HLA-DQA1

Chr 6ARMulti

major histocompatibility complex, class II, DQ alpha 1

Also known as: CELIAC1, DQ-A1, DQA1, HLA-DQA, HLA-DQA1*

NCBI Gene: 3117ENSG00000196735UniProt: P01909

HLA-DQA1 belongs to the HLA class II alpha chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B Lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa. It is encoded by 5 exons; exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

{Celiac disease, susceptibility to}MIM #212750
ARMulti
22
ClinVar variants
5
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— HLA-DQA1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 4 VUS of 22 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.97LOEUF
pLI 0.024
Z-score 1.64
OE 0.42 (0.21–0.97)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.63Z-score
OE missense 0.60 (0.49–0.72)
77 obs / 129.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.42 (0.21–0.97)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.60 (0.49–0.72)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.72
0≤1.21.6
LoF obs/exp: 4 / 9.4Missense obs/exp: 77 / 129.1Syn Z: 1.53

ClinVar Variant Classifications

22 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS4
Likely Benign9
Benign4
4
Pathogenic
1
Likely Pathogenic
4
VUS
9
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
1
0
1
VUS
0
0
4
0
4
Likely Benign
0
3
3
3
9
Benign
0
2
2
0
4
Total0514322

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HLA-DQA1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Celiac disease, susceptibility to}

MIM #212750

Molecular basis of disorder known

Autosomal recessiveMultifactorial
📖
GeneReview available — HLA-DQA1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The HLA complex and coeliac disease.
Espino L et al.·Int Rev Cell Mol Biol
2021Review
Synovial cell cross-talk with cartilage plays a major role in the pathogenesis of osteoarthritis.
Chou CH et al.·Sci Rep
2020
MSU crystal deposition contributes to inflammation and immune responses in gout remission.
Gu H et al.·Cell Rep
2023
Genome-Wide Association Study in Acute Tubulointerstitial Nephritis.
Zhou XJ et al.·J Am Soc Nephrol
2023Meta-analysis
HLA-DQB1*05 subtypes and not DRB1*10:01 mediates risk in anti-IgLON5 disease.
Yogeshwar SM et al.·Brain
2024
Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome.
Barry A et al.·Nat Commun
2023Meta-analysis
Association Study Identified HLA-DQA1 as a Novel Genetic Risk of Systemic Lupus Erythematosus-Associated Pulmonary Arterial Hypertension.
Qian J et al.·Arthritis Rheumatol
2023
Mechanisms and management of loss of response to anti-TNF therapy for patients with Crohn's disease: 3-year data from the prospective, multicentre PANTS cohort study.
Chanchlani N et al.·Lancet Gastroenterol Hepatol
2024Cohort
A multi-ancestry genome-wide association study in type 1 diabetes.
Michalek DA et al.·Hum Mol Genet
2024
Genetics of keloid scarring.
Shih B et al.·Arch Dermatol Res
2010Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools