HLA-B Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the HLA-B gene, its protein product, associated diseases, and clinical relevance.
Gene Information Card
| Symbol | HLA-B |
|---|---|
| Full Name | Major Histocompatibility Complex, Class I, B |
| Gene Type | Protein coding |
| Chromosomal Location | 6p21.33 |
| NCBI Gene ID | 3106 ncbi.nlm.nih.gov/gene/3106 |
| Ensembl ID | ENSG00000234745 |
| UniProt ID | P01889 |
| OMIM ID | 142830 |
| HGNC ID | 4932 |
| Aliases | AS, SPDA1, HLA-B*27, HLA-B27 |
Description
The HLA-B gene encodes the human leukocyte antigen class I (MHC class I) heavy chain, a highly polymorphic cell-surface glycoprotein essential for the adaptive immune system. Its primary function is to present endogenous (intracellular) peptides, including viral and tumor antigens, to CD8+ T lymphocytes (cytotoxic T cells). This presentation is crucial for immune surveillance and the elimination of infected or malignant cells. The extreme polymorphism of HLA-B allows the immune system to present a diverse array of peptides to T cells. HLA-B is also a major histocompatibility (transplantation) antigen, making it a critical factor in organ and hematopoietic stem cell transplantation matching. Certain HLA-B alleles are strongly associated with specific diseases, including autoimmune conditions like ankylosing spondylitis (HLA-B27) and severe drug hypersensitivity reactions like Stevens-Johnson syndrome (HLA-B*15:02).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ankylosing Spondylitis | The HLA-B27 allele is the strongest known genetic risk factor. The mechanism is not fully understood but is thought to involve the presentation of arthritogenic peptides, the formation of misfolded HLA-B27 heavy chain homodimers that trigger pro-inflammatory responses, or the activation of autoreactive T cells. | Strong genetic association (GWAS, case-control studies). |
| Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN) | The HLA-B*15:02 allele is strongly associated with SJS/TEN induced by carbamazepine and other aromatic antiepileptic drugs. The mechanism is believed to be a direct, non-covalent interaction between the drug and the HLA-B*15:02 molecule, leading to an altered peptide repertoire and an inappropriate CD8+ T-cell response. | Strong genetic association in specific populations (e.g., Han Chinese, Southeast Asian). |
| HIV/AIDS | Certain HLA-B alleles, such as HLA-B*57 and HLA-B*27, are associated with slower progression to AIDS and better control of viral load. This is likely due to the effective presentation of highly conserved HIV epitopes, leading to a robust and broadly reactive CD8+ T-cell response. | Strong genetic association (cohort studies). |
| Behçet's Disease | HLA-B*51 is the most significant genetic risk factor for Behçet's disease, a systemic inflammatory disorder. The mechanism is not fully understood but is thought to involve altered antigen presentation leading to an exaggerated inflammatory response. | Strong genetic association (case-control studies). |
| Graft-versus-Host Disease (GVHD) | HLA-B is a major histocompatibility antigen. Mismatches in HLA-B between donor and recipient in allogeneic hematopoietic stem cell transplantation are a primary cause of acute GVHD, where donor T cells recognize recipient tissues as foreign. | Clinical evidence (transplantation outcome studies). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Whole Blood | N/A | High |
| Spleen | N/A | High |
| Lymph Node | N/A | High |
| Bone Marrow | N/A | High |
| Lung | N/A | Medium |
| Liver | N/A | Medium |
| Kidney | N/A | Medium |
| Skin | N/A | Medium |
| Brain | N/A | Low |
| Muscle | N/A | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| B-lymphocyte (GM12878) | N/A | High expression |
| T-lymphocyte (Jurkat) | N/A | High expression |
| Monocyte (THP-1) | N/A | High expression |
| NK cell (NK-92) | N/A | High expression |
| HeLa (cervical cancer) | N/A | Medium expression |
| A549 (lung cancer) | N/A | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| HLA-B*27:05 | Allelic Variant | ~8% in Caucasian populations | Strongly associated with Ankylosing Spondylitis. The mechanism is not fully defined but is thought to involve the presentation of specific self-peptides or the formation of misfolded heavy chains. |
| HLA-B*57:01 | Allelic Variant | ~5-10% in Caucasian populations | Associated with abacavir hypersensitivity and with better control of HIV infection. The abacavir interaction is a direct, non-covalent binding to the antigen-binding cleft, altering the peptide repertoire. |
| HLA-B*15:02 | Allelic Variant | ~10-15% in Han Chinese populations | Strongly associated with carbamazepine-induced Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN). The mechanism involves a direct drug-HLA interaction. |
| HLA-B*51:01 | Allelic Variant | ~10-20% in Middle Eastern and Asian populations | Strongly associated with Behçet's disease. The mechanism is not fully understood but is thought to involve altered antigen presentation and an enhanced inflammatory response. |
Mutation functional classification
Loss of Function (LOF)
Complete loss of function is rare and would likely result in severe immunodeficiency due to the absence of a functional MHC class I antigen presentation pathway. However, no common loss-of-function variants are known, as this would be highly deleterious.
Gain of Function (GOF)
Not applicable in the traditional sense. The 'function' of HLA-B is to present peptides. Allelic variants are not 'gain-of-function' but rather 'altered-function' or 'neofunction', where the new allele presents a different repertoire of peptides, which can be either beneficial (e.g., HIV control) or detrimental (e.g., autoimmunity or drug hypersensitivity).
Dominant Negative (DN)
Not applicable. HLA-B is co-dominantly expressed. Both alleles are expressed on the cell surface. A dominant-negative effect would require one allele to interfere with the function of the other, which is not a known mechanism for HLA-B.
View complete mutation data：
Gene Ontology (GO)
| • MHC class I protein complex | • peptide antigen binding |
| • immune response | • antigen processing and presentation of exogenous peptide antigen via MHC class I |
| • TAP-dependent peptide antigen presentation | • positive regulation of T cell mediated cytotoxicity |
| • cell surface receptor signaling pathway | • response to virus |
Pathways
• Antigen processing and presentation (KEGG hsa04612)
• Allograft rejection (KEGG hsa05330)
• Graft-versus-host disease (KEGG hsa05332)
• Type I diabetes mellitus (KEGG hsa04940)
• Viral myocarditis (KEGG hsa05416)
• Autoimmune thyroid disease (KEGG hsa05320)
Protein Summary
The HLA-B protein is a single-pass type I membrane glycoprotein that forms a heterodimer with beta-2-microglobulin (B2M). It consists of three extracellular domains (alpha-1, alpha-2, and alpha-3), a transmembrane domain, and a short cytoplasmic tail. The alpha-1 and alpha-2 domains form the peptide-binding groove, a highly polymorphic region that determines the repertoire of peptides that can be presented. The alpha-3 domain is conserved and contains the binding site for the CD8 co-receptor on T cells. The protein is synthesized in the endoplasmic reticulum (ER), where it assembles with B2M and a peptide cargo. The peptide-loaded complex is then transported to the cell surface for presentation to CD8+ T cells. The extreme polymorphism of the peptide-binding groove is the basis for the diverse immune responses and disease associations seen with different HLA-B alleles.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HLA-B Knockout HEK293 Cell Line | EDJ-KQ13753 | Human | 3106 | Details Get a Quote |
| HLA-B Knockout A-549 Cell Line | EDJ-KQ43525 | Human | 3106 | Details Get a Quote |
| HLA-B Knockout HCT 116 Cell Line | EDJ-KQ43526 | Human | 3106 | Details Get a Quote |
| HLA-B Knockout HeLa Cell Line | EDJ-KQ43527 | Human | 3106 | Details Get a Quote |
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