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GeneE
50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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HLA-A
major histocompatibility complex, class I, A
Chromosome 6 · 6p22.1
NCBI Gene: 3105Ensembl: ENSG00000206503.16HGNC: HGNC:4931UniProt: B1PKY1
1,676PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Highly Studied
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
T cell mediated cytotoxicity directed against tumor cell targetRNA bindingsignaling receptor bindingprotein bindingdiffuse large B-cell lymphomaHIV infectionCOVID-19squamous cell lung carcinoma
✦AI Summary

HLA-A is a major histocompatibility complex class I molecule essential for adaptive and innate immunity. It functions primarily as a peptide-presenting protein that displays antigenic epitopes on cell surfaces for recognition by CD8+ T cells 1. HLA-A achieves this through assembly with beta-2-microglobulin and processed peptide antigens, forming stable complexes that bind CD8 receptors on T lymphocytes 2. The mechanism involves loading peptides derived from viral, bacterial, or self-antigens into the peptide-binding groove, enabling both TAP-dependent and TAP-independent antigen processing pathways 3. Specific HLA-A alleles demonstrate clinical relevance in infectious disease control. For example, HLA-A*1101 restricts CD8+ T cell responses against human cytomegalovirus, enabling tetramer-based detection of virus-specific immunity 1. HLA-A*0201-based recombinant constructs elicit CD8+ T cell proliferation and have been evaluated as potential HIV vaccine candidates 2. The considerable allelic diversity of HLA-A, including newly identified variants 456, underlies population-level variation in immunological responses and disease susceptibility. Molecular typing methods are essential for accurate HLA-A characterization in clinical and research contexts 3.

Sources cited
1
Molecular genotyping and protein biochemistry methods for HLA-A typing; discrepancies between serologic and DNA typing; importance for functional experiments
PMID: 9924694
2
HLA-A*1101 tetramer preparation with CMV peptide; binding to CD8+ T cells; study of virus-specific CD8+ T cell responses
PMID: 17484809
3
HLA-A*0201 recombinant construct with beta-2-microglobulin; elicits CD8+ and CD4+ T cell responses; potential HIV vaccine application
PMID: 20542039
4
Novel HLA-A allele HLA-A*01:353 identification
PMID: 33034166
5
HLA-A*23:68 allele with amino acid substitution at position 149
PMID: 26814410
6
Novel HLA-A*01:420N null allele with premature stop codon
PMID: 36268577
Disease Associationsⓘ20
diffuse large B-cell lymphomaOpen Targets
0.54Moderate
HIV infectionOpen Targets
0.53Moderate
COVID-19Open Targets
0.48Moderate
squamous cell lung carcinomaOpen Targets
0.42Moderate
head and neck squamous cell carcinomaOpen Targets
0.41Moderate
cervical squamous cell carcinomaOpen Targets
0.38Weak
acute myeloid leukemiaOpen Targets
0.37Weak
melanocytic neoplasmOpen Targets
0.37Weak
nasopharyngeal neoplasmOpen Targets
0.37Weak
spitz nevusOpen Targets
0.37Weak
urinary bladder cancerOpen Targets
0.34Weak
Burkitts lymphomaOpen Targets
0.29Weak
melanomaOpen Targets
0.23Weak
colon adenocarcinomaOpen Targets
0.22Weak
adult T-cell leukemia/lymphomaOpen Targets
0.20Weak
gliomaOpen Targets
0.20Weak
non-small cell lung carcinomaOpen Targets
0.20Weak
Hodgkins lymphomaOpen Targets
0.20Weak
hepatocellular carcinomaOpen Targets
0.19Weak
small cell lung carcinomaOpen Targets
0.19Weak
Pathogenic Variants1
NM_002116.8(HLA-A):c.704_722del (p.Ala235fs)Likely pathogenic
Susceptibility to severe COVID-19
★☆☆☆2024→ Residue 235
View on ClinVar ↗
Related Genes
LILRB1Protein interaction100%AP1M1Protein interaction100%AP1S3Protein interaction100%KIR2DS5Protein interaction100%LILRB4Protein interaction100%LILRA6Protein interaction100%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
78%
Heart
43%
Liver
31%
Ovary
26%
Brain
19%
Gene Interaction Network
Click a node to explore
HLA-ALILRB1AP1M1AP1S3KIR2DS5LILRB4LILRA6
PROTEIN STRUCTURE
Preparing viewer…
PDB3MRE · 1.10 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.98LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF2.60 [1.15–1.98]
RankingsWhere HLA-A stands among ~20K protein-coding genes
  • #70of 20,598
    Most Researched1,676 · top 1%
  • #4,597of 5,498
    Most Pathogenic Variants1
  • #17,809of 17,882
    Most Constrained (LOEUF)1.98
Genes detectedHLA-A
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
Obituary.
PMID: 27283134
HLA · 2016
1.00
2
Human endogenous retrovirus (HERVK9) structural polymorphism with haplotypic HLA-A allelic associations.
PMID: 18757922
Genetics · 2008
1.00
3
Determination of HLA-A, -C, -B, -DRB1 allele and haplotype frequency in Japanese population based on family study.
PMID: 25789826
Tissue Antigens · 2015
0.98
4
Identification of four novel HLA-A alleles.
PMID: 32277603
HLA · 2020
0.96
5
Plasticity of human CD8αα binding to peptide-HLA-A*2402.
PMID: 21645925
Mol Immunol · 2011
0.94