HLA-A Gene: Structure, Function, and Clinical Significance
A comprehensive guide to the HLA-A gene, its role in immune presentation, associated diseases, and clinical relevance.
Gene Information Card
| Symbol | HLA-A |
|---|---|
| Full Name | Major Histocompatibility Complex, Class I, A |
| Gene Type | Protein coding |
| Chromosomal Location | 6p21.33 |
| NCBI Gene ID | 3105 ncbi.nlm.nih.gov/gene/3105 |
| Ensembl ID | ENSG00000206503 |
| UniProt ID | P04439 |
| OMIM ID | 142800 |
| HGNC ID | 4931 |
| Aliases | HLAA, HLA-A*11, HLA-A*24, HLA-A*02, MHC class I antigen A*2 |
Description
The HLA-A gene encodes a human leukocyte antigen (HLA) class I heavy chain, a critical component of the adaptive immune system. This protein is expressed on the surface of nearly all nucleated cells and is responsible for presenting endogenous peptides, including viral and tumor antigens, to CD8+ T cells. The HLA-A protein is highly polymorphic, with thousands of known alleles, allowing for a diverse repertoire of antigen presentation across the human population. This polymorphism is the primary cause of transplant rejection and is strongly associated with susceptibility or resistance to numerous autoimmune, infectious, and malignant diseases. The HLA-A gene is located within the major histocompatibility complex (MHC) region on chromosome 6, a genomic area renowned for its high gene density and extensive linkage disequilibrium.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ankylosing Spondylitis | The HLA-A*24:02 allele is associated with increased risk. The mechanism is not fully understood but may involve the presentation of specific self-peptides that trigger an aberrant immune response. | Association studies (PMID: 27992413) |
| Behçet's Disease | HLA-A*26 is a well-established risk allele. The mechanism is thought to involve the presentation of a specific peptide from the HLA-B*51 molecule itself, leading to a cross-reactive T-cell response. | Association studies (PMID: 24934645) |
| HIV/AIDS | Certain HLA-A alleles, such as HLA-A*11 and HLA-A*24, are associated with differential control of HIV-1 viral load. The mechanism involves the efficiency of presenting conserved HIV epitopes to cytotoxic T lymphocytes. | Genome-wide association studies (PMID: 20877624) |
| Cutaneous T-cell Lymphoma (CTCL) | HLA-A*02 is frequently expressed in CTCL tumor cells. The mechanism is not fully defined, but it may involve the presentation of tumor-specific antigens that are not effectively recognized by the immune system, leading to immune evasion. | Expression and association studies (PMID: 23221096) |
| Drug Hypersensitivity (e.g., Abacavir) | HLA-A*31:01 is associated with carbamazepine-induced hypersensitivity. The mechanism involves the drug binding non-covalently to the HLA-A*31:01 molecule, altering the presented peptide repertoire and triggering a T-cell-mediated immune response. | Pharmacogenomic studies (PMID: 21428769) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Whole Blood | ~20 | Medium |
| Lymph Node | ~15 | Medium |
| Spleen | ~12 | Medium |
| Bone Marrow | ~8 | Low |
| Lung | ~5 | Low |
| Liver | ~2 | Low |
| Brain | ~1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (Chronic Myelogenous Leukemia) | ~5 | Low expression; often used as a negative control for HLA class I in flow cytometry. |
| A-431 (Epidermoid Carcinoma) | ~30 | High expression; commonly used as a positive control. |
| HeLa (Cervical Adenocarcinoma) | ~25 | High expression; a standard cell line for studying MHC class I. |
| MCF7 (Breast Adenocarcinoma) | ~15 | Moderate expression; expression can be modulated by interferons. |
| HepG2 (Hepatocellular Carcinoma) | ~10 | Moderate expression; expression is lower than in immune cells. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| HLA-A*02:01 | Common Allele | ~10-15% globally | This is the most common allele in many populations. It is associated with a lower risk of certain cancers but a higher risk of autoimmune diseases like type 1 diabetes. |
| HLA-A*24:02 | Common Allele | ~10-20% in Asian populations | Associated with an increased risk of Ankylosing Spondylitis and a poorer prognosis in some cancers. |
| HLA-A*11:01 | Common Allele | ~10-20% in East Asian populations | Associated with better control of HIV-1 and a reduced risk of certain viral infections. |
| HLA-A*26:01 | Risk Allele | ~5-10% in some populations | Strongly associated with Behçet's disease. |
| HLA-A*31:01 | Risk Allele | ~2-5% in European and Asian populations | Associated with carbamazepine-induced severe cutaneous adverse drug reactions. |
Mutation functional classification
Loss of Function (LOF)
Complete loss-of-function mutations in HLA-A are rare and often lethal in early development due to severe immunodeficiency. However, somatic loss of heterozygosity (LOH) at the HLA locus is frequently observed in tumors, allowing cancer cells to evade T-cell-mediated killing.
Gain of Function (GOF)
Gain-of-function is not a typical classification for HLA-A. The primary functional variation arises from allelic differences that alter the peptide-binding groove, leading to a 'gain' in the ability to present specific novel peptides. This is a normal, non-pathogenic variation.
Dominant Negative (DN)
Dominant-negative effects are not a classic mechanism for HLA-A. However, certain viral proteins, like HIV-1 Nef, can downregulate HLA-A expression, acting as a functional dominant-negative by reducing the cell surface density of the molecule and impairing antigen presentation.
View complete mutation data：
Gene Ontology (GO)
| • MHC class I protein complex binding | • peptide antigen binding |
| • immune response | • antigen processing and presentation of exogenous peptide antigen via MHC class I |
| • antigen processing and presentation of endogenous peptide antigen via MHC class I | • T cell mediated cytotoxicity |
| • positive regulation of T cell mediated cytotoxicity | • cell surface receptor signaling pathway |
| • adaptive immune response | • response to interferon-gamma |
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)
• Phagosome (KEGG hsa04145)
Protein Summary
The HLA-A protein is a single-pass type I membrane glycoprotein composed of three extracellular domains (α1, α2, and α3), a transmembrane domain, and a short cytoplasmic tail. The α1 and α2 domains form the peptide-binding groove, which accommodates peptides of 8-10 amino acids. The α3 domain is highly conserved and serves as the binding site for the CD8 co-receptor on cytotoxic T lymphocytes. The protein is non-covalently associated with β-2-microglobulin, which is essential for stable cell surface expression. The mature protein is heavily glycosylated and is expressed on the surface of all nucleated cells. Its primary function is to display the intracellular protein content to CD8+ T cells, enabling immune surveillance against viral infections and tumors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HLA-A Knockout HEK293 Cell Line | EDJ-KQ13752 | Human | 3105 | Details Get a Quote |
| HLA-A Knockout HeLa Cell Line | EDJ-KQ42265 | Human | 3105 | Details Get a Quote |
| HLA-A Knockout A-549 Cell Line | EDJ-KQ43522 | Human | 3105 | Details Get a Quote |
| HLA-A Knockout HCT 116 Cell Line | EDJ-KQ43523 | Human | 3105 | Details Get a Quote |
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