HLA-A
Chr 6major histocompatibility complex, class I, A
Also known as: HLAA
HLA-A 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 so that they can be recognized by cytotoxic T cells. 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, exons 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. More than 6000 HLA-A alleles have been described. The HLA system plays an important role in the occurrence and outcome of infectious diseases, including those caused by the malaria parasite, the human immunodeficiency virus (HIV), and the severe acute respiratory syndrome coronavirus (SARS-CoV). The structural spike and the nucleocapsid proteins of the novel coronavirus SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), are reported to contain multiple Class I epitopes with predicted HLA restrictions. Individual HLA genetic variation may help explain different immune responses to a virus across a population.[provided by RefSeq, Aug 2020]
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
ClinVar Variant Classifications
23 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 5 | 0 | 5 |
Likely Pathogenic | 1 | 0 | 1 | 0 | 2 |
VUS | 1 | 1 | 6 | 0 | 8 |
Likely Benign | 0 | 1 | 2 | 1 | 4 |
Benign | 0 | 2 | 2 | 0 | 4 |
| Total | 2 | 4 | 16 | 1 | 23 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
HLA-A · 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
{Hypersensitivity syndrome, carbamazepine-induced, susceptibility to}
MIM #608579Molecular basis of disorder known
External Resources
Links to major genomics databases and tools
Variant Interpretation
Population Databases
Gene Resources
Expert Curation
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
EXtremely Early-onset Type 1 Diabetes EXtremely Early-onset Type 1 Diabetes (A Musketeers' Memorandum Study)
RECRUITINGCRISPR-Edited HLA Donor Kidney Transplant to Reduce Rejection Risk
RECRUITINGColangioids to Define the Genetic Factors Involved in Atypical Primary Sclerosing Cholangitis
ACTIVE NOT RECRUITINGMAGE-C2 TCR T Cell Trial to Treat Melanoma and Head and Neck Cancer
RECRUITINGA Vaccine (Neoantigen-Targeted ppDC) for the Treatment of H3 G34-mutant Diffuse Hemispheric Glioma
ACTIVE NOT RECRUITINGStudy of Populations at Risk of Developing Chronic Hepatitis Linked to Chronic Enteric Virus Infection in Patients With Primary Immunodeficiency and Secondary Humoral Deficiency
RECRUITINGMaster Protocol to Assess the Safety and Antitumor Activity of Genetically Engineered T Cells in NY-ESO-1 and/or LAGE-1a Positive Solid Tumors
ACTIVE NOT RECRUITINGImmune Response to Anti-HER2 Therapies in Patients With HER2-Positive Stage I-IV Breast Cancer
RECRUITINGRare Tumor Focused Platform Study of Innovative Therapies and Technologies (PLATFORM2)
NOT YET RECRUITINGNext-gen Flow Cytometry to Find Immune Profiles, Treatment Response, and Toxicity Markers in Skin Cancer Patients Treated With Cemiplimab.
RECRUITINGInnate Immunity, MIcrobiota and Inovative Treatments in Endometriosis
NOT YET RECRUITINGAnalysis of Circulating Tumor mArkers in Blood 4 - ALCINA 4
RECRUITINGExternal Resources
Links to major genomics databases and tools