HLA-C
Chr 6Multimajor histocompatibility complex, class I, C
Also known as: D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1
HLA-C 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 endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domain, 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. About 6000 HLA-C 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
Highly tolerant — LoF variants common in population
Mild missense constraint
ClinVar Variant Classifications
20 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 | 4 | 0 | 4 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 0 | 4 | 0 | 4 |
Likely Benign | 0 | 2 | 1 | 5 | 8 |
Benign | 0 | 1 | 0 | 0 | 1 |
| Total | 0 | 3 | 12 | 5 | 20 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
HLA-C · 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
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)
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
RECRUITINGInnate Immunity, MIcrobiota and Inovative Treatments in Endometriosis
NOT YET RECRUITINGStudy of TBI-1301 (NY-ESO-1 Specific TCR Gene Transduced Autologous T Lymphocytes) in Patients With Solid Tumors
ACTIVE NOT RECRUITINGStudy of Autophagy and the Effects of GALIG Gene Products in HIV-1 Infected Patients Who Are Under Antiretroviral Therapy Since Primary-infection, Chronic Phase, or Never Treated.
RECRUITINGAdministering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12D Variant of Mutated RAS in HLA-A*11:01 Patients
RECRUITINGAllogenic CD19-targeting CAR-γδT Cell Therapy in R/R NHL
RECRUITINGSafety and Preliminary Efficacy of TrophiPatch, an Adipose-Derived Stromal Cell Patch for Chronic Leg Ulcers
RECRUITINGA Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery
ACTIVE NOT RECRUITINGInfusion of Alloreactive nk Cells for Mrd-positive Aml Patients
RECRUITINGAllogeneic TRAC Locus-inserted CD19-targeting STAR T Cell Therapy in r/r B-NHL
RECRUITINGExternal Resources
Links to major genomics databases and tools