HLA-DOA

Chr 6

major histocompatibility complex, class II, DO alpha

NCBI Gene: 3111ENSG00000204252UniProt: P06340

Important modulator in the HLA class II restricted antigen presentation pathway by interaction with the HLA-DM molecule in B-cells. Modifies peptide exchange activity of HLA-DM

10
ClinVar variants
5
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HLA-DOA
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 2 VUS of 10 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.
1.85LOEUF
pLI 0.000
Z-score -0.81
OE 1.27 (0.82–1.85)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.47Z-score
OE missense 0.89 (0.78–1.03)
141 obs / 157.6 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.1.27 (0.82–1.85)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.78–1.03)
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.0.83
0≤1.21.6
LoF obs/exp: 13 / 10.2Missense obs/exp: 141 / 157.6Syn Z: 1.08

ClinVar Variant Classifications

10 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS2
Likely Benign1
Benign2
4
Pathogenic
1
Likely Pathogenic
2
VUS
1
Likely Benign
2
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
2
0
2
Likely Benign
0
0
1
0
1
Benign
0
0
0
2
2
Total008210

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

View in ClinVar →

Protein Context — Lollipop Plot

HLA-DOA · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Single cell transcriptomics reveals dysregulated immnue homeostasis in different stages in HPV-induced cutaneous squamous cell carcinoma.
Ding L et al.·Exp Dermatol
2024Case report
Contribution of a Non-classical HLA Gene, HLA-DOA, to the Risk of Rheumatoid Arthritis.
Okada Y et al.·Am J Hum Genet
2016
ALOX5AP suppresses osteosarcoma progression via Wnt/β-catenin/EMT pathway and associates with clinical prognosis and immune infiltration.
Han GD et al.·J Orthop Surg Res
2023
Identifying dynamic pathway interactions based on clinical information.
Kim S·Comput Biol Chem
2017
Identification of prognostic genes in adrenocortical carcinoma microenvironment based on bioinformatic methods.
Li X et al.·Cancer Med
2020
CD74, a novel predictor for bronchopulmonary dysplasia in preterm infants.
Gao J et al.·Medicine (Baltimore)
2020
DNA polymorphisms predict time to progression from uncomplicated to complicated Crohn's disease.
Pernat Drobež C et al.·Eur J Gastroenterol Hepatol
2018
m6A regulator-mediated RNA methylation modification patterns are involved in immune microenvironment regulation of periodontitis.
Zhang X et al.·J Cell Mol Med
2021
Enhanced B Cell Alloantigen Presentation and Its Epigenetic Dysregulation in Liver Transplant Rejection.
Ningappa M et al.·Am J Transplant
2016
An Unbiased Machine Learning Exploration Reveals Gene Sets Predictive of Allograft Tolerance After Kidney Transplantation.
Fu Q et al.·Front Immunol
2021
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