What this pathway does
The pathway influences caffeine clearance speed, receptor sensitivity, and how much stimulant load carries into sleep and recovery.
Why it matters
It matters because some people do not need a pathology explanation as much as they need a cleaner way to understand stimulant response.
What creates pressure on this pathway
- slower caffeine clearance that extends exposure
- higher receptor sensitivity that makes a normal dose feel stronger
Validation markers to consider
- response tracking
- sleep disruption pattern
- stimulant tolerance context
Genes and SNPs connected to this pathway
This is about how strongly your body reacts to caffeine and stimulant-like substances.
Study rows support the SNP/gene claim. The pathway connection comes from the curated gene-to-pathway map.
What may run higher
Coffee may hit hard: wired, shaky, anxious, or awake too long.
What may work more slowly
Coffee is less likely to bother you. You may need more to feel the same effect.
What to check next
Watch caffeine dose, timing, sleep latency, resting heart rate, anxiety, and blood-pressure response.
6mapped genes
10mapped SNPs
40SNP/gene claims
17report eligible
NAT22 SNPs - 13 claimsShow SNPs
Open gene pagers179993010 claims - 30 study rows
enzyme activity - AA
NAT2 enzyme activity
rs1799930 AA is associated with reduced NAT2 enzyme activity.
NAT2 rs1799930 is scored as a lower acetylation-enzyme activity tendency for A-containing genotypes, strongest for AA and intermediate for one A copy.
Likely effectLower enzyme activity signal
Signal sizeModerate signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs1799930 in NAT2 and annotates the common G>A change as NM_000015.3:c.590G>A, a missense change from arginine to glutamine in NAT2. The same record includes rarer C and T alleles, so those genotypes are handled conservatively.ClinVar recordclinical curation - directClinVar Variation ID 722 links rs1799930 with slow acetylator due to an N-acetyltransferase enzyme variant in a drug-response context. This supports lower NAT2 enzyme-activity tendency for A-containing genotypes while avoiding disease prediction.PMC3285565other - loose proxyA NAT2 acetylator-phenotype study includes rs1799930 in multi-SNP panels used to infer rapid, intermediate, and slow acetylator status and states that a four-SNP panel has high accuracy. This supports using rs1799930 as a meaningful but incomplete single-SNP activity tendency.
enzyme activity - AG
NAT2 enzyme activity
rs1799930 AG is associated with reduced NAT2 enzyme activity.
NAT2 rs1799930 is scored as a lower acetylation-enzyme activity tendency for A-containing genotypes, strongest for AA and intermediate for one A copy.
Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs1799930 in NAT2 and annotates the common G>A change as NM_000015.3:c.590G>A, a missense change from arginine to glutamine in NAT2. The same record includes rarer C and T alleles, so those genotypes are handled conservatively.ClinVar recordclinical curation - directClinVar Variation ID 722 links rs1799930 with slow acetylator due to an N-acetyltransferase enzyme variant in a drug-response context. This supports lower NAT2 enzyme-activity tendency for A-containing genotypes while avoiding disease prediction.PMC3285565other - loose proxyA NAT2 acetylator-phenotype study includes rs1799930 in multi-SNP panels used to infer rapid, intermediate, and slow acetylator status and states that a four-SNP panel has high accuracy. This supports using rs1799930 as a meaningful but incomplete single-SNP activity tendency.
enzyme activity - AC
NAT2 enzyme activity
rs1799930 AC is associated with reduced NAT2 enzyme activity.
NAT2 rs1799930 is scored as a lower acetylation-enzyme activity tendency for A-containing genotypes, strongest for AA and intermediate for one A copy.
Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportLimited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs1799930 in NAT2 and annotates the common G>A change as NM_000015.3:c.590G>A, a missense change from arginine to glutamine in NAT2. The same record includes rarer C and T alleles, so those genotypes are handled conservatively.ClinVar recordclinical curation - directClinVar Variation ID 722 links rs1799930 with slow acetylator due to an N-acetyltransferase enzyme variant in a drug-response context. This supports lower NAT2 enzyme-activity tendency for A-containing genotypes while avoiding disease prediction.PMC3285565other - loose proxyA NAT2 acetylator-phenotype study includes rs1799930 in multi-SNP panels used to infer rapid, intermediate, and slow acetylator status and states that a four-SNP panel has high accuracy. This supports using rs1799930 as a meaningful but incomplete single-SNP activity tendency.
enzyme activity - AT
NAT2 enzyme activity
rs1799930 AT is associated with reduced NAT2 enzyme activity.
NAT2 rs1799930 is scored as a lower acetylation-enzyme activity tendency for A-containing genotypes, strongest for AA and intermediate for one A copy.
Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportLimited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs1799930 in NAT2 and annotates the common G>A change as NM_000015.3:c.590G>A, a missense change from arginine to glutamine in NAT2. The same record includes rarer C and T alleles, so those genotypes are handled conservatively.ClinVar recordclinical curation - directClinVar Variation ID 722 links rs1799930 with slow acetylator due to an N-acetyltransferase enzyme variant in a drug-response context. This supports lower NAT2 enzyme-activity tendency for A-containing genotypes while avoiding disease prediction.PMC3285565other - loose proxyA NAT2 acetylator-phenotype study includes rs1799930 in multi-SNP panels used to infer rapid, intermediate, and slow acetylator status and states that a four-SNP panel has high accuracy. This supports using rs1799930 as a meaningful but incomplete single-SNP activity tendency.
enzyme activity - CC
NAT2 enzyme activity
rs1799930 CC has no scored directional claim for NAT2 enzyme activity.
NAT2 rs1799930 is scored as a lower acetylation-enzyme activity tendency for A-containing genotypes, strongest for AA and intermediate for one A copy.
Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs1799930 in NAT2 and annotates the common G>A change as NM_000015.3:c.590G>A, a missense change from arginine to glutamine in NAT2. The same record includes rarer C and T alleles, so those genotypes are handled conservatively.ClinVar recordclinical curation - directClinVar Variation ID 722 links rs1799930 with slow acetylator due to an N-acetyltransferase enzyme variant in a drug-response context. This supports lower NAT2 enzyme-activity tendency for A-containing genotypes while avoiding disease prediction.PMC3285565other - loose proxyA NAT2 acetylator-phenotype study includes rs1799930 in multi-SNP panels used to infer rapid, intermediate, and slow acetylator status and states that a four-SNP panel has high accuracy. This supports using rs1799930 as a meaningful but incomplete single-SNP activity tendency.
enzyme activity - CG
NAT2 enzyme activity
rs1799930 CG has no scored directional claim for NAT2 enzyme activity.
NAT2 rs1799930 is scored as a lower acetylation-enzyme activity tendency for A-containing genotypes, strongest for AA and intermediate for one A copy.
Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs1799930 in NAT2 and annotates the common G>A change as NM_000015.3:c.590G>A, a missense change from arginine to glutamine in NAT2. The same record includes rarer C and T alleles, so those genotypes are handled conservatively.ClinVar recordclinical curation - directClinVar Variation ID 722 links rs1799930 with slow acetylator due to an N-acetyltransferase enzyme variant in a drug-response context. This supports lower NAT2 enzyme-activity tendency for A-containing genotypes while avoiding disease prediction.PMC3285565other - loose proxyA NAT2 acetylator-phenotype study includes rs1799930 in multi-SNP panels used to infer rapid, intermediate, and slow acetylator status and states that a four-SNP panel has high accuracy. This supports using rs1799930 as a meaningful but incomplete single-SNP activity tendency.
enzyme activity - CT
NAT2 enzyme activity
rs1799930 CT has no scored directional claim for NAT2 enzyme activity.
NAT2 rs1799930 is scored as a lower acetylation-enzyme activity tendency for A-containing genotypes, strongest for AA and intermediate for one A copy.
Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs1799930 in NAT2 and annotates the common G>A change as NM_000015.3:c.590G>A, a missense change from arginine to glutamine in NAT2. The same record includes rarer C and T alleles, so those genotypes are handled conservatively.ClinVar recordclinical curation - directClinVar Variation ID 722 links rs1799930 with slow acetylator due to an N-acetyltransferase enzyme variant in a drug-response context. This supports lower NAT2 enzyme-activity tendency for A-containing genotypes while avoiding disease prediction.PMC3285565other - loose proxyA NAT2 acetylator-phenotype study includes rs1799930 in multi-SNP panels used to infer rapid, intermediate, and slow acetylator status and states that a four-SNP panel has high accuracy. This supports using rs1799930 as a meaningful but incomplete single-SNP activity tendency.
enzyme activity - GG
NAT2 enzyme activity
rs1799930 GG has no scored directional claim for NAT2 enzyme activity.
NAT2 rs1799930 is scored as a lower acetylation-enzyme activity tendency for A-containing genotypes, strongest for AA and intermediate for one A copy.
Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs1799930 in NAT2 and annotates the common G>A change as NM_000015.3:c.590G>A, a missense change from arginine to glutamine in NAT2. The same record includes rarer C and T alleles, so those genotypes are handled conservatively.ClinVar recordclinical curation - directClinVar Variation ID 722 links rs1799930 with slow acetylator due to an N-acetyltransferase enzyme variant in a drug-response context. This supports lower NAT2 enzyme-activity tendency for A-containing genotypes while avoiding disease prediction.PMC3285565other - loose proxyA NAT2 acetylator-phenotype study includes rs1799930 in multi-SNP panels used to infer rapid, intermediate, and slow acetylator status and states that a four-SNP panel has high accuracy. This supports using rs1799930 as a meaningful but incomplete single-SNP activity tendency.
enzyme activity - GT
NAT2 enzyme activity
rs1799930 GT has no scored directional claim for NAT2 enzyme activity.
NAT2 rs1799930 is scored as a lower acetylation-enzyme activity tendency for A-containing genotypes, strongest for AA and intermediate for one A copy.
Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs1799930 in NAT2 and annotates the common G>A change as NM_000015.3:c.590G>A, a missense change from arginine to glutamine in NAT2. The same record includes rarer C and T alleles, so those genotypes are handled conservatively.ClinVar recordclinical curation - directClinVar Variation ID 722 links rs1799930 with slow acetylator due to an N-acetyltransferase enzyme variant in a drug-response context. This supports lower NAT2 enzyme-activity tendency for A-containing genotypes while avoiding disease prediction.PMC3285565other - loose proxyA NAT2 acetylator-phenotype study includes rs1799930 in multi-SNP panels used to infer rapid, intermediate, and slow acetylator status and states that a four-SNP panel has high accuracy. This supports using rs1799930 as a meaningful but incomplete single-SNP activity tendency.
enzyme activity - TT
NAT2 enzyme activity
rs1799930 TT has no scored directional claim for NAT2 enzyme activity.
NAT2 rs1799930 is scored as a lower acetylation-enzyme activity tendency for A-containing genotypes, strongest for AA and intermediate for one A copy.
Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs1799930 in NAT2 and annotates the common G>A change as NM_000015.3:c.590G>A, a missense change from arginine to glutamine in NAT2. The same record includes rarer C and T alleles, so those genotypes are handled conservatively.ClinVar recordclinical curation - directClinVar Variation ID 722 links rs1799930 with slow acetylator due to an N-acetyltransferase enzyme variant in a drug-response context. This supports lower NAT2 enzyme-activity tendency for A-containing genotypes while avoiding disease prediction.PMC3285565other - loose proxyA NAT2 acetylator-phenotype study includes rs1799930 in multi-SNP panels used to infer rapid, intermediate, and slow acetylator status and states that a four-SNP panel has high accuracy. This supports using rs1799930 as a meaningful but incomplete single-SNP activity tendency.
rs17999313 claims - 9 study rows
enzyme activity - AA
NAT2 enzyme activity
rs1799931 AA is associated with reduced NAT2 enzyme activity.
NAT2 rs1799931 is scored as a lower NAT2 acetylation-activity tendency when the A allele is present, strongest for AA and intermediate for AG.
Likely effectLower enzyme activity signal
Signal sizeModerate signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs1799931 in NAT2 and annotates the common A allele as NM_000015.3:c.857G>A, a Gly286Glu missense change. This supports scoring A-containing genotypes as the coding-change genotypes for this simplified record.PubMed 37592049functional assay - directA functional NAT2 study describes rs1799931 G857A as the signature change in NAT2*7B and reports substrate-dependent reduction of NAT2-catalyzed O-acetylation for some tested heterocyclic amine metabolites. This supports a lower NAT2 activity tendency for A-containing genotypes, with a stronger score for AA than AG.PMC3285565other - loose proxyA NAT2 phenotype-panel study used rs1799931 together with other NAT2 SNPs to infer rapid, intermediate, and slow acetylator phenotypes. This supports treating rs1799931 as informative for NAT2 activity, while limiting certainty because NAT2 acetylator status is usually haplotype-based rather than determined by this SNP alone.
enzyme activity - AG
NAT2 enzyme activity
rs1799931 AG is associated with reduced NAT2 enzyme activity.
NAT2 rs1799931 is scored as a lower NAT2 acetylation-activity tendency when the A allele is present, strongest for AA and intermediate for AG.
Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs1799931 in NAT2 and annotates the common A allele as NM_000015.3:c.857G>A, a Gly286Glu missense change. This supports scoring A-containing genotypes as the coding-change genotypes for this simplified record.PubMed 37592049functional assay - directA functional NAT2 study describes rs1799931 G857A as the signature change in NAT2*7B and reports substrate-dependent reduction of NAT2-catalyzed O-acetylation for some tested heterocyclic amine metabolites. This supports a lower NAT2 activity tendency for A-containing genotypes, with a stronger score for AA than AG.PMC3285565other - loose proxyA NAT2 phenotype-panel study used rs1799931 together with other NAT2 SNPs to infer rapid, intermediate, and slow acetylator phenotypes. This supports treating rs1799931 as informative for NAT2 activity, while limiting certainty because NAT2 acetylator status is usually haplotype-based rather than determined by this SNP alone.
enzyme activity - GG
NAT2 enzyme activity
rs1799931 GG has no scored directional claim for NAT2 enzyme activity.
NAT2 rs1799931 is scored as a lower NAT2 acetylation-activity tendency when the A allele is present, strongest for AA and intermediate for AG.
Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs1799931 in NAT2 and annotates the common A allele as NM_000015.3:c.857G>A, a Gly286Glu missense change. This supports scoring A-containing genotypes as the coding-change genotypes for this simplified record.PubMed 37592049functional assay - directA functional NAT2 study describes rs1799931 G857A as the signature change in NAT2*7B and reports substrate-dependent reduction of NAT2-catalyzed O-acetylation for some tested heterocyclic amine metabolites. This supports a lower NAT2 activity tendency for A-containing genotypes, with a stronger score for AA than AG.PMC3285565other - loose proxyA NAT2 phenotype-panel study used rs1799931 together with other NAT2 SNPs to infer rapid, intermediate, and slow acetylator phenotypes. This supports treating rs1799931 as informative for NAT2 activity, while limiting certainty because NAT2 acetylator status is usually haplotype-based rather than determined by this SNP alone.
UGT1A12 SNPs - 6 claimsShow SNPs
Open gene pagers81753473 claims - 9 study rows
enzyme activity - 77
UGT1A1 enzyme activity
rs8175347 77 is associated with reduced UGT1A1 enzyme activity.
UGT1A1 rs8175347 is scored as lower UGT1A1 activity when the 7-repeat allele is present, with the strongest score for 77.
Likely effectLower enzyme activity signal
Signal sizeModerate signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
PubMed 25394086clinical curation - close proxyThe PubMed abstract for this clinical study describes UGT1A1*28 rs8175347 as a promoter TA-repeat polymorphism. It states that 6 TA repeats correspond to normal UGT1A1 activity, while 7 repeats in one or two copies are associated with lower activity and can contribute to higher indirect bilirubin or altered handling of drugs metabolized by UGT1A1.PMC3938665biomarker association - loose proxyA study in healthy North-Europeans found that UGT1A1 rs8175347 TA-repeat genotypes were closely related to bilirubin concentration. The paper reports that TA7/TA7 diplotypes had higher bilirubin than other diplotypes and concludes that the TA7 allele was the predominant UGT1A1 variant responsible for increased bilirubin in that population.PubMed 34866848biomarker association - loose proxyThis PubMed record describes UGT1A1*28 as the 7TA allele in the UGT1A1 promoter and states that the additional TA repeat leads to a significant decrease in liver UGT-1A enzymatic activity and glucuronidation. The abstract also cautions that symptoms and bilirubin alone do not make a definitive Gilbert syndrome diagnosis.
enzyme activity - 67
UGT1A1 enzyme activity
rs8175347 67 is associated with reduced UGT1A1 enzyme activity.
UGT1A1 rs8175347 is scored as lower UGT1A1 activity when the 7-repeat allele is present, with the strongest score for 77.
Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
PubMed 25394086clinical curation - close proxyThe PubMed abstract for this clinical study describes UGT1A1*28 rs8175347 as a promoter TA-repeat polymorphism. It states that 6 TA repeats correspond to normal UGT1A1 activity, while 7 repeats in one or two copies are associated with lower activity and can contribute to higher indirect bilirubin or altered handling of drugs metabolized by UGT1A1.PMC3938665biomarker association - loose proxyA study in healthy North-Europeans found that UGT1A1 rs8175347 TA-repeat genotypes were closely related to bilirubin concentration. The paper reports that TA7/TA7 diplotypes had higher bilirubin than other diplotypes and concludes that the TA7 allele was the predominant UGT1A1 variant responsible for increased bilirubin in that population.PubMed 34866848biomarker association - loose proxyThis PubMed record describes UGT1A1*28 as the 7TA allele in the UGT1A1 promoter and states that the additional TA repeat leads to a significant decrease in liver UGT-1A enzymatic activity and glucuronidation. The abstract also cautions that symptoms and bilirubin alone do not make a definitive Gilbert syndrome diagnosis.
enzyme activity - 66
UGT1A1 enzyme activity
rs8175347 66 has no scored directional claim for UGT1A1 enzyme activity.
UGT1A1 rs8175347 is scored as lower UGT1A1 activity when the 7-repeat allele is present, with the strongest score for 77.
Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
PubMed 25394086clinical curation - close proxyThe PubMed abstract for this clinical study describes UGT1A1*28 rs8175347 as a promoter TA-repeat polymorphism. It states that 6 TA repeats correspond to normal UGT1A1 activity, while 7 repeats in one or two copies are associated with lower activity and can contribute to higher indirect bilirubin or altered handling of drugs metabolized by UGT1A1.PMC3938665biomarker association - loose proxyA study in healthy North-Europeans found that UGT1A1 rs8175347 TA-repeat genotypes were closely related to bilirubin concentration. The paper reports that TA7/TA7 diplotypes had higher bilirubin than other diplotypes and concludes that the TA7 allele was the predominant UGT1A1 variant responsible for increased bilirubin in that population.PubMed 34866848biomarker association - loose proxyThis PubMed record describes UGT1A1*28 as the 7TA allele in the UGT1A1 promoter and states that the additional TA repeat leads to a significant decrease in liver UGT-1A enzymatic activity and glucuronidation. The abstract also cautions that symptoms and bilirubin alone do not make a definitive Gilbert syndrome diagnosis.
rs8878293 claims - 9 study rows
biomarker tendency - TT
UGT1A1 biomarker tendency
rs887829 TT is associated with increased UGT1A1 biomarker tendency.
UGT1A1-region rs887829 is scored as a higher bilirubin tendency when the T allele is present, with a stronger score for TT than CT.
Likely effectHigher biomarker tendency
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs887829 in the UGT1A gene region and annotates it upstream of UGT1A1, with C and T as the common allele labels in population datasets. This supports a UGT1A1-region biomarker-tendency record rather than a direct coding enzyme-change record.PMC3306855gwas - close proxyA genome-wide study in African Americans found that UGT1A1 was a major locus for serum total bilirubin. The strongest signal was rs887829, and the paper reports that each copy of the T allele was associated with higher serum bilirubin in both prior European evidence and the African American cohort.PMC10451688gwas - close proxyA Danish child and adolescent GWAS reported rs887829 as the most significant bilirubin-associated SNP in its analysis and notes that this marker is located in the UGT1A1*28 locus, which has been strongly and positively associated with circulating bilirubin in adults.
biomarker tendency - CT
UGT1A1 biomarker tendency
rs887829 CT is associated with increased UGT1A1 biomarker tendency.
UGT1A1-region rs887829 is scored as a higher bilirubin tendency when the T allele is present, with a stronger score for TT than CT.
Likely effectHigher biomarker tendency
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs887829 in the UGT1A gene region and annotates it upstream of UGT1A1, with C and T as the common allele labels in population datasets. This supports a UGT1A1-region biomarker-tendency record rather than a direct coding enzyme-change record.PMC3306855gwas - close proxyA genome-wide study in African Americans found that UGT1A1 was a major locus for serum total bilirubin. The strongest signal was rs887829, and the paper reports that each copy of the T allele was associated with higher serum bilirubin in both prior European evidence and the African American cohort.PMC10451688gwas - close proxyA Danish child and adolescent GWAS reported rs887829 as the most significant bilirubin-associated SNP in its analysis and notes that this marker is located in the UGT1A1*28 locus, which has been strongly and positively associated with circulating bilirubin in adults.
biomarker tendency - CC
UGT1A1 biomarker tendency
rs887829 CC has no scored directional claim for UGT1A1 biomarker tendency.
UGT1A1-region rs887829 is scored as a higher bilirubin tendency when the T allele is present, 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
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs887829 in the UGT1A gene region and annotates it upstream of UGT1A1, with C and T as the common allele labels in population datasets. This supports a UGT1A1-region biomarker-tendency record rather than a direct coding enzyme-change record.PMC3306855gwas - close proxyA genome-wide study in African Americans found that UGT1A1 was a major locus for serum total bilirubin. The strongest signal was rs887829, and the paper reports that each copy of the T allele was associated with higher serum bilirubin in both prior European evidence and the African American cohort.PMC10451688gwas - close proxyA Danish child and adolescent GWAS reported rs887829 as the most significant bilirubin-associated SNP in its analysis and notes that this marker is located in the UGT1A1*28 locus, which has been strongly and positively associated with circulating bilirubin in adults.
CYP1A22 SNPs - 9 claimsShow SNPs
Open gene pagers24708933 claims - 12 study rows
biomarker tendency - TT
CYP1A2-region caffeine clearance tendency
rs2470893 TT is associated with increased CYP1A2-region caffeine clearance tendency.
CYP1A1/CYP1A2-region rs2470893 is treated as a caffeine-intake and caffeine-clearance-linked promoter signal. T-containing genotypes are scored as a higher caffeine-clearance-linked tendency, with TT stronger than CT.
Likely effectHigher biomarker tendency
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP identifies rs2470893 as a variation record in the chromosome 15 CYP1A1/CYP1A2 region. The scored caffeine literature for this file uses the common C/T labels.Amin et al. 2012, PMID 21876539gwas - close proxyA coffee-drinking GWAS and replication study reported that the rs2470893 T allele in the CYP1A1/CYP1A2 region was consistently positively associated with coffee consumption. Higher genetically influenced consumption at this locus is interpreted as a close proxy for higher caffeine-clearance tendency.Cornelis et al. 2011, PMID 21490707gwas - close proxyA GWAS meta-analysis of habitual caffeine intake mapped rs2470893 to the bidirectional CYP1A1/CYP1A2 promoter region. The study noted that rs2470893 lies in an AHR response element linked to transcriptional activation of CYP1A1 and CYP1A2, and supplementary genotype means showed higher intake in T/T than C/C groups.Rasmussen et al. 2016, PMID 27509179biomarker association - directA caffeine-metabolism twin study reported that rs2470893 explained part of caffeine AUC variation. This supports rs2470893 as close to measured caffeine pharmacokinetics, while the genotype direction is anchored to the T-allele intake direction from the larger GWAS sources.
biomarker tendency - CT
CYP1A2-region caffeine clearance tendency
rs2470893 CT is associated with increased CYP1A2-region caffeine clearance tendency.
CYP1A1/CYP1A2-region rs2470893 is treated as a caffeine-intake and caffeine-clearance-linked promoter signal. T-containing genotypes are scored as a higher caffeine-clearance-linked tendency, with TT stronger than CT.
Likely effectHigher biomarker tendency
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP identifies rs2470893 as a variation record in the chromosome 15 CYP1A1/CYP1A2 region. The scored caffeine literature for this file uses the common C/T labels.Amin et al. 2012, PMID 21876539gwas - close proxyA coffee-drinking GWAS and replication study reported that the rs2470893 T allele in the CYP1A1/CYP1A2 region was consistently positively associated with coffee consumption. Higher genetically influenced consumption at this locus is interpreted as a close proxy for higher caffeine-clearance tendency.Cornelis et al. 2011, PMID 21490707gwas - close proxyA GWAS meta-analysis of habitual caffeine intake mapped rs2470893 to the bidirectional CYP1A1/CYP1A2 promoter region. The study noted that rs2470893 lies in an AHR response element linked to transcriptional activation of CYP1A1 and CYP1A2, and supplementary genotype means showed higher intake in T/T than C/C groups.Rasmussen et al. 2016, PMID 27509179biomarker association - directA caffeine-metabolism twin study reported that rs2470893 explained part of caffeine AUC variation. This supports rs2470893 as close to measured caffeine pharmacokinetics, while the genotype direction is anchored to the T-allele intake direction from the larger GWAS sources.
biomarker tendency - CC
CYP1A2-region caffeine clearance tendency
rs2470893 CC has no scored directional claim for CYP1A2-region caffeine clearance tendency.
CYP1A1/CYP1A2-region rs2470893 is treated as a caffeine-intake and caffeine-clearance-linked promoter signal. T-containing genotypes are scored as a higher caffeine-clearance-linked tendency, with TT stronger than CT.
Likely effectNo clear biomarker tendency
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP identifies rs2470893 as a variation record in the chromosome 15 CYP1A1/CYP1A2 region. The scored caffeine literature for this file uses the common C/T labels.Amin et al. 2012, PMID 21876539gwas - close proxyA coffee-drinking GWAS and replication study reported that the rs2470893 T allele in the CYP1A1/CYP1A2 region was positively associated with coffee consumption. This source supports T-containing genotypes rather than CC for the directional claim.Cornelis et al. 2011, PMID 21490707gwas - close proxyA GWAS meta-analysis of habitual caffeine intake mapped rs2470893 to the bidirectional CYP1A1/CYP1A2 promoter region and reported stronger caffeine intake in T/T than C/C genotype groups. This source supports T-containing genotypes rather than CC.Rasmussen et al. 2016, PMID 27509179biomarker association - directA caffeine-metabolism twin study reported that rs2470893 explained part of caffeine AUC variation, supporting this marker as close to measured caffeine pharmacokinetics. The abstract-level source does not assign a genotype direction for CC, so it is neutral for this exact claim.
rs7625516 claims - 18 study rows
enzyme activity - AA
CYP1A2 enzyme activity
rs762551 AA is associated with increased CYP1A2 enzyme activity.
For common A/C calls, rs762551 is scored as a CYP1A2 caffeine-metabolism tendency: AA has the strongest higher-activity tendency, AC is weaker and less certain, and CC is not scored as increased.
Likely effectHigher enzyme activity signal
Signal sizeSmall signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs762551 in CYP1A2 and lists A, C, and a rare G observation for this marker. The common A/C contrast is the source-supported comparison used for the scored genotypes.PubMed 36701157biomarker association - directA prospective cohort study described CYP1A2 as a major caffeine-detoxifying enzyme and analyzed rs762551 with AA classified as fast caffeine metabolism and AC or CC as slower caffeine metabolism. The kidney outcomes in that study are not used here as a disease prediction.PubMed 19636338biomarker association - loose proxyA pharmacogenetic study reported that the CYP1A2*1F genotype, marked by rs762551 -163A, was associated with lower dose-normalized olanzapine serum concentrations, consistent with higher CYP1A2-mediated metabolism in that drug context.
enzyme activity - AC
CYP1A2 enzyme activity
rs762551 AC is associated with increased CYP1A2 enzyme activity.
For common A/C calls, rs762551 is scored as a CYP1A2 caffeine-metabolism tendency: AA has the strongest higher-activity tendency, AC is weaker and less certain, and CC is not scored as increased.
Likely effectHigher enzyme activity signal
Signal sizeSmall signal
Evidence supportModerate support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs762551 in CYP1A2 and lists A, C, and a rare G observation for this marker. The common A/C contrast is the source-supported comparison used for the scored genotypes.PubMed 36701157biomarker association - directA prospective cohort study described CYP1A2 as a major caffeine-detoxifying enzyme and analyzed rs762551 with AA classified as fast caffeine metabolism and AC or CC as slower caffeine metabolism. The kidney outcomes in that study are not used here as a disease prediction.PubMed 19636338biomarker association - loose proxyA pharmacogenetic study reported that the CYP1A2*1F genotype, marked by rs762551 -163A, was associated with lower dose-normalized olanzapine serum concentrations, consistent with higher CYP1A2-mediated metabolism in that drug context.
enzyme activity - AG
CYP1A2 enzyme activity
rs762551 AG has no scored directional claim for CYP1A2 enzyme activity.
For common A/C calls, rs762551 is scored as a CYP1A2 caffeine-metabolism tendency: AA has the strongest higher-activity tendency, AC is weaker and less certain, and CC is not scored as increased.
Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs762551 in CYP1A2 and lists A, C, and a rare G observation for this marker. The common A/C contrast is the source-supported comparison used for the scored genotypes.PubMed 36701157biomarker association - directA prospective cohort study described CYP1A2 as a major caffeine-detoxifying enzyme and analyzed rs762551 with AA classified as fast caffeine metabolism and AC or CC as slower caffeine metabolism. The kidney outcomes in that study are not used here as a disease prediction.PubMed 19636338biomarker association - loose proxyA pharmacogenetic study reported that the CYP1A2*1F genotype, marked by rs762551 -163A, was associated with lower dose-normalized olanzapine serum concentrations, consistent with higher CYP1A2-mediated metabolism in that drug context.
enzyme activity - CC
CYP1A2 enzyme activity
rs762551 CC has no scored directional claim for CYP1A2 enzyme activity.
For common A/C calls, rs762551 is scored as a CYP1A2 caffeine-metabolism tendency: AA has the strongest higher-activity tendency, AC is weaker and less certain, and CC is not scored as increased.
Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs762551 in CYP1A2 and lists A, C, and a rare G observation for this marker. The common A/C contrast is the source-supported comparison used for the scored genotypes.PubMed 36701157biomarker association - directA prospective cohort study described CYP1A2 as a major caffeine-detoxifying enzyme and analyzed rs762551 with AA classified as fast caffeine metabolism and AC or CC as slower caffeine metabolism. The kidney outcomes in that study are not used here as a disease prediction.PubMed 19636338biomarker association - loose proxyA pharmacogenetic study reported that the CYP1A2*1F genotype, marked by rs762551 -163A, was associated with lower dose-normalized olanzapine serum concentrations, consistent with higher CYP1A2-mediated metabolism in that drug context.
enzyme activity - CG
CYP1A2 enzyme activity
rs762551 CG has no scored directional claim for CYP1A2 enzyme activity.
For common A/C calls, rs762551 is scored as a CYP1A2 caffeine-metabolism tendency: AA has the strongest higher-activity tendency, AC is weaker and less certain, and CC is not scored as increased.
Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs762551 in CYP1A2 and lists A, C, and a rare G observation for this marker. The common A/C contrast is the source-supported comparison used for the scored genotypes.PubMed 36701157biomarker association - directA prospective cohort study described CYP1A2 as a major caffeine-detoxifying enzyme and analyzed rs762551 with AA classified as fast caffeine metabolism and AC or CC as slower caffeine metabolism. The kidney outcomes in that study are not used here as a disease prediction.PubMed 19636338biomarker association - loose proxyA pharmacogenetic study reported that the CYP1A2*1F genotype, marked by rs762551 -163A, was associated with lower dose-normalized olanzapine serum concentrations, consistent with higher CYP1A2-mediated metabolism in that drug context.
enzyme activity - GG
CYP1A2 enzyme activity
rs762551 GG has no scored directional claim for CYP1A2 enzyme activity.
For common A/C calls, rs762551 is scored as a CYP1A2 caffeine-metabolism tendency: AA has the strongest higher-activity tendency, AC is weaker and less certain, and CC is not scored as increased.
Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs762551 in CYP1A2 and lists A, C, and a rare G observation for this marker. The common A/C contrast is the source-supported comparison used for the scored genotypes.PubMed 36701157biomarker association - directA prospective cohort study described CYP1A2 as a major caffeine-detoxifying enzyme and analyzed rs762551 with AA classified as fast caffeine metabolism and AC or CC as slower caffeine metabolism. The kidney outcomes in that study are not used here as a disease prediction.PubMed 19636338biomarker association - loose proxyA pharmacogenetic study reported that the CYP1A2*1F genotype, marked by rs762551 -163A, was associated with lower dose-normalized olanzapine serum concentrations, consistent with higher CYP1A2-mediated metabolism in that drug context.
ADORA2A2 SNPs - 6 claimsShow SNPs
Open gene pagers48224923 claims - 10 study rows
biomarker tendency - CC
ADORA2A caffeine-response sensitivity
rs4822492 CC is associated with increased ADORA2A caffeine-response sensitivity.
ADORA2A rs4822492 is scored as a receptor-context caffeine-response marker, with CC assigned a higher sensitivity tendency based on caffeine-induced anxiety and stimulant physiology evidence.
Likely effectHigher biomarker tendency
Signal sizeSmall signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP identifies rs4822492 as a variation record in the ADORA2A region. The scored caffeine-response literature for this file uses C/G genotype labels.Childs et al. 2008, PMID 18305461biomarker association - directA double-blind caffeine challenge study reported a significant association between caffeine-induced anxiety after 150 mg caffeine and ADORA2A rs4822492. The genotype plot and related summaries support CC as the higher-anxiety genotype, while the small sample and linked ADORA2A markers keep certainty moderate.Baggott et al. 2013, PMID 23420115biomarker association - close proxyA human methylxanthine challenge study genotyped ADORA2A rs4822492 and reported that CC participants had greater physiological response across active conditions, including elevated peak heart rate compared with CG and GG groups. This supports CC as a stimulant-response sensitivity marker, though the effect was not caffeine-specific in isolation.Erblang et al. 2019, Genes 10(12):1021biomarker association - close proxyA population study of ADORA2A variants, caffeine intake, and sleep reported that rs4822492 was part of a linked ADORA2A sleep/caffeine haplotype context. The results support rs4822492 as relevant to caffeine-related sleep response, but the CC direction is weaker and partly phenotype-dependent.
biomarker tendency - CG
ADORA2A caffeine-response sensitivity
rs4822492 CG has no scored directional claim for ADORA2A caffeine-response sensitivity.
ADORA2A rs4822492 is scored as a receptor-context caffeine-response marker, with CC assigned a higher sensitivity tendency based on caffeine-induced anxiety and stimulant physiology evidence.
Likely effectNo clear biomarker tendency
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP identifies rs4822492 as a variation record in the ADORA2A region. The scored caffeine-response literature for this file uses C/G genotype labels.Childs et al. 2008, PMID 18305461biomarker association - directA double-blind caffeine challenge study reported a significant association between caffeine-induced anxiety after 150 mg caffeine and ADORA2A rs4822492. The simplified scoring keeps CG neutral because the directional signal is curated for CC.Baggott et al. 2013, PMID 23420115biomarker association - close proxyA human methylxanthine challenge study reported greater physiological response for CC than CG or GG groups at rs4822492. The simplified scoring keeps CG neutral because the source supports CC as the higher-response genotype.
biomarker tendency - GG
ADORA2A caffeine-response sensitivity
rs4822492 GG has no scored directional claim for ADORA2A caffeine-response sensitivity.
ADORA2A rs4822492 is scored as a receptor-context caffeine-response marker, with CC assigned a higher sensitivity tendency based on caffeine-induced anxiety and stimulant physiology evidence.
Likely effectNo clear biomarker tendency
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP identifies rs4822492 as a variation record in the ADORA2A region. The scored caffeine-response literature for this file uses C/G genotype labels.Childs et al. 2008, PMID 18305461biomarker association - directA double-blind caffeine challenge study reported a significant association between caffeine-induced anxiety after 150 mg caffeine and ADORA2A rs4822492. The simplified scoring keeps GG neutral because the directional signal is curated for CC.Baggott et al. 2013, PMID 23420115biomarker association - close proxyA human methylxanthine challenge study reported greater physiological response for CC than CG or GG groups at rs4822492. The simplified scoring keeps GG neutral because the source supports CC as the higher-response genotype.
rs57518763 claims - 12 study rows
biomarker tendency - TT
ADORA2A biomarker tendency
rs5751876 TT is associated with increased ADORA2A biomarker tendency.
ADORA2A rs5751876 is scored as a caffeine-response sensitivity tendency, with TT assigned a higher sensitivity score and CC or CT left neutral in this simplified model.
Likely effectHigher biomarker tendency
Signal sizeSmall signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs5751876 in ADORA2A and lists C and T as the observed alleles on the preferred genomic placement. This supports the C/T genotype labels used here.PMC2745641biomarker association - close proxyA double-blind caffeine challenge study reported that ADORA2A rs5751876 was associated with self-reported anxiety after a moderate caffeine dose, with TT participants showing the highest anxiety response and CC participants the lowest in the full sample. The study also noted that other ADORA2A and DRD2 variants may contribute.PMC3055635biomarker association - loose proxyA larger caffeine-response study reported that caffeine's anxiogenic effect was larger in ADORA2A rs5751876 TT participants, especially among people who usually consumed little or no caffeine. This supports scoring TT as higher caffeine-response sensitivity while leaving CT unscored in this simplified file.PMC8322233review - close proxyA review of adenosine A2A receptor variants summarized rs5751876 TT as repeatedly linked to enhanced caffeine-induced anxiety and other caffeine-response differences. It also describes rs5751876 as a marker within a broader ADORA2A variant context rather than a standalone diagnostic result.
biomarker tendency - CC
ADORA2A biomarker tendency
rs5751876 CC has no scored directional claim for ADORA2A biomarker tendency.
ADORA2A rs5751876 is scored as a caffeine-response sensitivity tendency, with TT assigned a higher sensitivity score and CC or CT left neutral in this simplified model.
Likely effectNo clear biomarker tendency
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs5751876 in ADORA2A and lists C and T as the observed alleles on the preferred genomic placement. This supports the C/T genotype labels used here.PMC2745641biomarker association - close proxyA double-blind caffeine challenge study reported that ADORA2A rs5751876 was associated with self-reported anxiety after a moderate caffeine dose, with TT participants showing the highest anxiety response and CC participants the lowest in the full sample. The study also noted that other ADORA2A and DRD2 variants may contribute.PMC3055635biomarker association - loose proxyA larger caffeine-response study reported that caffeine's anxiogenic effect was larger in ADORA2A rs5751876 TT participants, especially among people who usually consumed little or no caffeine. This supports scoring TT as higher caffeine-response sensitivity while leaving CT unscored in this simplified file.PMC8322233review - close proxyA review of adenosine A2A receptor variants summarized rs5751876 TT as repeatedly linked to enhanced caffeine-induced anxiety and other caffeine-response differences. It also describes rs5751876 as a marker within a broader ADORA2A variant context rather than a standalone diagnostic result.
biomarker tendency - CT
ADORA2A biomarker tendency
rs5751876 CT has no scored directional claim for ADORA2A biomarker tendency.
ADORA2A rs5751876 is scored as a caffeine-response sensitivity tendency, with TT assigned a higher sensitivity score and CC or CT left neutral in this simplified model.
Likely effectNo clear biomarker tendency
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP places rs5751876 in ADORA2A and lists C and T as the observed alleles on the preferred genomic placement. This supports the C/T genotype labels used here.PMC2745641biomarker association - close proxyA double-blind caffeine challenge study reported that ADORA2A rs5751876 was associated with self-reported anxiety after a moderate caffeine dose, with TT participants showing the highest anxiety response and CC participants the lowest in the full sample. The study also noted that other ADORA2A and DRD2 variants may contribute.PMC3055635biomarker association - loose proxyA larger caffeine-response study reported that caffeine's anxiogenic effect was larger in ADORA2A rs5751876 TT participants, especially among people who usually consumed little or no caffeine. This supports scoring TT as higher caffeine-response sensitivity while leaving CT unscored in this simplified file.PMC8322233review - close proxyA review of adenosine A2A receptor variants summarized rs5751876 TT as repeatedly linked to enhanced caffeine-induced anxiety and other caffeine-response differences. It also describes rs5751876 as a marker within a broader ADORA2A variant context rather than a standalone diagnostic result.
COMT1 SNPs - 3 claimsShow SNPs
Open gene pagers46803 claims - 9 study rows
enzyme activity - AA
COMT enzyme activity
rs4680 AA is associated with reduced COMT enzyme activity.
COMT rs4680 is scored as a lower COMT enzyme-activity tendency for A-containing genotypes, strongest for AA and intermediate for AG.
Likely effectLower enzyme activity signal
Signal sizeModerate signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP data identify rs4680 in COMT as NM_000754.4:c.472G>A with a Val-to-Met protein substitution at residue 158 in the membrane-bound COMT transcript. The A allele corresponds to the Met form in these transcript annotations.PubMed 15457404functional assay - directChen et al. measured COMT mRNA, protein, and enzyme activity in postmortem human prefrontal cortex and reported that Val158Met, rs4680, significantly affected protein abundance and enzyme activity. Their results support lower COMT activity for A-containing genotypes, with AA lower than AG.Evidence 3clinical curation - loose proxyNCBI MedGen summarizes COMT activity variation as a codominant pattern: Met158 has lower thermostability and lower activity than Val158, and heterozygotes have intermediate activity. This supports the three-level genotype scoring used here.
enzyme activity - AG
COMT enzyme activity
rs4680 AG is associated with reduced COMT enzyme activity.
COMT rs4680 is scored as a lower COMT enzyme-activity tendency for A-containing genotypes, strongest for AA and intermediate for AG.
Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP data identify rs4680 in COMT as NM_000754.4:c.472G>A with a Val-to-Met protein substitution at residue 158 in the membrane-bound COMT transcript. The A allele corresponds to the Met form in these transcript annotations.PubMed 15457404functional assay - directChen et al. measured COMT mRNA, protein, and enzyme activity in postmortem human prefrontal cortex and reported that Val158Met, rs4680, significantly affected protein abundance and enzyme activity. Their results support lower COMT activity for A-containing genotypes, with AA lower than AG.Evidence 3clinical curation - loose proxyNCBI MedGen summarizes COMT activity variation as a codominant pattern: Met158 has lower thermostability and lower activity than Val158, and heterozygotes have intermediate activity. This supports the three-level genotype scoring used here.
enzyme activity - GG
COMT enzyme activity
rs4680 GG has no scored directional claim for COMT enzyme activity.
COMT rs4680 is scored as a lower COMT enzyme-activity tendency for A-containing genotypes, strongest for AA and intermediate for AG.
Likely effectNo clear enzyme signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP data identify rs4680 in COMT as NM_000754.4:c.472G>A with a Val-to-Met protein substitution at residue 158 in the membrane-bound COMT transcript. The A allele corresponds to the Met form in these transcript annotations.PubMed 15457404functional assay - directChen et al. measured COMT mRNA, protein, and enzyme activity in postmortem human prefrontal cortex and reported that Val158Met, rs4680, significantly affected protein abundance and enzyme activity. Their results support lower COMT activity for A-containing genotypes, with AA lower than AG.Evidence 3clinical curation - loose proxyNCBI MedGen summarizes COMT activity variation as a codominant pattern: Met158 has lower thermostability and lower activity than Val158, and heterozygotes have intermediate activity. This supports the three-level genotype scoring used here.
POR1 SNPs - 3 claimsShow SNPs
Open gene pagers176853 claims - 11 study rows
biomarker tendency - AA
POR-supported caffeine metabolism tendency
rs17685 AA is associated with increased POR-supported caffeine metabolism tendency.
POR rs17685 is scored as a caffeine-metabolism support marker. The A allele is associated with higher coffee consumption and POR-expression context, so A-containing genotypes are scored as a higher POR-supported caffeine-metabolism tendency.
Likely effectHigher biomarker tendency
Signal sizeSmall signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP identifies rs17685 as a variation record; the scored coffee and caffeine-metabolism literature for this file uses A/G genotype labels.Coffee and Caffeine Genetics Consortium 2015, PMID 25288136gwas - close proxyA large trans-ethnic GWAS meta-analysis identified rs17685 at the POR locus as a coffee-consumption signal. The paper described rs17685 as mapping to the POR 3-prime UTR, with the A variant associated with higher coffee consumption and linked to increased POR expression.Cornelis et al. 2016, PMID 27702941biomarker association - directA GWAS of plasma caffeine metabolites discussed rs17685 in POR as a coffee-consumption locus and noted that the C/G counterpart associated with lower coffee consumption was nominally associated with higher plasma caffeine levels. This supports the A-associated higher-consumption direction as compatible with faster clearance context.Systematic review 2024, PMC11515775review - close proxyA systematic review summarized POR rs17685 as a caffeine-metabolism-related locus and stated that the A variant is associated with larger caffeine intake and higher POR expression. This supports a cautious A-allele score as a supporting caffeine-metabolism tendency.
biomarker tendency - AG
POR-supported caffeine metabolism tendency
rs17685 AG is associated with increased POR-supported caffeine metabolism tendency.
POR rs17685 is scored as a caffeine-metabolism support marker. The A allele is associated with higher coffee consumption and POR-expression context, so A-containing genotypes are scored as a higher POR-supported caffeine-metabolism tendency.
Likely effectHigher biomarker tendency
Signal sizeSmall signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP identifies rs17685 as a variation record; the scored coffee and caffeine-metabolism literature for this file uses A/G genotype labels.Coffee and Caffeine Genetics Consortium 2015, PMID 25288136gwas - close proxyA large trans-ethnic GWAS meta-analysis identified rs17685 at the POR locus as a coffee-consumption signal. The paper described rs17685 as mapping to the POR 3-prime UTR, with the A variant associated with higher coffee consumption and linked to increased POR expression.Cornelis et al. 2016, PMID 27702941biomarker association - directA GWAS of plasma caffeine metabolites discussed rs17685 in POR as a coffee-consumption locus and noted that the C/G counterpart associated with lower coffee consumption was nominally associated with higher plasma caffeine levels. This supports the A-associated higher-consumption direction as compatible with faster clearance context.Systematic review 2024, PMC11515775review - close proxyA systematic review summarized POR rs17685 as a caffeine-metabolism-related locus and stated that the A variant is associated with larger caffeine intake and higher POR expression. This supports a cautious A-allele score as a supporting caffeine-metabolism tendency.
biomarker tendency - GG
POR-supported caffeine metabolism tendency
rs17685 GG has no scored directional claim for POR-supported caffeine metabolism tendency.
POR rs17685 is scored as a caffeine-metabolism support marker. The A allele is associated with higher coffee consumption and POR-expression context, so A-containing genotypes are scored as a higher POR-supported caffeine-metabolism tendency.
Likely effectNo clear biomarker tendency
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only - unknownNCBI RefSNP identifies rs17685 as a variation record; the scored coffee and caffeine-metabolism literature for this file uses A/G genotype labels.Coffee and Caffeine Genetics Consortium 2015, PMID 25288136gwas - close proxyA large trans-ethnic GWAS meta-analysis identified rs17685 at the POR locus as a coffee-consumption signal, with the A variant associated with higher coffee consumption and linked to increased POR expression. This source supports A-containing genotypes rather than GG for the directional claim.Cornelis et al. 2016, PMID 27702941biomarker association - directA GWAS of plasma caffeine metabolites discussed rs17685 in POR as a coffee-consumption locus and noted that the lower-consumption counterpart was nominally associated with higher plasma caffeine levels. This source supports A-containing genotypes rather than GG for the directional claim.
Where DNA analysis helps
DNA helps explain why the same stimulant pattern can feel manageable for one person and disruptive for another.
Example interpretation
Caffeine sensitivity may deserve attention when slower clearance and stronger response look like the real reason sleep and focus are unstable.
Suggested validation: caffeine response and sleep tracking.
What to do next
- use response and sleep tracking before turning stimulant sensitivity into a larger metabolic story
- review CYP1A2 and ADORA2A together to separate clearance from sensitivity