{"entity":{"id":"hla-c","kind":"target","name":"HLA-C","aka":["major histocompatibility complex, class I, C","HLA class I histocompatibility antigen, C alpha chain","HLA-JY3","D6S204","PSORS1"],"tldr":"HLA-C (HLA class I histocompatibility antigen, C alpha chain) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Colorectal cancer and Diffuse large B-cell lymphoma.","summary":"Antigen-presenting major histocompatibility complex class I (MHCI) molecule with an important role in reproduction and antiviral immunity. In complex with B2M/beta 2 microglobulin displays a restricted repertoire of self and viral peptides and acts as a dominant ligand for inhibitory and activating killer immunoglobulin receptors (KIRs) expressed on NK cells. In an allogeneic setting, such as during pregnancy, mediates interaction of extravillous trophoblasts with KIR on uterine NK cells and regulate trophoblast invasion necessary for placentation and overall fetal growth.\n\nCIViC holds 2 clinical evidence items and 0 assertions across 2 variants, naming Therapeutic Tumour Infiltrating Lymphocytes. IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Diffuse Large B-Cell Lymphoma, NOS.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:4933","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4933"},{"label":"UniProt P10321","url":"https://www.uniprot.org/uniprotkb/P10321/entry"},{"label":"NCBI Gene 3107","url":"https://www.ncbi.nlm.nih.gov/gene/3107"},{"label":"Ensembl ENSG00000204525","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000204525"}],"tags":["cancer-genes-wave"],"related":["civic","intogen"],"cancers":["colorectal","dlbcl"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 1 therapies; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; CIViC holds 2 clinical evidence items on its variants. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"HLA-C","role":["drug-target","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:4933","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4933","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P10321","url":"https://www.uniprot.org/uniprotkb/P10321/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene HLA-C","url":"https://civicdb.org/features/2608","note":"2 evidence items, 0 assertions, 2 variants; diseases: Colorectal Cancer, Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"IntOGen HLA-C","url":"https://www.intogen.org/search?gene=HLA-C","note":"driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"few-types","specificityNote":"Tumour-specific alteration: the catalogues call it a tumour suppressor (IntOGen finds it knocked out more often than chance); what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA HLA-C: RNA tissue enhanced (lymphoid tissue 1,378 nTPM); no normal tissue stained high. Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Colorectal cancer, Lymphoma); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P10321","url":"https://www.uniprot.org/uniprotkb/P10321/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene HLA-C","url":"https://civicdb.org/features/2608","note":"2 evidence items, 0 assertions, 2 variants; diseases: Colorectal Cancer, Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"IntOGen HLA-C","url":"https://www.intogen.org/search?gene=HLA-C","note":"driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas HLA-C tissue","url":"https://www.proteinatlas.org/ENSG00000204525-HLA-C/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000204525 associations","url":"https://platform.opentargets.org/target/ENSG00000204525/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:4933","ensembl":"ENSG00000204525","uniprot":"P10321","entrez":"3107","firstDescribed":1989,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Cianetti et al, Immunogenetics, 1989, \"Three new class I HLA alleles: structure of mRNAs and alternative mechanisms of processing\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2914713/","biology":"Antigen-presenting major histocompatibility complex class I (MHCI) molecule with an important role in reproduction and antiviral immunity. In complex with B2M/beta 2 microglobulin displays a restricted repertoire of self and viral peptides and acts as a dominant ligand for inhibitory and activating killer immunoglobulin receptors (KIRs) expressed on NK cells. In an allogeneic setting, such as during pregnancy, mediates interaction of extravillous trophoblasts with KIR on uterine NK cells and regulate trophoblast invasion necessary for placentation and overall fetal growth. During viral infection, may present viral peptides with low affinity for KIRs, impeding KIR-mediated inhibition through peptide antagonism and favoring lysis of infected cells. Presents a restricted repertoire of viral peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-C-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected cells, particularly in chronic viral infection settings such as HIV-1 or CMV infection. Both the peptide and the MHC molecule are recognised by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells. Location: Cell membrane; Endoplasmic reticulum membrane (UniProt). Locus 6p21.33 (HGNC).","whereFound":["Colorectal cancer: CIViC evidence names this disease","Diffuse large B-cell lymphoma: CIViC evidence names this disease; IntOGen driver in 1 cohort (DLBCLNOS)"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/hla-c/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"}]}}