HLA-B
protein-codingmajor histocompatibility complex, class I, B, the group of C1-set domain containing|Histocompatibility complex|MicroRNA protein coding host genes
Gene summary
HLA-B belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exon 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Hundreds of HLA-B alleles have been described. [provided by RefSeq, Jul 2008]
- AS
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: General
Intervention: Pharmacogenomic
Rationale: Susceptibility to adverse reactions (including Stevens-Johnson syndrome), may have pharmacogenomic importance related to a number of medications, including abacavir, allopurinol, carbamazepine, flucocloxacillin
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HLA-B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005514.8. 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 | 5 | 22 | 1 | 28 | ||
| missense | 13 | 4 | 1 | 18 | ||
| nonsense | 1 | 2 | 3 | |||
| start loss | 0 | |||||
| frameshift | 3 | 1 | 4 | |||
| splice donor/acceptor (+/-2bp) | 20 | 20 | ||||
| Total | 1 | 0 | 40 | 29 | 3 | 73 |
Highest pathogenic variant AF is 0.000004569
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005505.2 | 7 | MANE Select | |
| Ensembl | ENSP00000399168.2 | 7 | MANE Select | |
| Ensembl | ENSP00000491275.2 | 6 | Standard | |
| Ensembl | ENSP00000512716.1 | 4 | 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)
- Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
- Allograft rejection - Homo sapiens (human)
Biological Process
- positive regulation of T cell mediated cytotoxicity
- antigen processing and presentation of peptide antigen via MHC class I
- antigen processing and presentation of endogenous peptide antigen via MHC class Ib
- antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
- antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent
Molecular Function
- signaling receptor binding
- protein binding
- peptide antigen binding
Cellular Component
- Golgi membrane
- extracellular space
- endoplasmic reticulum
- Golgi apparatus
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000412585
- Coding exons
- 7
- Length
- 3317
- Individuals with no LoFs
- 27804
- Homozygous LoFs
- 62749
- Heterozygous LoFs
- 35194
- Defined
- 125747
- p
- 0.530
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0112 | 196 | 196 | 1.00 | 0.00000977 | 2123 |
| Missense (PolyPhen) | 110 | 130.87 | 0.84052 | 1447 | ||
| Synonymous | 0.131 | 77 | 78.5 | 0.981 | 0.00000423 | 660 |
| Loss of Function | 1.85 | 10 | 18.6 | 0.538 | 8.04e-7 | 194 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 1.1 | 0.46 | notable |
| Latino/Admixed American | 1.1 | 0.64 | notable |
| Ashkenazi Jewish | 1.3 | 0.65 | notable |
| East Asian | 0.86 | 0.52 | notable |
| Finnish | 1.0 | 0.48 | notable |
| European (Non-Finnish) | 1.2 | 0.50 | notable |
| South Asian | 1.3 | 0.60 | notable |
| Other | 1.2 | 0.51 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the presentation of foreign antigens to the immune system.;
Intolerance Scores
- LoFtool
- 0.996
- RVIS EVS
- 8.95
- RVIS percentile EVS
- 99.96
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.447
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |