HLA-DMB

Chr 6

major histocompatibility complex, class II, DM beta

Also known as: D6S221E, RING7

NCBI Gene: 3109ENSG00000242574UniProt: P28068

HLA-DMB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DMA) and a beta (DMB) chain, 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 (class II-associated invariant chain peptide) molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. [provided by RefSeq, Jul 2008]

7
ClinVar variants
5
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HLA-DMB
⚡
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 7 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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 1.63
OE 0.49 (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.
1.59Z-score
OE missense 0.63 (0.53–0.75)
89 obs / 142.3 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.0.49 (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.0.63 (0.53–0.75)
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.0.97
0≤1.21.6
LoF obs/exp: 6 / 12.1Missense obs/exp: 89 / 142.3Syn Z: 0.18

ClinVar Variant Classifications

7 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS2
4
Pathogenic
1
Likely Pathogenic
2
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————4
Likely Pathogenic
————1
VUS
————2
Likely Benign
————0
Benign
————0
Total—7

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HLA-DMB · 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
Methylome and transcriptome analyses reveal HLA-DMB's contribution to periodontitis development.
Zhao B et al.·PLoS One
2025
HLA-DMB gene and HLA-DRA promoter region polymorphisms in Australian multiple sclerosis patients.
Bennetts BH et al.·Hum Immunol
1999Cohort
Identification of the molecular subtype and prognostic characteristics of lung adenocarcinoma based on CD8(+) T cell-related gene signature.
Tang K et al.·Cancer Biomark
2024
Germline genetic biomarkers to stratify patients for personalized radiation treatment.
Deichaite I et al.·J Transl Med
2022Cohort
HLA-DMA and HLA-DMB genotyping in patients with systemic lupus erythematosus.
Yen JH et al.·J Rheumatol
1999Clinical trial
What causes relapses of autoimmune diseases? The etiological role of autoreactive T cells.
Wildner G et al.·Autoimmun Rev
2013Review
Construction of a novel prognostic model in skin cutaneous melanoma based on chemokines-related gene signature.
Ding X et al.·Sci Rep
2023Functional
SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi's sarcoma.
Aissani B et al.·Genes Immun
2014
CD74, a novel predictor for bronchopulmonary dysplasia in preterm infants.
Gao J et al.·Medicine (Baltimore)
2020
Immunopathology of childhood celiac disease-Key role of intestinal epithelial cells.
Pietz G et al.·PLoS One
2017
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