps rs121909743 to SLC2A2 c.901C>T / p.Arg301Ter and classifies it as pathogenic for Fanconi-Bickel syndrome.PMCID PMC10921798clinical curation - directThe checked Fanconi-Bickel source supports SLC2A2/GLUT2 defects as impairing glucose transport with hepatic glycogen accumulation, fasting hypoglycemia, postprandial hyperglycemia, glucosuria, and renal tubular metabolic findings.

rs54001 claims - 2 study rows

biomarker tendency - A / p.Thr110Ile

fasting glucose and HbA1c tendency

Moderate

rs5400 A at SLC2A2 is associated with lower fasting glucose and HbA1c tendency in large glycemic-trait association data.

SLC2A2 rs5400 A is staged as a glycemic biomarker-lowering GLUT2-locus signal.

Likely effectLower biomarker tendency

Signal sizeSmall signal

Evidence supportModerate support

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PMCID PMC11399760biomarker association - directThe checked large exome-array glycemic-trait source reports rs5400 A/G p.Thr110Ile with negative fasting glucose and HbA1c effects.PMCID PMC5007158biomarker association - close proxyThe checked source identifies nonsynonymous rs5400 in SLC2A2 as the main variant associated with glycemic traits such as fasting glucose and HbA1c.

FBP12 SNPs - 2 claimsShow SNPs

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rs1219181891 claims - 2 study rows

enzyme activity - TT or compound-heterozygous FBP1 deficiency context

Fructose-1,6-bisphosphatase activity tendency

Strong

rs121918189 T (forward-genomic; FBP1 c.530C>A / p.Ala177Asp transcript context) is associated with lower fructose-1,6-bisphosphatase activity tendency and impaired gluconeogenic capacity in recessive or compound-heterozygous contexts.

FBP1 rs121918189 T is staged as the forward-genomic recessive gluconeogenesis allele affecting fasting glucose, lactate, and metabolic-acidosis context.

Likely effectLower enzyme activity signal

Signal sizeModerate signal

Evidence supportStrong support

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ClinVar Variation 869clinical curation - directClinVar maps rs121918189 to FBP1 c.530C>A / p.Ala177Asp and classifies the allele as pathogenic for fructose-1,6-bisphosphatase deficiency.PMCID PMC5412439clinical curation - directThe checked FBPase deficiency source supports FBP1 as a key gluconeogenic enzyme converting fructose-1,6-bisphosphate to fructose-6-phosphate, with deficiency causing hypoglycemia and metabolic acidosis presentations.

rs7576531541 claims - 2 study rows

enzyme activity - insC/insC or compound-heterozygous FBP1 deficiency context

Fructose-1,6-bisphosphatase activity tendency

Strong

rs757653154 / FBP1 c.960_961insG / p.Ser321ValfsTer13 is associated with lower fructose-1,6-bisphosphatase activity tendency and impaired gluconeogenic capacity in recessive or compound-heterozygous contexts.

FBP1 rs757653154 is staged as a recessive gluconeogenesis allele affecting fasting glucose, lactate, and metabolic-acidosis context.

Likely effectLower enzyme activity signal

Signal sizeModerate signal

Evidence supportStrong support

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ClinVar Variation 867clinical curation - directClinVar maps rs757653154 to FBP1 NM_000507.4:c.960_961insG / p.Ser321fs and classifies it as pathogenic/likely pathogenic for fructose-1,6-bisphosphatase deficiency with multiple submitters and no conflicts.GeneReviews Fructose-1,6-Bisphosphatase Deficiencyclinical curation - directGeneReviews supports FBP1 deficiency as a gluconeogenesis disorder caused by biallelic FBP1 pathogenic variants, with fasting or fructose-triggered hypoglycemia and lactic acidosis as direct biochemical consequences.

G6PC12 SNPs - 2 claimsShow SNPs

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rs18011751 claims - 2 study rows

enzyme activity - TT or compound-heterozygous G6PC1 deficiency context

Glucose-6-phosphatase activity tendency

Strong

rs1801175 T / G6PC1 c.247C>T / p.Arg83Cys is associated with lower glucose-6-phosphatase activity and impaired hepatic glucose output in recessive or compound-heterozygous glycogen storage disease Ia contexts.

G6PC1 rs1801175 T is staged as a pathogenic glucose-6-phosphatase deficiency allele affecting fasting glucose output and lactate, triglyceride, and uric-acid biomarker context.

Likely effectLower enzyme activity signal

Signal sizeModerate signal

Evidence supportStrong support

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ClinVar Variation 11998clinical curation - directClinVar maps rs1801175 to G6PC1 c.247C>T / p.Arg83Cys and classifies it as pathogenic with multiple submitters and no conflicts for glycogen storage disease Ia contexts.ClinVar RCV000012778clinical curation - directThe variant-condition record links G6PC1 p.Arg83Cys to glucose-6-phosphatase deficiency type Ia, supporting the hepatic glucose-output target.

rs803564841 claims - 2 study rows

enzyme activity - TT or compound-heterozygous G6PC1 deficiency context

Glucose-6-phosphatase activity tendency

Strong

rs80356484 T / G6PC1 c.648G>T is associated with lower glucose-6-phosphatase activity tendency through a splice-affecting glycogen-storage-disease Ia allele in recessive or compound-heterozygous contexts.

G6PC1 rs80356484 T is staged as a recessive hepatic glucose-production allele affecting fasting glucose and lactate/triglyceride/uric-acid biomarker context.

Likely effectLower enzyme activity signal

Signal sizeModerate signal

Evidence supportStrong support

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ClinVar Variation 12003clinical curation - directClinVar maps rs80356484 to G6PC1 c.648G>T and classifies the allele as pathogenic for glycogen storage disease type Ia, with reported splice-impact context despite the synonymous coding annotation.PMCID PMC4289013clinical curation - directThe checked G6PC/GSDIa source supports glucose-6-phosphatase deficiency as impaired fasting glucose production with hepatic glycogen/fat accumulation and lactate, triglyceride, and uric-acid biomarker consequences.

IRS12 SNPs - 4 claimsShow SNPs

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rs18012781 claims - 2 study rows

biomarker tendency - A

insulin resistance biomarker tendency

Moderate

rs1801278 A / Arg972 carrier status is associated with higher insulin resistance biomarker tendency.

IRS1 rs1801278 A is staged as an insulin-resistance biomarker allele, not as a disease-risk-only claim.

Likely effectHigher biomarker tendency

Signal sizeSmall signal

Evidence supportStrong support

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PMCID PMC6167972biomarker association - directThe checked IRS1 source identifies rs1801278 G>A / Gly972Arg and reports that GA+AA genotypes and the A allele were enriched in insulin-resistant versus insulin-sensitive T2DM participants with higher HOMA-IR context.PMCID PMC9408134biomarker association - directThe second checked source links IRS1 Gly972Arg / rs1801278 to obesity and insulin-resistance measures in PCOS; staged as supporting biomarker evidence only.

rs75783263 claims - 12 study rows

expression - AA

IRS1 gene expression

Moderate

rs7578326 AA is associated with reduced IRS1 gene expression.

IRS1-near rs7578326 is scored as a lower IRS1 expression tendency for A-containing genotypes, with a stronger score for AA than AG.

Likely effectLower gene expression signal

Signal sizeModerate signal

Evidence supportLimited support

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data list rs7578326 as an A/G variant, supporting use of AA, AG, and GG genotype letters in this file.Evidence 2gwas - loose proxyGWAS Catalog association data report rs7578326-A near IRS1 for type 2 diabetes. This supports metabolic relevance but does not directly support an IRS1 expression direction, so the row is neutral for the exact expression claim.PMC3080658expression eqtl - directThe large type 2 diabetes association study includes rs7578326 at the IRS1 locus and reports the A allele with lower IRS1 adipose expression in an expression analysis. This supports a cautious lower-expression direction for A-containing genotypes.PubMed 33505025expression eqtl - directA functional regulatory-variant study highlighted rs7578326 as a type 2 diabetes GWAS lead SNP predicted to target IRS1, with regulatory evidence in liver-derived cells and expression quantitative trait evidence in liver and adipose tissues. This supports the IRS1 expression target but not a standalone disease prediction.

expression - AG

IRS1 gene expression

Not used for pathway scoring

rs7578326 AG is associated with reduced IRS1 gene expression.

IRS1-near rs7578326 is scored as a lower IRS1 expression tendency for A-containing genotypes, with a stronger score for AA than AG.

Likely effectLower gene expression signal

Signal sizeSmall signal

Evidence supportLimited support

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data list rs7578326 as an A/G variant, supporting use of AA, AG, and GG genotype letters in this file.Evidence 2gwas - loose proxyGWAS Catalog association data report rs7578326-A near IRS1 for type 2 diabetes. This supports metabolic relevance but does not directly support an IRS1 expression direction, so the row is neutral for the exact expression claim.PMC3080658expression eqtl - directThe large type 2 diabetes association study includes rs7578326 at the IRS1 locus and reports the A allele with lower IRS1 adipose expression in an expression analysis. This supports a cautious lower-expression direction for A-containing genotypes.PubMed 33505025expression eqtl - directA functional regulatory-variant study highlighted rs7578326 as a type 2 diabetes GWAS lead SNP predicted to target IRS1, with regulatory evidence in liver-derived cells and expression quantitative trait evidence in liver and adipose tissues. This supports the IRS1 expression target but not a standalone disease prediction.

expression - GG

IRS1 gene expression

Not used for pathway scoring

rs7578326 GG has no scored directional claim for IRS1 gene expression.

IRS1-near rs7578326 is scored as a lower IRS1 expression tendency for A-containing genotypes, with a stronger score for AA than AG.

Likely effectNo clear expression signal

Signal sizeMinimal signal

Evidence supportVery limited support

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data list rs7578326 as an A/G variant, supporting use of AA, AG, and GG genotype letters in this file.Evidence 2gwas - loose proxyGWAS Catalog association data report rs7578326-A near IRS1 for type 2 diabetes. This supports metabolic relevance but does not directly support an IRS1 expression direction, so the row is neutral for the exact expression claim.PMC3080658expression eqtl - directThe large type 2 diabetes association study includes rs7578326 at the IRS1 locus and reports the A allele with lower IRS1 adipose expression in an expression analysis. This supports a cautious lower-expression direction for A-containing genotypes.PubMed 33505025expression eqtl - directA functional regulatory-variant study highlighted rs7578326 as a type 2 diabetes GWAS lead SNP predicted to target IRS1, with regulatory evidence in liver-derived cells and expression quantitative trait evidence in liver and adipose tissues. This supports the IRS1 expression target but not a standalone disease prediction.

SLC22A12 SNPs - 2 claimsShow SNPs

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rs122083571 claims - 2 study rows

transport activity - T

OCT1 transport activity

Strong

rs12208357 T is associated with reduced SLC22A1/OCT1 transport activity.

SLC22A1 rs12208357 T is staged as a reduced OCT1 transport allele, mainly supported by metformin pharmacogenomic evidence.

Likely effectLower transport signal

Signal sizeModerate signal

Evidence supportStrong support

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PMCID PMC4035531functional assay - directThe checked PharmGKB summary states that rs12208357 is c.181C>T / p.Arg61Cys and that the variant results in loss of OCT1 protein function with reduced metformin uptake. This supports a negative transport-activity direction for the T allele.PMCID PMC5903234biomarker association - close proxyThe checked Brazilian metformin pharmacokinetic study genotyped SLC22A1 rs12208357 c.181C>T / R61C and retained rs12208357 as a covariate associated with metformin systemic exposure. The discussion cites prior evidence that this variant abolishes OCT1 activity and reduces hepatic metformin uptake.

rs341304951 claims - 1 study rows

transport activity - A

OCT1 transport activity

Strong

rs34130495 A / OCT1 Gly401Ser is associated with reduced SLC22A1/OCT1 transport activity.

SLC22A1 rs34130495 A is staged as an OCT1 reduced-function allele, mainly relevant to metformin and organic-cation uptake.

Likely effectLower transport signal

Signal sizeModerate signal

Evidence supportModerate support

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PMCID PMC4035531functional assay - directThe checked PharmGKB SLC22A1 summary lists rs34130495 / Gly401Ser among the extensively studied OCT1 variants and summarizes in vitro evidence that reduced-function OCT1 alleles, including Gly401Ser, reduce metformin uptake and alter AMPK-linked cellular response.

TCF7L21 SNPs - 3 claimsShow SNPs

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rs79031463 claims - 12 study rows

biomarker tendency - TT

TCF7L2 biomarker tendency

Strong

rs7903146 TT is associated with increased TCF7L2 biomarker tendency.

TCF7L2 rs7903146 is scored as a glycemic-response biomarker tendency for T-containing genotypes, with a stronger score for TT than CT.

Likely effectHigher biomarker tendency

Signal sizeModerate signal

Evidence supportStrong support

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data identify rs7903146 as a TCF7L2 intronic variant with common C and T alleles. This supports using CC, CT, and TT genotype letters for the simplified record.PubMed 25015099expression eqtl - loose proxyZhou et al. studied TCF7L2 in rodent and human pancreatic islets and reported that the rs7903146 risk T allele was associated with increased TCF7L2 expression, lower insulin content, and lower insulin secretion. This supports a positive biomarker-tendency score for T-containing genotypes, with stronger scoring for TT than CT.PubMed 32788279biomarker association - close proxyGalderisi et al. reported that the T risk allele at rs7903146 was associated with a reduced incretin effect in obese youth without diabetes, along with a higher 1-hour glucose peak and lower insulin secretion-related measures in the lower incretin-effect group. This supports a cautious glycemic-response tendency rather than a diagnosis.Evidence 4review - close proxyA large HuGE review and meta-analysis reported higher type 2 diabetes association estimates for rs7903146 TT and CT genotypes compared with CC across many studies. This supports allele-dose-aware scoring, while the record remains limited to biomarker tendency and not disease prediction.

biomarker tendency - CT

TCF7L2 biomarker tendency

Moderate

rs7903146 CT is associated with increased TCF7L2 biomarker tendency.

TCF7L2 rs7903146 is scored as a glycemic-response biomarker tendency for T-containing genotypes, with a stronger score for TT than CT.

Likely effectHigher biomarker tendency

Signal sizeSmall signal

Evidence supportStrong support

Report useIncluded in pathway scoring

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data identify rs7903146 as a TCF7L2 intronic variant with common C and T alleles. This supports using CC, CT, and TT genotype letters for the simplified record.PubMed 25015099expression eqtl - loose proxyZhou et al. studied TCF7L2 in rodent and human pancreatic islets and reported that the rs7903146 risk T allele was associated with increased TCF7L2 expression, lower insulin content, and lower insulin secretion. This supports a positive biomarker-tendency score for T-containing genotypes, with stronger scoring for TT than CT.PubMed 32788279biomarker association - close proxyGalderisi et al. reported that the T risk allele at rs7903146 was associated with a reduced incretin effect in obese youth without diabetes, along with a higher 1-hour glucose peak and lower insulin secretion-related measures in the lower incretin-effect group. This supports a cautious glycemic-response tendency rather than a diagnosis.Evidence 4review - close proxyA large HuGE review and meta-analysis reported higher type 2 diabetes association estimates for rs7903146 TT and CT genotypes compared with CC across many studies. This supports allele-dose-aware scoring, while the record remains limited to biomarker tendency and not disease prediction.

biomarker tendency - CC

TCF7L2 biomarker tendency

Not used for pathway scoring

rs7903146 CC has no scored directional claim for TCF7L2 biomarker tendency.

TCF7L2 rs7903146 is scored as a glycemic-response biomarker tendency for T-containing genotypes, with a stronger score for TT than CT.

Likely effectNo clear biomarker tendency

Signal sizeMinimal signal

Evidence supportVery limited support

Report useEvidence only, not scored

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data identify rs7903146 as a TCF7L2 intronic variant with common C and T alleles. This supports using CC, CT, and TT genotype letters for the simplified record.PubMed 25015099expression eqtl - loose proxyZhou et al. studied TCF7L2 in rodent and human pancreatic islets and reported that the rs7903146 risk T allele was associated with increased TCF7L2 expression, lower insulin content, and lower insulin secretion. This supports a positive biomarker-tendency score for T-containing genotypes, with stronger scoring for TT than CT.PubMed 32788279biomarker association - close proxyGalderisi et al. reported that the T risk allele at rs7903146 was associated with a reduced incretin effect in obese youth without diabetes, along with a higher 1-hour glucose peak and lower insulin secretion-related measures in the lower incretin-effect group. This supports a cautious glycemic-response tendency rather than a diagnosis.Evidence 4review - close proxyA large HuGE review and meta-analysis reported higher type 2 diabetes association estimates for rs7903146 TT and CT genotypes compared with CC across many studies. This supports allele-dose-aware scoring, while the record remains limited to biomarker tendency and not disease prediction.

ABCC81 SNPs - 1 claimsShow SNPs

Open gene page

rs7571101 claims - 1 study rows

biomarker tendency - A / 1369S

KATP closure and insulin secretion tendency

Moderate

rs757110 A, encoding ABCC8 p.A1369S, is associated with greater KATP-channel closure and insulin-secretion tendency.

ABCC8 rs757110 A / 1369S is staged as increased beta-cell KATP closure and insulin secretion tendency.

Likely effectHigher biomarker tendency

Signal sizeSmall signal

Evidence supportModerate support

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PMCID PMC5521864functional assay - directThe checked ABCC8 source links the A DNA allele to 1369S, reports KATP-channel closure biology, and supports increased fasting insulin with lower 2-hour glucose tendency.

AGL1 SNPs - 1 claimsShow SNPs

Open gene page

rs1139941341 claims - 2 study rows

enzyme activity - biallelic or compound-heterozygous AGL deletion context

Glycogen debranching enzyme activity tendency

Strong

rs113994134 / AGL c.4456del / p.Ser1486fs is associated with lower glycogen debranching enzyme activity and impaired glycogen breakdown in recessive or compound-heterozygous glycogen storage disease III contexts.

AGL rs113994134 is staged as a frameshift glycogen debranching enzyme deficiency allele affecting hepatic and muscle glycogen handling.

Likely effectLower enzyme activity signal

Signal sizeModerate signal

Evidence supportStrong support

Report useIncluded in pathway scoring

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ClinVar RCV000177731clinical curation - directClinVar maps rs113994134 to AGL c.4456del / p.Ser1486fs and classifies the glycogen storage disease type III record as pathogenic with multiple submitters and no conflicts.PMID 9412782clinical curation - directThe checked AGL literature source supports glycogen debranching enzyme deficiency as the direct biochemical basis for glycogen storage disease III.

ALDOB1 SNPs - 1 claimsShow SNPs

Open gene page

rs1182044291 claims - 2 study rows

enzyme activity - AA or compound-heterozygous ALDOB deficiency context

Aldolase B fructose-metabolism activity tendency

Strong

rs118204429 A on the genomic plus strand / ALDOB c.178C>T / p.Arg60Ter is associated with lower aldolase B activity and impaired fructose-1-phosphate handling in recessive or compound-heterozygous hereditary fructose intolerance contexts.

ALDOB rs118204429 A is staged as a truncating hereditary fructose intolerance allele affecting fructose metabolism.

Likely effectLower enzyme activity signal

Signal sizeModerate signal

Evidence supportStrong support

Report useIncluded in pathway scoring

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ClinVar Variation 472clinical curation - directClinVar maps rs118204429 to ALDOB c.178C>T / p.Arg60Ter, a nonsense variant classified pathogenic for hereditary fructose intolerance.PMCID PMC10969590clinical curation - directThe checked hereditary fructose intolerance guideline source supports aldolase B deficiency as causing fructose-1-phosphate accumulation and metabolic decompensation after fructose, sucrose, or sorbitol exposure.

ENPP11 SNPs - 1 claimsShow SNPs

Open gene page

rs10444981 claims - 2 study rows

biomarker tendency - A

insulin receptor signaling tendency

Moderate

rs1044498 A / Q121 is associated with lower insulin receptor signaling tendency.

ENPP1 rs1044498 A / Q121 is staged as a gain-of-inhibitory-function insulin signaling allele.

Likely effectLower biomarker tendency

Signal sizeSmall signal

Evidence supportStrong support

Report useIncluded in pathway scoring

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PMCID PMC3088669functional assay - directThe checked ENPP1 source reports that ENPP1 Q121 is a gain-of-function amino acid substitution with increased inhibitory activity on insulin receptor autophosphorylation and downstream insulin signaling in liver, muscle, and beta-cell models.PMCID PMC2646511biomarker association - directThe second checked source provides human insulin-resistance/metabolic context for ENPP1 K121Q; staged only as close support for insulin signaling tendency.

G6PC21 SNPs - 1 claimsShow SNPs

Open gene page

rs134316521 claims - 1 study rows

biomarker tendency - A

fasting glucose setpoint tendency

Moderate

rs13431652 A is associated with higher fasting glucose setpoint tendency and higher G6PC2 promoter activity.

G6PC2 rs13431652 A is staged as a functional fasting-glucose promoter allele.

Likely effectHigher biomarker tendency

Signal sizeSmall signal

Evidence supportModerate support

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PMCID PMC3279535functional assay - directThe checked G6PC2 source reports rs13431652 A is associated with higher fasting plasma glucose, increased NF-Y binding, and higher G6PC2 promoter activity relative to G.

GIPR1 SNPs - 1 claimsShow SNPs

Open gene page

rs18004371 claims - 1 study rows

biomarker tendency - A / 354Q

GIP receptor long-term response tendency

Moderate

rs1800437 A, encoding GIPR 354Q, is associated with reduced long-term GIP receptor responsiveness through altered receptor kinetics and internalization.

GIPR rs1800437 A / 354Q is staged as impaired long-term incretin receptor response despite acute signaling differences.

Likely effectLower biomarker tendency

Signal sizeSmall signal

Evidence supportModerate support

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PMCID PMC7317972functional assay - directThe checked functional GIPR source reports E354Q receptor kinetic and internalization changes leading to desensitization/down-regulation and impaired long-term GIP system response.

GLP1R1 SNPs - 1 claimsShow SNPs

Open gene page

rs69237611 claims - 1 study rows

biomarker tendency - A / 168Ser

GLP-1 stimulated beta-cell responsivity tendency

Moderate

rs6923761 A, encoding GLP1R Gly168Ser, is associated with lower GLP-1-stimulated beta-cell responsivity in clamp testing.

GLP1R rs6923761 A / 168Ser is staged as lower GLP-1-stimulated beta-cell response.

Likely effectLower biomarker tendency

Signal sizeSmall signal

Evidence supportModerate support

Report useIncluded in pathway scoring

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PMCID PMC2928367functional assay - directThe checked human clamp source reports lower beta-cell responsivity among minor-allele carriers during GLP-1 infusion.

GYS21 SNPs - 1 claimsShow SNPs

Open gene page

rs1219184191 claims - 3 study rows

enzyme activity - AA or compound-heterozygous GYS2 deficiency context

Hepatic glycogen synthase activity tendency

Strong

rs121918419 A on the genomic plus strand / GYS2 c.736C>T / p.Arg246Ter is associated with lower hepatic glycogen synthase activity and impaired liver glycogen synthesis in recessive or compound-heterozygous glycogen storage disease 0 contexts.

GYS2 rs121918419 A is staged as a truncating hepatic glycogen synthase deficiency allele affecting glucose-pathway buffering.

Likely effectLower enzyme activity signal

Signal sizeModerate signal

Evidence supportStrong support

Report useIncluded in pathway scoring

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ClinVar Variation 16049clinical curation - directClinVar maps rs121918419 to GYS2 c.736C>T / p.Arg246Ter and classifies it as pathogenic/likely pathogenic for hepatic glycogen synthase deficiency.PMID 9691087functional assay - directThe checked original hepatic glycogen synthase deficiency source supports GYS2 loss-of-function and severely impaired glycogen synthase activity in affected individuals.PMCID PMC10354582clinical curation - directThe checked glycogen storage disease source supports GYS2 deficiency as hepatic glycogen synthase deficiency with fasting hypoglycemia and abnormal postprandial metabolism.

KCNJ111 SNPs - 3 claimsShow SNPs

Open gene page

rs52193 claims - 9 study rows

transport activity - TT

KCNJ11 transport activity

Moderate

rs5219 TT is associated with increased KCNJ11 transport activity.

KCNJ11 rs5219 is scored as a cautious tendency toward higher K(ATP) channel activity for T-containing genotypes, strongest for TT.

Likely effectHigher transport signal

Signal sizeModerate signal

Evidence supportLimited support

Report useIncluded in pathway scoring

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data place rs5219 in KCNJ11, which encodes potassium inwardly rectifying channel subfamily J member 11. This simplified record scores the common C and T genotype set used in the cited KCNJ11 E23K literature.PMC2712777functional assay - directVillareal et al. studied the Kir6.2 E23K variant and reported that the variant increased K(ATP) channel activity, reduced ATP inhibition, increased open probability, and was associated with lower insulin secretory responses in glucose-tolerant adults. This supports a positive transport-activity tendency for T-containing genotypes, with stronger scoring for TT than CT.PMC6118367biomarker association - loose proxyChatterjee et al. treated T as the rs5219 diabetes-risk allele, but rs5219 was not a significant independent predictor of incident diabetes and did not modify the serum-potassium association. This is loose null context, not directional transport-activity evidence.

transport activity - CT

KCNJ11 transport activity

Not used for pathway scoring

rs5219 CT is associated with increased KCNJ11 transport activity.

KCNJ11 rs5219 is scored as a cautious tendency toward higher K(ATP) channel activity for T-containing genotypes, strongest for TT.

Likely effectHigher transport signal

Signal sizeSmall signal

Evidence supportLimited support

Report useEvidence only, not scored

Show study evidence

NCBI RefSNP recordidentity only - unknownNCBI RefSNP data place rs5219 in KCNJ11, which encodes potassium inwardly rectifying channel subfamily J member 11. This simplified record scores the common C and T genotype set used in the cited KCNJ11 E23K literature.PMC2712777functional assay - directVillareal et al. studied the Kir6.2 E23K variant and reported that the variant increased K(ATP) channel activity, reduced ATP inhibition, increased open probability, and was associated with lower insulin secretory responses in glucose-tolerant adults. This supports a positive transport-activity tendency for T-containing genotypes, with stronger scoring for TT than CT.PMC6118367biomarker association - loose proxyChatterjee et al. treated T as the rs5219 diabetes-risk allele, but rs5219 was not a significant independent predictor of incident diabetes and did not modify the serum-potassium association. This is loose null context, not directional transport-activity evidence.

transport activity - CC

KCNJ11 transport activity

Not used for pathway scoring

rs5219 CC has no scored directional claim for KCNJ11 transport activity.

KCNJ11 rs5219 is scored as a cautious tendency toward higher K(ATP) channel activity for T-containing genotypes, strongest for TT.

Likely effectNo clear transport signal

Signal sizeMinimal signal

Evidence supportVery limited support

Report useEvidence only, not scored

Show study evidence

NCBI RefSNP recordidentity only - unknownNCBI RefSNP data place rs5219 in KCNJ11, which encodes potassium inwardly rectifying channel subfamily J member 11. This simplified record scores the common C and T genotype set used in the cited KCNJ11 E23K literature.PMC2712777functional assay - directVillareal et al. studied the Kir6.2 E23K variant and reported that the variant increased K(ATP) channel activity, reduced ATP inhibition, increased open probability, and was associated with lower insulin secretory responses in glucose-tolerant adults. This supports a positive transport-activity tendency for T-containing genotypes, with stronger scoring for TT than CT.PMC6118367biomarker association - loose proxyChatterjee et al. treated T as the rs5219 diabetes-risk allele, but rs5219 was not a significant independent predictor of incident diabetes and did not modify the serum-potassium association. This is loose null context, not directional transport-activity evidence.

PGM11 SNPs - 1 claimsShow SNPs

Open gene page

rs3975154231 claims - 3 study rows

enzyme activity - TT or compound-heterozygous PGM1 deficiency context

Phosphoglucomutase activity tendency

Strong

rs397515423 T / PGM1 c.1507C>T / p.Arg503Ter is associated with lower phosphoglucomutase activity and impaired glucose-1-phosphate/glucose-6-phosphate interconversion in recessive or compound-heterozygous PGM1 deficiency contexts.

PGM1 rs397515423 T is staged as a truncating PGM1 deficiency allele affecting glucose-phosphate interconversion, glycogen handling, and glycosylation biomarkers.

Likely effectLower enzyme activity signal

Signal sizeModerate signal

Evidence supportStrong support

Report useIncluded in pathway scoring

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ClinVar Variation 39772clinical curation - directClinVar maps rs397515423 to PGM1 c.1507C>T / p.Arg503Ter and classifies it as pathogenic for PGM1-congenital disorder of glycosylation.PMCID PMC4373661functional assay - directThe checked functional PGM1 deficiency source reports markedly reduced residual phosphoglucomutase activity in affected cells, supporting direct enzyme-activity loss.PMCID PMC5802404clinical curation - directThe checked PGM1 deficiency source supports the combined glycogenosis and congenital disorder of glycosylation phenotype, with glucose/glycogen and transferrin glycosylation endpoints.

PYGL1 SNPs - 1 claimsShow SNPs

Open gene page

rs1139939731 claims - 3 study rows

enzyme activity - AA or compound-heterozygous PYGL deficiency context

Liver glycogen phosphorylase activity tendency

Strong

rs113993973 A on the genomic plus strand / PYGL c.280C>T / p.Arg94Ter is associated with lower liver glycogen phosphorylase activity and impaired hepatic glycogenolysis in recessive or compound-heterozygous glycogen storage disease VI contexts.

PYGL rs113993973 A is staged as a truncating liver glycogen phosphorylase deficiency allele affecting hepatic glucose output.

Likely effectLower enzyme activity signal

Signal sizeModerate signal

Evidence supportStrong support

Report useIncluded in pathway scoring

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ClinVar RCV000020502clinical curation - directClinVar maps rs113993973 to PYGL c.280C>T / p.Arg94Ter, classifies it as pathogenic for glycogen storage disease VI, and describes it as a premature stop expected to disrupt PYGL.ACMG GSD VI/IX Practice Resourceclinical curation - directThe checked practice resource supports PYGL deficiency as liver glycogen phosphorylase deficiency affecting hepatic glycogenolysis and glucose-homeostasis biomarkers.PMCID PMC8391619clinical curation - directThe checked GSD VI source supports PYGL-related liver glycogen phosphorylase deficiency with hepatic glycogen breakdown and metabolic biomarker relevance.

SLC2A11 SNPs - 1 claimsShow SNPs

Open gene page

rs7947292211 claims - 2 study rows

transport activity - T

GLUT1 glucose transport activity tendency

Strong

rs794729221 T / SLC2A1 c.724C>T p.Gln242Ter is associated with lower GLUT1 glucose transport activity tendency.

SLC2A1 rs794729221 T is staged as a rare truncating GLUT1 deficiency allele affecting glucose transport and brain-energy biomarkers.

Likely effectLower transport signal

Signal sizeLarge signal

Evidence supportStrong support

Report useIncluded in pathway scoring

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ClinVar Variation 202196clinical curation - directClinVar maps rs794729221 to SLC2A1 c.724C>T / p.Gln242Ter and classifies the variant as pathogenic.GeneReviews GLUT1 Deficiencyclinical curation - directGeneReviews supports GLUT1 deficiency as impaired SLC2A1-mediated glucose transfer across the blood-brain barrier with hypoglycorrhachia as a defining biochemical finding.

SLC30A81 SNPs - 3 claimsShow SNPs

Open gene page

rs132666343 claims - 9 study rows

transport activity - CC

SLC30A8 transport activity

Moderate

rs13266634 CC is associated with reduced SLC30A8 transport activity.

SLC30A8 rs13266634 is scored as a lower ZnT8 zinc-transport-activity tendency for C-containing genotypes, stronger for CC than CT.

Likely effectLower transport signal

Signal sizeModerate signal

Evidence supportModerate support

Report useIncluded in pathway scoring

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NCBI RefSNP recordidentity only - unknownNCBI RefSNP data place rs13266634 in SLC30A8 and annotate the common C to T coding change as an Arg-to-Trp ZnT8 protein change. This supports using CC, CT, and TT genotype letters for this simplified record.PubMed 19542200functional assay - directA ZnT8 functional study reported that the R325 form, encoded by the C allele in the NCBI transcript annotation, showed lower apparent zinc transport activity than the W325 form. This supports a cautious lower-transport-activity score for C-containing genotypes.PubMed 20167458biomarker association - loose proxyA meta-analysis of 27 study groups reported that rs13266634 C-allele carriers had higher type 2 diabetes association estimates. This supports treating the C allele as biologically relevant, while the record remains about transport tendency rather than diagnosis.

transport activity - CT

SLC30A8 transport activity

Not used for pathway scoring

rs13266634 CT is associated with reduced SLC30A8 transport activity.

SLC30A8 rs13266634 is scored as a lower ZnT8 zinc-transport-activity tendency for C-containing genotypes, stronger for CC than CT.

Likely effectLower transport signal

Signal sizeSmall signal

Evidence supportModerate support

Report useEvidence only, not scored

Show study evidence

NCBI RefSNP recordidentity only - unknownNCBI RefSNP data place rs13266634 in SLC30A8 and annotate the common C to T coding change as an Arg-to-Trp ZnT8 protein change. This supports using CC, CT, and TT genotype letters for this simplified record.PubMed 19542200functional assay - directA ZnT8 functional study reported that the R325 form, encoded by the C allele in the NCBI transcript annotation, showed lower apparent zinc transport activity than the W325 form. This supports a cautious lower-transport-activity score for C-containing genotypes.PubMed 20167458biomarker association - loose proxyA meta-analysis of 27 study groups reported that rs13266634 C-allele carriers had higher type 2 diabetes association estimates. This supports treating the C allele as biologically relevant, while the record remains about transport tendency rather than diagnosis.

transport activity - TT

SLC30A8 transport activity

Not used for pathway scoring

rs13266634 TT has no scored directional claim for SLC30A8 transport activity.

SLC30A8 rs13266634 is scored as a lower ZnT8 zinc-transport-activity tendency for C-containing genotypes, stronger for CC than CT.

Likely effectNo clear transport signal

Signal sizeMinimal signal

Evidence supportVery limited support

Report useEvidence only, not scored

Show study evidence

NCBI RefSNP recordidentity only - unknownNCBI RefSNP data place rs13266634 in SLC30A8 and annotate the common C to T coding change as an Arg-to-Trp ZnT8 protein change. This supports using CC, CT, and TT genotype letters for this simplified record.PubMed 19542200functional assay - directA ZnT8 functional study reported that the R325 form, encoded by the C allele in the NCBI transcript annotation, showed lower apparent zinc transport activity than the W325 form. This supports a cautious lower-transport-activity score for C-containing genotypes.PubMed 20167458biomarker association - loose proxyA meta-analysis of 27 study groups reported that rs13266634 C-allele carriers had higher type 2 diabetes association estimates. This supports treating the C allele as biologically relevant, while the record remains about transport tendency rather than diagnosis.

SLC37A41 SNPs - 1 claimsShow SNPs

Open gene page

rs803564911 claims - 2 study rows

transport activity - biallelic or compound-heterozygous SLC37A4 deletion context

Glucose-6-phosphate transporter activity tendency

Strong

rs80356491 / SLC37A4 c.1042_1043del / p.Leu348Valfs*53 is associated with lower glucose-6-phosphate transporter activity and glycogen storage disease Ib metabolic biomarker disruption in recessive or compound-heterozygous contexts.

SLC37A4 rs80356491 is staged as a frameshift glucose-6-phosphate transporter deficiency allele affecting fasting glucose output and lactate, triglyceride, uric-acid, and neutrophil metabolic context.

Likely effectLower transport signal

Signal sizeModerate signal

Evidence supportStrong support

Report useIncluded in pathway scoring

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ClinVar RCV000007336clinical curation - directClinVar maps rs80356491 to SLC37A4 c.1042_1043del / p.Leu348Valfs*53 and classifies the glucose-6-phosphate transport defect record as pathogenic with multiple submitters.PMCID PMC10540602clinical curation - directThe checked GSD Ib source supports homozygous SLC37A4 c.1042_1043del disease context and glucose-6-phosphate transport defect management.

SLC5A21 SNPs - 1 claimsShow SNPs

Open gene page

rs1219186211 claims - 2 study rows

transport activity - AA or compound-heterozygous SLC5A2 deficiency context

SGLT2 renal glucose reabsorption activity tendency

Strong

rs121918621 A / SLC5A2 c.1320G>A / p.Trp440Ter is associated with lower SGLT2 renal glucose reabsorption activity and higher urinary glucose excretion in familial renal glucosuria contexts.

SLC5A2 rs121918621 A is staged as a rare SGLT2 loss-of-function allele affecting renal glucose reabsorption and urinary glucose handling.

Likely effectLower transport signal

Signal sizeModerate signal

Evidence supportStrong support

Report useIncluded in pathway scoring

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ClinVar RCV000013767clinical curation - directClinVar maps rs121918621 to SLC5A2 c.1320G>A / p.Trp440Ter and classifies the familial renal glucosuria record as pathogenic, with literature support for homozygous nonsense SGLT2 disruption and marked glucosuria with normal blood glucose.PMID 14614622biomarker association - directThe checked SLC5A2 familial renal glucosuria study supports SLC5A2 mutations as responsible for recessive renal glucosuria through the sodium-glucose cotransporter SGLT2.

Glucose Regulation Pathway: Why Carb Response Varies So Much

What this pathway does

Why it matters

What creates pressure on this pathway

Validation markers to consider

Genes and SNPs connected to this pathway

What may run higher

What may work more slowly

What to check next

GCKR biomarker tendency

GCKR biomarker tendency

GCKR biomarker tendency

GCKR biomarker tendency

GCKR biomarker tendency

GCKR biomarker tendency

MTNR1B biomarker tendency

MTNR1B biomarker tendency

MTNR1B biomarker tendency

MTNR1B biomarker tendency

MTNR1B biomarker tendency

MTNR1B biomarker tendency

GLUT2 glucose transport activity tendency

GLUT2 glucose transport activity tendency

fasting glucose and HbA1c tendency

Fructose-1,6-bisphosphatase activity tendency

Fructose-1,6-bisphosphatase activity tendency

Glucose-6-phosphatase activity tendency

Glucose-6-phosphatase activity tendency

insulin resistance biomarker tendency

IRS1 gene expression

IRS1 gene expression

IRS1 gene expression

OCT1 transport activity

OCT1 transport activity

TCF7L2 biomarker tendency

TCF7L2 biomarker tendency

TCF7L2 biomarker tendency

KATP closure and insulin secretion tendency

Glycogen debranching enzyme activity tendency

Aldolase B fructose-metabolism activity tendency

insulin receptor signaling tendency

fasting glucose setpoint tendency

GIP receptor long-term response tendency

GLP-1 stimulated beta-cell responsivity tendency

Hepatic glycogen synthase activity tendency

KCNJ11 transport activity

KCNJ11 transport activity

KCNJ11 transport activity

Phosphoglucomutase activity tendency

Liver glycogen phosphorylase activity tendency

GLUT1 glucose transport activity tendency

SLC30A8 transport activity

SLC30A8 transport activity

SLC30A8 transport activity

Glucose-6-phosphate transporter activity tendency

SGLT2 renal glucose reabsorption activity tendency

Where DNA analysis helps

Example interpretation

What to do next

Related pages

IRS1

TCF7L2

Fatigue after eating carbs

Fasting insulin

Genetic test for weight loss Europe

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