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Primary topic: gluten celiac immune risk pathway

Gluten and Celiac Immune Risk Pathway: HLA Context Before Interpretation

This pathway is about celiac-compatible immune background, especially HLA-DQ antigen presentation. It is not a standalone gluten intolerance test.

What this pathway does

The pathway helps determine whether gluten peptides can be presented in an HLA-DQ context associated with celiac disease susceptibility.

Why it matters

It matters because HLA-DQ compatibility can guide what to rule out or validate, but a positive genetic background is common and does not diagnose celiac disease.

What creates pressure on this pathway

  • HLA-DQ2.5 or DQ8 tag evidence suggesting compatible antigen presentation
  • small-effect immune susceptibility markers that add weak context only

Validation markers to consider

  • tTG-IgA with total IgA
  • EMA or DGP context when clinically appropriate
  • formal HLA-DQ typing when a rule-out question matters

Genes and SNPs connected to this pathway

This is about whether your HLA and immune markers look compatible with celiac-type gluten immune recognition. It is not a gluten intolerance diagnosis.

Study rows support the SNP/gene claim. The pathway connection comes from the curated gene-to-pathway map.

What may run higher

Your DNA may carry more celiac-compatible immune background. This means gluten-related symptoms deserve proper clinical context, not self-diagnosis.

What may work more slowly

Your DNA does not show a strong celiac-compatible immune background in the checked markers. Symptoms can still have other causes.

What to check next

If symptoms fit, check celiac serology such as tTG-IgA with total IgA, consider DGP or EMA when appropriate, and review HLA-DQ typing with a clinician before changing gluten intake.

6mapped genes
7mapped SNPs
7SNP/gene claims
7report eligible
HLA-DQA12 SNPs - 2 claimsShow SNPsOpen gene page
rs21876681 claims - 4 study rows

disease trait - T

HLA-DQ2.5 celiac-compatible background

Strong

rs2187668 T tags HLA-DQ2.5, a celiac-compatible HLA background.

rs2187668 T is treated as HLA-DQ2.5 compatibility context, not as celiac diagnosis.

Likely effectHigher trait association
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
dbSNP rs2187668identity only - unknowndbSNP confirms rs2187668 identity in the HLA-DQA1/HLA-DQB1 region.Monsuur 2008 HLA-DQ tag SNP studyclinical curation - directThe primary tag-SNP study lists rs2187668 T as the positive predicting allele for HLA-DQ2.5, the main celiac-compatible HLA background.GWAS Catalog rs2187668 celiac associationgwas - close proxyGWAS Catalog provides curated celiac disease association support for rs2187668 in the HLA-DQA1/HLA-DQB1 region; this supports susceptibility context only.Anderson 2013 HLA-DQ tag SNP rule-out contextclinical curation - close proxyThis clinical tag-SNP application supports use of HLA-DQ tag SNPs for celiac-compatible background and emphasizes genetics is useful for compatibility/rule-out context, not standalone diagnosis.
rs74541081 claims - 3 study rows

disease trait - CT

HLA-DQ8 celiac-compatible background

Strong

rs7454108 CT indicates one plus-strand C allele, corresponding to HLA-DQ8 tag context in the checked sources.

rs7454108 CT is scored as HLA-DQ8 compatibility context, not as celiac diagnosis.

Likely effectHigher trait association
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
dbSNP rs7454108identity only - unknowndbSNP confirms rs7454108 identity; GRCh38 placement is T>C, so the study-strand DQ8 tag maps to plus-strand C.Monsuur 2008 HLA-DQ8 tag SNP studyclinical curation - directThe primary tag-SNP study lists rs7454108 as the DQ8 positive-predicting marker; harmonized plus-strand C is scored as celiac-compatible HLA-DQ8 context.Anderson 2013 HLA-DQ tag SNP contextclinical curation - close proxyThe clinical tag-SNP paper uses rs7454108 among HLA-DQ tags for celiac-associated backgrounds and stresses limited positive predictive value.
NCF21 SNPs - 1 claimsShow SNPsOpen gene page
rs178495021 claims - 3 study rows

disease trait - GT

Non-HLA NCF2 celiac susceptibility context

Moderate

rs17849502 GT carries one GWAS Catalog celiac disease risk T allele at the NCF2 immune locus.

NCF2 rs17849502 GT is scored as small non-HLA celiac susceptibility context.

Likely effectHigher trait association
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
dbSNP rs17849502identity only - unknowndbSNP confirms rs17849502 identity; identity evidence does not assign celiac direction.Ricano-Ponce 2019 celiac Immunochip meta-analysis NCF2 locusgwas - directGWAS Catalog reports rs17849502-T associated with celiac disease in the Ricano-Ponce Immunochip meta-analysis, with NCF2 listed as the author-reported gene.PubMed record for Ricano-Ponce 2019 celiac Immunochip meta-analysisgwas - directPubMed identifies the primary Ricano-Ponce 2019 European Journal of Human Genetics celiac Immunochip meta-analysis behind the GWAS Catalog rs17849502-T association.
PUS101 SNPs - 1 claimsShow SNPsOpen gene page
rs130034641 claims - 3 study rows

disease trait - AG

Non-HLA PUS10/REL celiac susceptibility context

Moderate

rs13003464 AG carries one GWAS Catalog celiac disease risk G allele at the PUS10/REL immune locus.

PUS10/REL rs13003464 AG is scored as small non-HLA celiac susceptibility context.

Likely effectHigher trait association
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
dbSNP rs13003464identity only - unknowndbSNP confirms rs13003464 identity; identity evidence does not assign celiac direction.Dubois 2010 celiac GWAS PUS10/REL locusgwas - directGWAS Catalog reports rs13003464-G associated with celiac disease at the PUS10/REL immune locus in the Dubois 2010 European celiac GWAS.Trynka 2011 dense celiac genotyping PUS10 locusgwas - directGWAS Catalog reports rs13003464-G associated with celiac disease in the Trynka dense genotyping study, with PUS10 listed as the author-reported gene.
SH2B31 SNPs - 1 claimsShow SNPsOpen gene page
rs31845041 claims - 3 study rows

disease trait - CT

Non-HLA SH2B3 celiac susceptibility context

Moderate

rs3184504 CT carries one GWAS Catalog celiac disease risk C allele at the SH2B3 immune-signaling locus.

SH2B3 rs3184504 CT is scored as small non-HLA celiac susceptibility context.

Likely effectHigher trait association
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
dbSNP rs3184504identity only - unknowndbSNP confirms rs3184504 identity; identity evidence does not assign celiac direction.Trynka 2011 dense celiac genotyping SH2B3 locusgwas - directGWAS Catalog reports rs3184504-C associated with celiac disease in the Trynka dense genotyping study, with SH2B3 and ATXN2 listed as author-reported genes.PubMed record for Trynka 2011 dense celiac genotypinggwas - directPubMed identifies the primary Trynka 2011 Nature Genetics dense genotyping study behind the GWAS Catalog rs3184504-C celiac association.
TNFAIP31 SNPs - 1 claimsShow SNPsOpen gene page
rs23278321 claims - 3 study rows

disease trait - AG

Non-HLA TNFAIP3 celiac susceptibility context

Moderate

rs2327832 AG carries one GWAS Catalog celiac disease risk G allele at the TNFAIP3 immune-regulation locus.

TNFAIP3 rs2327832 AG is scored as small non-HLA celiac susceptibility context.

Likely effectHigher trait association
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
dbSNP rs2327832identity only - unknowndbSNP confirms rs2327832 identity; identity evidence does not assign celiac direction.Dubois 2010 celiac GWAS TNFAIP3 locusgwas - directGWAS Catalog reports rs2327832-G associated with celiac disease, with TNFAIP3 as the author-reported gene in the Dubois 2010 celiac GWAS.PubMed record for Dubois 2010 celiac GWASgwas - directPubMed identifies the primary Dubois 2010 Nature Genetics celiac GWAS behind the GWAS Catalog rs2327832-G celiac association.
ZMIZ11 SNPs - 1 claimsShow SNPsOpen gene page
rs12505521 claims - 3 study rows

disease trait - AA

Non-HLA ZMIZ1 celiac susceptibility context

Moderate

rs1250552 AA carries the GWAS Catalog celiac disease risk A allele at the ZMIZ1 immune locus.

ZMIZ1 rs1250552 AA is scored as small non-HLA celiac susceptibility context.

Likely effectHigher trait association
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
dbSNP rs1250552identity only - unknowndbSNP confirms rs1250552 identity; identity evidence does not assign celiac direction.Trynka 2011 dense celiac genotyping ZMIZ1 locusgwas - directGWAS Catalog reports rs1250552-A associated with celiac disease in the Trynka dense genotyping study, with ZMIZ1 listed as the author-reported gene.PubMed record for Trynka 2011 dense celiac genotypinggwas - directPubMed identifies the primary Trynka 2011 Nature Genetics dense genotyping study behind the GWAS Catalog rs1250552-A celiac association.

Where DNA analysis helps

DNA helps decide whether gluten-related symptoms deserve celiac-focused clinical validation before diet changes obscure testing.

Example interpretation

A celiac-compatible HLA signal can make formal follow-up worth discussing when symptoms fit, but it does not prove gluten is the cause.

Suggested validation: tTG-IgA with total IgA while still eating gluten.

What to do next

  • do not start a long gluten-free trial before celiac testing if celiac disease is a real question
  • use symptoms and serology to decide whether the genetic background matters
  • treat non-HLA SNPs as weak context only

Related pages

HLA-DQA1

HLA-DQA1 celiac immune risk

HLA-DQB1

HLA-DQB1 celiac immune risk

Histamine intolerance

histamine intolerance genetics

hsCRP and inflammatory load

hsCRP and inflammatory load DNA follow-up

Can DNA predict metabolism?

can DNA predict metabolism

23andMe vs Metastate metabolism report

23andMe vs Metastate metabolism report

Get the full report

Use your DNA file to see which pathways may be worth validating first.