HLA-A

Chr 6

major 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

{Hypersensitivity syndrome, carbamazepine-induced, susceptibility to}MIM #608579
23
ClinVar variants
7
Pathogenic / LP
0.00
pLI score
12
Active trials
Clinical SummaryHLA-A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 8 VUS of 23 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.75LOEUF
pLI 0.001
Z-score 2.36
OE 0.42 (0.240.75)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.10Z-score
OE missense 1.02 (0.911.14)
214 obs / 210.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.42 (0.240.75)
00.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.02 (0.911.14)
00.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
01.21.6
LoF obs/exp: 8 / 19.1Missense obs/exp: 214 / 210.1Syn Z: 0.62

ClinVar Variant Classifications

23 submitted variants in ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic2
VUS8
Likely Benign4
Benign4
5
Pathogenic
2
Likely Pathogenic
8
VUS
4
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
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
Total2416123

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 #608579

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
HLA molecular typing.
Milford EL·Curr Opin Nephrol Hypertens
1993Review
[Birdshot retinochoroidopathy: Key messages].
Touhami S et al.·J Fr Ophtalmol
2016Review
Vancomycin-Induced Liver Injury, DRESS, and HLA-A∗32:01.
Asif BA et al.·J Allergy Clin Immunol Pract
2024
Polymorphisms of HLA-B: influences on assembly and immunity.
Olson E et al.·Curr Opin Immunol
2020Review
[HLA loss in aplastic anemia].
Zaimoku Y·Rinsho Ketsueki
2025Review
Top 10 resultsSearch PubMed ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Type1 Diabetes Mellitus

EXtremely Early-onset Type 1 Diabetes EXtremely Early-onset Type 1 Diabetes (A Musketeers' Memorandum Study)

RECRUITING
NCT03369821University of ExeterStarted 2017-09-19
Beta Cell Loss and Immune FunctionImmune Function with RNAseq
End-Stage Renal DiseaseEnd Stage Renal Disease on DialysisEnd Stage Renal Disease With Renal Transplant

CRISPR-Edited HLA Donor Kidney Transplant to Reduce Rejection Risk

RECRUITING
NCT07053462Phase PHASE1, PHASE2AMERICAN ORGAN TRANSPLANT AND CANCER RESEARCH INSTITUTE LLCStarted 2025-06-01
Ex Vivo CRISPR-Cas9 Gene Editing of Donor KidneyKidney Transplantation with Standard Care
PSC

Colangioids to Define the Genetic Factors Involved in Atypical Primary Sclerosing Cholangitis

ACTIVE NOT RECRUITING
NCT06865924Phase NAFondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoStarted 2024-12-01
Use of assembloids as in vitro models to test new pharmacological approaches
MelanomaMelanoma, UvealHead and Neck Cancer

MAGE-C2 TCR T Cell Trial to Treat Melanoma and Head and Neck Cancer

RECRUITING
NCT04729543Phase PHASE1, PHASE2Erasmus Medical CenterStarted 2020-10-20
Adoptive therapy with autologous MC2 TCR T cells
Diffuse Hemispheric Glioma, H3 G34-Mutant

A Vaccine (Neoantigen-Targeted ppDC) for the Treatment of H3 G34-mutant Diffuse Hemispheric Glioma

ACTIVE NOT RECRUITING
NCT06342908Phase PHASE1Jonsson Comprehensive Cancer CenterStarted 2024-06-14
Biospecimen CollectionDendritic Cell TherapyLeukapheresis
Humoral Primary Immunodeficiencies (PIDs)Secondary Form of Humoral ImmunodeficienciesCombined Immunodeficiency (CID)

Study of Populations at Risk of Developing Chronic Hepatitis Linked to Chronic Enteric Virus Infection in Patients With Primary Immunodeficiency and Secondary Humoral Deficiency

RECRUITING
NCT06659588Assistance Publique - Hôpitaux de ParisStarted 2024-10-10
Plasma, urine and stool collection
Neoplasms

Master 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 RECRUITING
NCT03967223Phase PHASE2USWM CT, LLCStarted 2019-12-31
Letetresgene autoleucel (lete-cel, GSK3377794)FludarabineCyclophosphamide
Breast AdenocarcinomaHER2-Positive Breast CarcinomaAnatomic Stage I Breast Cancer AJCC v8

Immune Response to Anti-HER2 Therapies in Patients With HER2-Positive Stage I-IV Breast Cancer

RECRUITING
NCT04517838Mayo ClinicStarted 2020-07-31
Biospecimen Collection
Rare Malignant NeoplasmAdvanced Solid TumorsMetastatic Solid Tumors

Rare Tumor Focused Platform Study of Innovative Therapies and Technologies (PLATFORM2)

NOT YET RECRUITING
NCT07307053Phase PHASE1, PHASE2Cancer Institute and Hospital, Chinese Academy of Medical SciencesStarted 2026-01-01
BL-B01D1VSV injectionCVL006
Cutaneous Squamous Cell Carcinoma (CSCC)

Next-gen Flow Cytometry to Find Immune Profiles, Treatment Response, and Toxicity Markers in Skin Cancer Patients Treated With Cemiplimab.

RECRUITING
NCT07064330Instituto de Investigación Biomédica de SalamancaStarted 2025-07-17
Cemiplimab
EndometriosisImmunityMicrobiota

Innate Immunity, MIcrobiota and Inovative Treatments in Endometriosis

NOT YET RECRUITING
NCT07078435Phase NAUniversity Hospital, GrenobleStarted 2025-09-09
surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelinesBlood testStool samples
Cancer

Analysis of Circulating Tumor mArkers in Blood 4 - ALCINA 4

RECRUITING
NCT05088395Phase NAInstitut CurieStarted 2022-05-19
Blood sampleBiopsy