HLA-DOB

Chr 6

major histocompatibility complex, class II, DO beta

Also known as: DOB, HLA_DOB

NCBI Gene: 3112ENSG00000241106UniProt: P13765

HLA-DOB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DOA) and a beta chain (DOB), both anchored in the membrane. It is located in intracellular vesicles. DO suppresses peptide loading of MHC class II molecules by inhibiting HLA-DM. 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-DOB
⚡
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

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.
1.35LOEUF
pLI 0.000
Z-score 0.66
OE 0.80 (0.49–1.35)
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.
0.18Z-score
OE missense 0.96 (0.83–1.10)
136 obs / 141.9 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.0.80 (0.49–1.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.83–1.10)
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.1.06
0≤1.21.6
LoF obs/exp: 10 / 12.5Missense obs/exp: 136 / 141.9Syn Z: -0.36

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-DOB · 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
Identification and validation of CKAP2 as a novel biomarker in the development and progression of rheumatoid arthritis.
Zheng Q et al.·Front Immunol
2025
MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil.
Castelli EC et al.·Front Immunol
2022
Bioinformatics analysis of the clinical significance of HLA class II in breast cancer.
Wu G et al.·Medicine (Baltimore)
2022
Pilot Exploration of RGMa-BMP4 Signaling in Neutrophil Activation in NMOSD: Integrating Clinical and Molecular Insights.
Zhang W et al.·Mol Neurobiol
2025
Identifying dynamic pathway interactions based on clinical information.
Kim S·Comput Biol Chem
2017
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
Clinical and genetic characteristics of ankylosing spondylitis patients with peripheral arthritis at disease onset.
Polo Y La Borda J et al.·Clin Exp Rheumatol
2019Cohort
Inositol 1,4,5-trisphosphate receptor gene variants are related to the risk of breast cancer in a Chinese population.
Chen J et al.·J Gene Med
2023
Genotyping of immune-related loci associated with delayed HBeAg seroconversion in immune-active chronic hepatitis B patients.
Liu WC et al.·Antiviral Res
2020Cohort
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