HLA-DMA

Chr 6

major histocompatibility complex, class II, DM alpha

Also known as: D6S222E, DMA, HLADM, RING6

NCBI Gene: 3108ENSG00000204257UniProt: P28067

HLA-DMA belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DMA) and a beta chain (DMB), both anchored in the membrane. It is located in intracellular vesicles. DM plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and the cytoplasmic tail. [provided by RefSeq, Jul 2008]

9
ClinVar variants
5
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HLA-DMA
⚡
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 9 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.
0.98LOEUF
pLI 0.002
Z-score 1.61
OE 0.50 (0.27–0.98)
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.
0.88Z-score
OE missense 0.80 (0.68–0.93)
116 obs / 145.9 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.0.50 (0.27–0.98)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.68–0.93)
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.0.92
0≤1.21.6
LoF obs/exp: 6 / 12.0Missense obs/exp: 116 / 145.9Syn Z: 0.49

ClinVar Variant Classifications

9 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS2
Likely Benign1
Benign1
4
Pathogenic
1
Likely Pathogenic
2
VUS
1
Likely Benign
1
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
0
1
1
Benign
0
0
0
1
1
Total00729

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

View in ClinVar →

Protein Context — Lollipop Plot

HLA-DMA · 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
Prognostic gene HLA-DMA associated with cell cycle and immune infiltrates in LUAD.
Huang YJ et al.·Clin Respir J
2023
Germline genetic biomarkers to stratify patients for personalized radiation treatment.
Deichaite I et al.·J Transl Med
2022Cohort
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
Expression of NOTCH1, NOTCH4, HLA-DMA and HLA-DRA is synergistically associated with T cell exclusion, immune checkpoint blockade efficacy and recurrence risk in ER-negative breast cancer.
Liu D et al.·Cell Oncol (Dordr)
2022
Identification of immune-related cervical cancer prognostic biomarkers and construction of prognostic model based on tumor microenvironment.
Bao Q et al.·Eur J Med Res
2025Functional
Epidermal growth factor dampens pro-inflammatory gene expression induced by interferon-gamma in global transcriptome analysis of keratinocytes.
Gibbs DC et al.·BMC Genomics
2025
Polymorphism of HLA-DMA and DMB alleles in patients with systemic lupus erythematosus.
Morel J et al.·J Rheumatol
2003Cohort
HLA-DMA and HLA-DMB genotyping in patients with systemic lupus erythematosus.
Yen JH et al.·J Rheumatol
1999Clinical trial
Methylome and transcriptome analyses reveal HLA-DMB's contribution to periodontitis development.
Zhao B et al.·PLoS One
2025
An in silico approach to the identification of diagnostic and prognostic markers in low-grade gliomas.
Özbek M et al.·PeerJ
2023
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