HLA-DOB
protein-codingmajor histocompatibility complex, class II, DO beta, the group of C1-set domain containing|Histocompatibility complex
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HLA-DOB variants in ClinVar
No annotated ClinVar phenotypes.
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002120.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 0 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 1 | 0 | 0 | 1 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002111.1 | 6 | MANE Select | |
| Ensembl | ENSP00000390020.2 | 6 | MANE Select | |
| Ensembl | ENSP00000394860.1 | 3 | Standard | |
| Ensembl | ENSP00000436618.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Antigen processing and presentation - Homo sapiens (human)
- Cell adhesion molecules (CAMs) - Homo sapiens (human)
- Type I diabetes mellitus - Homo sapiens (human)
- Allograft rejection - Homo sapiens (human)
- Graft-versus-host disease - Homo sapiens (human)
Biological Process
- negative regulation of antigen processing and presentation of peptide antigen via MHC class II
- immune response
- antigen processing and presentation of exogenous peptide antigen via MHC class II
Molecular Function
- MHC class II protein complex binding
- MHC class II receptor activity
Cellular Component
- lysosome
- lysosomal membrane
- endosome membrane
- integral component of membrane
- MHC class II protein complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000438763
- Coding exons
- 6
- Length
- 4286
- Individuals with no LoFs
- 125602
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 146
- Defined
- 125748
- p
- 0.000581
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.177 | 136 | 142 | 0.958 | 0.00000704 | 1764 |
| Missense (PolyPhen) | 45 | 52.83 | 0.85179 | 691 | ||
| Synonymous | -0.356 | 61 | 57.6 | 1.06 | 0.00000308 | 545 |
| Loss of Function | 0.659 | 10 | 12.5 | 0.799 | 6.22e-7 | 137 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00052 | 0.00049 | rare |
| Latino/Admixed American | 0.00020 | 0.00020 | rare |
| Ashkenazi Jewish | 0.00040 | 0.00040 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0011 | 0.0011 | notable |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00066 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: 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.;
Recessive Scores
- pRec
- 0.123
Intolerance Scores
- LoFtool
- 0.729
- RVIS EVS
- 0.73
- RVIS percentile EVS
- 86.08
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.724
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |