{"entity":{"id":"prkcb","kind":"target","name":"PRKCB","aka":["protein kinase C beta","Protein kinase C beta type","PKCβ","PRKCB2","PRKCB1"],"tldr":"PRKCB (Protein kinase C beta type) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver and a biomarker, and an approved or late-stage drug is recorded against it. Tied to Leukaemia, Myeloproliferative neoplasms, Head and neck squamous cell carcinoma and 5 more.","summary":"Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signalling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'.\n\nCIViC holds 3 clinical evidence items and 0 assertions across 2 variants. Open Targets scores its association with cancer at 0.66 (direct and indirect evidence; datatypes literature 0.86, genetic association 0.00, somatic mutation 0.45, clinical 0.92). IntOGen calls it a driver in 4 cohorts (4 activating, 0 loss-of-function), covering Diffuse Large B-Cell Lymphoma, NOS, Head and Neck Squamous Cell Carcinoma, Prostate Adenocarcinoma, Stomach Adenocarcinoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:9395","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9395"},{"label":"UniProt P05771","url":"https://www.uniprot.org/uniprotkb/P05771/entry"},{"label":"NCBI Gene 5579","url":"https://www.ncbi.nlm.nih.gov/gene/5579"},{"label":"Ensembl ENSG00000166501","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000166501"},{"label":"Davis et al., Nature 2010: chronic active B-cell receptor signalling in diffuse large B-cell lymphoma","url":"https://doi.org/10.1038/nature08638"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["leukaemia","myeloproliferative-neoplasms","head-and-neck","prostate","gastric","systemic-mastocytosis","aml","dlbcl","non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["bcr-signalling","inflammation-nfkb"],"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: Open Targets known-drug datatype score 0.94; IntOGen calls it an activating (Act) driver in 4 cohorts; CIViC holds 3 clinical evidence items on its variants. Evidence tier \"approved-drug\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Adult T-cell Leukaemia/lymphoma.","Lymphoma, Chronic active B-cell receptor signalling, and BTK: The B-cell receptor normally signals only when it meets antigen. In activated B-cell-like lymphoma it signals continuously: the receptors cluster in the membrane and diffuse slowly, exactly as they do in an antigen-stimulated normal B cell, and knocking down IgM, Ig-kappa, CD79A, CD79B or BTK kills the cell. The signal runs CD79a/b to SYK to BTK to PLC-gamma-2 to protein kinase C beta to the CARD11-BCL10-MALT1 complex and into NF-kB. Mutations of the ITAM module of CD79B raise surface receptor expression and blunt LYN, the feedback brake (Davis 2010). Frequency: Mutations of the first ITAM tyrosine of CD79B in 18% of activated B-cell-like cases, frequent in that subtype and rare in other diffuse large B-cell lymphomas, absent from Burkitt and MALT lymphoma; activating CARD11 mutations in roughly 10% of activated B-cell-like cases (Davis 2010). What it changes about treatment: This is the one pathway in lymphoma where the biology picks the drug today. BTK inhibitors are standard in mantle cell lymphoma and Waldenstrom macroglobulinaemia and have activity in primary CNS lymphoma and in the MCD genetic subtype of diffuse large B-cell lymphoma; they do little in germinal-centre disease."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"PRKCB","role":["drug-target","oncogene-driver","biomarker"],"evidenceTier":"approved-drug","sources":[{"label":"HGNC HGNC:9395","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9395","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P05771","url":"https://www.uniprot.org/uniprotkb/P05771/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene PRKCB","url":"https://civicdb.org/features/4517","note":"3 evidence items, 0 assertions, 2 variants; diseases: Adult T-cell Leukaemia/lymphoma, Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000166501","url":"https://platform.opentargets.org/target/ENSG00000166501/associations","note":"association with cancer (MONDO_0004992) 0.66; per-cancer scores at or above 0.5: acute myeloid leukaemia 0.60, myeloproliferative neoplasm 0.60, systemic mastocytosis 0.54, leukaemia 0.65 (GraphQL API, CC0)"},{"label":"IntOGen PRKCB","url":"https://www.intogen.org/search?gene=PRKCB","note":"driver in 4 cohorts (Act 4, LoF 0); 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); 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 PRKCB: RNA tissue enhanced (brain 105 nTPM, lymphoid tissue 44 nTPM); high antibody staining in 3 normal tissues; highest cancer staining breast cancer (6 of 12 high). Distribution: 6 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Leukaemia, Myeloid neoplasms, Head and neck squamous cell carcinoma, Prostate cancer, Gastric & gastro-oesophageal junction cancer, Lymphoma); Open Targets associates it with 1 specific cancer type at or above 0.5 (acute myeloid leukemia). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P05771","url":"https://www.uniprot.org/uniprotkb/P05771/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene PRKCB","url":"https://civicdb.org/features/4517","note":"3 evidence items, 0 assertions, 2 variants; diseases: Adult T-cell Leukaemia/lymphoma, Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"IntOGen PRKCB","url":"https://www.intogen.org/search?gene=PRKCB","note":"driver in 4 cohorts (Act 4, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas PRKCB tissue","url":"https://www.proteinatlas.org/ENSG00000166501-PRKCB/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000166501 associations","url":"https://platform.opentargets.org/target/ENSG00000166501/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:9395","ensembl":"ENSG00000166501","uniprot":"P05771","entrez":"5579","firstDescribed":1986,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Coussens et al, Science, 1986, \"Multiple, distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/3755548/","biology":"Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signalling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signalling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localisation and in turn inhibition of BTK activity. Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Location: Cytoplasm; Nucleus; Membrane (UniProt). Locus 16p12.2-p12.1 (HGNC).","whereFound":["Leukaemia: Open Targets association 0.65 with leukaemia (MONDO_0005059)","Myeloproliferative neoplasms: Open Targets association 0.60 with myeloproliferative neoplasm (MONDO_0020076)","Head and neck squamous cell carcinoma: IntOGen driver in 1 cohort (HNSC)","Prostate cancer: IntOGen driver in 1 cohort (PRAD)","Gastric & gastro-oesophageal junction cancer: IntOGen driver in 1 cohort (STAD)","Systemic mastocytosis: Open Targets association 0.54 with systemic mastocytosis (MONDO_0016586)"],"targetClass":"kinase","prevalence":[]},"route":"/targets/prkcb/","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":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"id":"myeloproliferative-neoplasms","kind":"cancer","name":"Myeloproliferative neoplasms (PV, ET, myelofibrosis)","route":"/cancers/myeloproliferative-neoplasms/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"systemic-mastocytosis","kind":"cancer","name":"Systemic mastocytosis","route":"/cancers/systemic-mastocytosis/"}],"pathway":[{"id":"bcr-signalling","kind":"pathway","name":"B-cell receptor / BTK signalling (to NF-κB)","route":"/pathways/bcr-signalling/"},{"id":"inflammation-nfkb","kind":"pathway","name":"Inflammation & NF-κB","route":"/pathways/inflammation-nfkb/"}]}}