HLA-C

Chr 6

major 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]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPsoriasis 1
12
Active trials
Pubs (1 yr)
P/LP submissions
P/LP missense
1.02
LOEUF
DN
Mechanism· predicted
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GeneReview available — HLA-C
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.02LOEUF
pLI 0.000
Z-score 1.51
OE 0.63 (0.401.02)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.13Z-score
OE missense 0.97 (0.861.10)
193 obs / 198.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.63 (0.401.02)
00.351.4
Missense OE?0.97 (0.861.10)
00.61.4
Synonymous OE?0.98
01.21.6
LoF obs/exp: 12 / 19.1Missense obs/exp: 193 / 198.3Syn Z: 0.16

ClinVar Variant Classifications

0 submitted variants 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

AutophagyGalectinsHIV Infections

Study 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.

RECRUITING
NCT04160455Centre Hospitalier Régional d'OrléansStarted 2019-11-07
expression of a panel
Diabetic Foot Ulcer (DFU)Venous Leg Ulcer (VLU)

Safety and Preliminary Efficacy of TrophiPatch, an Adipose-Derived Stromal Cell Patch for Chronic Leg Ulcers

RECRUITING
NCT07048054Phase PHASE1, PHASE2Nicolò BrembillaStarted 2025-07
TrophiPatch: allogeneic adipose-derived stromal cell patch
Acute Myeloid LeukemiaMinimal Residual DiseaseNatural Killer Cell

Infusion of Alloreactive nk Cells for Mrd-positive Aml Patients

RECRUITING
NCT06885476Phase NAIRCCS Azienda Ospedaliero-Universitaria di BolognaStarted 2021-01-22
Infusion of alloreactive NK cells
Hodgkin DiseaseNon-Hodgkin LymphomaSevere Chronic Active Epstein Barr Virus

Most Closely Matched 3rd Party Rapidly Generated LMP, BARF1 And EBNA1 Specific CTL, EBV-Positive Lymphoma (MABEL)

ACTIVE NOT RECRUITING
NCT02287311Phase PHASE1Baylor College of MedicineStarted 2015-02
MABEL CTLsCyclophosphamideFludarabine
SepsisSeptic Shock

Myeloid Bias in the Bone Marrow of Septic Patients and Its Correlation With Disease Severity and Prognosis: A Single-Center, Prospective Cohort Study

NOT YET RECRUITING
NCT07667153Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyStarted 2026-07-15
Bone marrow aspirate collection
Type 1 Diabetes Mellitus

Clinical Phase II/III Trial of Ustekinumab to Treat Type 1 Diabetes (UST1D2)

ACTIVE NOT RECRUITING
NCT03941132Phase PHASE2, PHASE3University of British ColumbiaStarted 2021-01-04
UstekinumabPlacebo
Metastatic Uveal MelanomaCutaneous MelanomaColorectal Cancer

Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions

RECRUITING
NCT03947385Phase PHASE1, PHASE2IDEAYA BiosciencesStarted 2019-06-28
IDE196BinimetinibCrizotinib
Breast Cancer Early Stage Breast Cancer (Stage 1-3)Prehabilitation

Multimodal Prehabilitation Program That Combines Physical Exercise, Psychological Intervention and Nutritional Support to Improve the Response to Neoadjuvant Chemoterhapy in Early Breast Cancer Patients

RECRUITING
NCT07107594Phase NAHospital Clinic of BarcelonaStarted 2025-01-14
Multimodal prehabilitation
HIV InfectionsImmune ActivationComorbidities

The University of Zimbabwe College of Health Science (UZ-CHS) BIRTH COHORT Study

ACTIVE NOT RECRUITING
NCT04087239University of ZimbabweStarted 2016-01-26
HIV
Type 1 Diabetes

Characterization of Autoreactive Regulatory and Conventional CD4 T Cells in Recent Onset Type 1 Diabetes and Control Individuals

RECRUITING
NCT06427421Phase NAAssistance Publique - Hôpitaux de ParisStarted 2025-05-06
Frequency of Treg and TeffsPhenotype of Treg and TeffsRNA seq analysis
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
Desmoid FibromatosisRecurrent Desmoid FibromatosisUnresectable Desmoid Fibromatosis

A Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery

ACTIVE NOT RECRUITING
NCT04195399Phase PHASE2Children's Oncology GroupStarted 2020-10-07
Biospecimen CollectionComputed TomographyEchocardiography Test