{"entity":{"id":"ciita","kind":"target","name":"CIITA","aka":["class II major histocompatibility complex transactivator","MHC class II transactivator","C2TA","MHC2TA"],"tldr":"CIITA (MHC class II transactivator) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Head and neck squamous cell carcinoma, Skin cancer, Colorectal cancer and 4 more.","summary":"Essential for transcriptional activity of the HLA class II promoter; activation is via the proximal promoter. Does not bind DNA. May act in a coactivator-like fashion through protein-protein interactions by contacting factors binding to the proximal MHC class II promoter, to elements of the transcription machinery, or both PubMed:8402893, PubMed:7749984,.\n\nCIViC holds 1 clinical evidence item and 0 assertions across 1 variant. Open Targets scores its association with cancer at 0.64 (direct and indirect evidence; datatypes literature 0.91, genetic association 0.00, somatic mutation 0.83). IntOGen calls it a driver in 3 cohorts (2 activating, 1 loss-of-function), covering Diffuse Large B-Cell Lymphoma, NOS, Head and Neck Squamous Cell Carcinoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:7067","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7067"},{"label":"UniProt P33076","url":"https://www.uniprot.org/uniprotkb/P33076/entry"},{"label":"NCBI Gene 4261","url":"https://www.ncbi.nlm.nih.gov/gene/4261"},{"label":"Ensembl ENSG00000179583","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000179583"},{"label":"Green et al., Blood 2010: selective 9p24.1 amplification and PD-1 ligand induction through JAK2 in Hodgkin lymphoma and mediastinal large B-cell lymphoma","url":"https://doi.org/10.1182/blood-2010-05-282780"},{"label":"Roemer et al., J Clin Oncol 2016: PD-L1 and PD-L2 genetic alterations in 108 classical Hodgkin lymphomas","url":"https://doi.org/10.1200/JCO.2016.66.4482"},{"label":"Steidl et al., Nature 2011: CIITA is a recurrent fusion partner in primary mediastinal B-cell lymphoma and classical Hodgkin lymphoma","url":"https://doi.org/10.1038/nature09754"},{"label":"Ansell et al., N Engl J Med 2015: nivolumab in relapsed or refractory Hodgkin lymphoma (23 patients)","url":"https://doi.org/10.1056/NEJMoa1411087"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["head-and-neck","skin-cancer","colorectal","lung-cancer","non-hodgkin-lymphoma","dlbcl","melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["pd1-checkpoint","jak-stat","antigen-presentation-immunoediting"],"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: IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; CIViC holds 1 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.","Lymphoma, 9p24.1 amplification of CD274, PDCD1LG2 and JAK2: The amplicon contains the genes for both PD-1 ligands and the kinase that induces them, so a single copy-number event raises the ligands twice over, by gene dose and by JAK2-driven transcription (Green 2010). It is the clearest example in oncology of a tumour genetically buying its way out of T-cell attack. Alongside it, CIITA, the master transactivator of MHC class II, is broken by recurrent fusions, which lowers class II on the tumour cell and, in the same rearrangements, places PD-L1 and PD-L2 under new promoters. Frequency: In 108 newly diagnosed classical Hodgkin lymphomas evaluated by fluorescence in situ hybridisation, 97% had concordant alterations of both loci: polysomy in 5% (5 of 108), copy gain in 56% (61 of 108) and amplification in 36% (39 of 108), and higher-level gain predicted shorter progression-free survival (Roemer 2016). Genomic CIITA breaks in 38% of primary mediastinal B-cell lymphomas and 15% of classical Hodgkin lymphomas across 263 B-cell lymphomas (Steidl 2011). What it changes about treatment: Yes, and it is the reason for the sharpest contrast in lymphoma immunotherapy. PD-1 blockade produced an objective response in 20 of 23 heavily pre-treated Hodgkin patients, 87%, in the first study, in a disease where most had already failed both transplant and brentuximab vedotin (Ansell 2015); in B-cell non-Hodgkin lymphoma outside the mediastinal group, single-agent checkpoint blockade does very little. Nothing is tested before a Hodgkin patient is given a checkpoint inhibitor, because the alteration is nearly universal."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"CIITA","role":["oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:7067","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7067","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P33076","url":"https://www.uniprot.org/uniprotkb/P33076/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene CIITA","url":"https://civicdb.org/features/3512","note":"1 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000179583","url":"https://platform.opentargets.org/target/ENSG00000179583/associations","note":"association with cancer (MONDO_0004992) 0.64; per-cancer scores at or above 0.5: colorectal cancer 0.52, melanoma 0.56, non-Hodgkin lymphoma 0.50, skin cancer 0.55, lung cancer 0.51 (GraphQL API, CC0)"},{"label":"IntOGen CIITA","url":"https://www.intogen.org/search?gene=CIITA","note":"driver in 3 cohorts (Act 2, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance), so the direction differs between cohorts but the alteration is somatic either way; 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 CIITA: RNA tissue enhanced (lymphoid tissue 50 nTPM); high antibody staining in 10 normal tissues; highest cancer staining lymphoma (9 of 12 high). Distribution: 5 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Head and neck squamous cell carcinoma, Skin cancer (all types), Colorectal cancer, Lung cancer (all types), 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 P33076","url":"https://www.uniprot.org/uniprotkb/P33076/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene CIITA","url":"https://civicdb.org/features/3512","note":"1 evidence items, 0 assertions, 1 variants; diseases: Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"IntOGen CIITA","url":"https://www.intogen.org/search?gene=CIITA","note":"driver in 3 cohorts (Act 2, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas CIITA tissue","url":"https://www.proteinatlas.org/ENSG00000179583-CIITA/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000179583 associations","url":"https://platform.opentargets.org/target/ENSG00000179583/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:7067","ensembl":"ENSG00000179583","uniprot":"P33076","entrez":"4261","firstDescribed":1993,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Steimle et al, Cell, 1993, \"Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or bare lymphocyte syndrome)\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8402893/","biology":"Essential for transcriptional activity of the HLA class II promoter; activation is via the proximal promoter. Does not bind DNA. May act in a coactivator-like fashion through protein-protein interactions by contacting factors binding to the proximal MHC class II promoter, to elements of the transcription machinery, or both PubMed:8402893, PubMed:7749984,. Alternatively it may activate HLA class II transcription by modifying proteins that bind to the MHC class II promoter. Also mediates enhanced MHC class I transcription; the promoter element requirements for CIITA-mediated transcription are distinct from those of constitutive MHC class I transcription, and CIITA can functionally replace TAF1 at these genes. Activates CD74 transcription. Location: Nucleus; Nucleus, PML body (UniProt). Locus 16p13.13 (HGNC).","whereFound":["Head and neck squamous cell carcinoma: IntOGen driver in 1 cohort (HNSC)","Skin cancer: Open Targets association 0.55 with skin cancer (MONDO_0002898)","Colorectal cancer: Open Targets association 0.52 with colorectal cancer (MONDO_0005575)","Lung cancer: Open Targets association 0.51 with lung cancer (MONDO_0008903)","Non-Hodgkin lymphoma: Open Targets association 0.50 with non-Hodgkin lymphoma (MONDO_0018908)","Diffuse large B-cell lymphoma: CIViC evidence names this disease; IntOGen driver in 2 cohorts (DLBCLNOS)"],"targetClass":"kinase","prevalence":[]},"route":"/targets/ciita/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin lymphoma","route":"/cancers/hodgkin-lymphoma/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"primary-mediastinal-b-cell-lymphoma","kind":"cancer","name":"Primary mediastinal (thymic) large B-cell lymphoma","route":"/cancers/primary-mediastinal-b-cell-lymphoma/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"pathway":[{"id":"antigen-presentation-immunoediting","kind":"pathway","name":"Antigen presentation & immune editing","route":"/pathways/antigen-presentation-immunoediting/"},{"id":"jak-stat","kind":"pathway","name":"JAK-STAT signalling","route":"/pathways/jak-stat/"},{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"}],"biomarker":[{"id":"pd-ligand-9p24-alteration","kind":"biomarker","name":"9p24.1 alteration of the PD-1 ligand loci","route":"/biomarkers/pd-ligand-9p24-alteration/"}]}}