{"entity":{"id":"plcg2","kind":"target","name":"PLCG2","aka":["phospholipase C gamma 2","1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2"],"tldr":"PLCG2 (1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2) is an enzyme. The public catalogues list it as a drug target and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Chronic lymphocytic leukaemia.","summary":"The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. It is a crucial enzyme in transmembrane signalling.\n\nCIViC holds 3 clinical evidence items and 0 assertions across 3 variants, naming Venetoclax.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:9066","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9066"},{"label":"UniProt P16885","url":"https://www.uniprot.org/uniprotkb/P16885/entry"},{"label":"NCBI Gene 5336","url":"https://www.ncbi.nlm.nih.gov/gene/5336"},{"label":"Ensembl ENSG00000197943","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000197943"},{"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"],"cancers":["cll","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: CIViC lists 1 therapies; CIViC holds 3 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, 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":"PLCG2","role":["drug-target","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:9066","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9066","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P16885","url":"https://www.uniprot.org/uniprotkb/P16885/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene PLCG2","url":"https://civicdb.org/features/4327","note":"3 evidence items, 0 assertions, 3 variants; diseases: Chronic Lymphocytic Leukaemia (GraphQL API, CC0)"}],"distribution":"one-type","specificityNote":"Specificity not established: no corpus medicine is aimed at it and the catalogues give it only the roles drug-target, biomarker; HPA finds the RNA tissue enhanced, which says where the protein sits but not whether the tumour differs from normal tissue. HPA PLCG2: RNA tissue enhanced (lymphoid tissue 42 nTPM); high antibody staining in 8 normal tissues; highest cancer staining lymphoma (11 of 12 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Leukaemia); Open Targets associates it with 0 specific cancer types at or above 0.5. (No rule of scripts/fetch-target-specificity.ts fired.)","specificitySources":[{"label":"Human Protein Atlas PLCG2 tissue","url":"https://www.proteinatlas.org/ENSG00000197943-PLCG2/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000197943 associations","url":"https://platform.opentargets.org/target/ENSG00000197943/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:9066","ensembl":"ENSG00000197943","uniprot":"P16885","entrez":"5336","firstDescribed":1988,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Ohta et al, FEBS Lett, 1988, \"Complete cDNA encoding a putative phospholipase C from transformed human lymphocytes\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2849563/","biology":"The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. It is a crucial enzyme in transmembrane signalling. Location: Membrane raft (UniProt). Locus 16q24.1 (HGNC).","whereFound":["Chronic lymphocytic leukaemia: CIViC evidence names this disease"],"targetClass":"enzyme","prevalence":[]},"route":"/targets/plcg2/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"}],"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"mantle-cell-lymphoma","kind":"cancer","name":"Mantle cell lymphoma","route":"/cancers/mantle-cell-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"}],"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/"}],"biomarker":[{"id":"btk-c481s","kind":"biomarker","name":"BTK resistance mutations: C481S, and L528W and T474I after the non-covalent inhibitors","route":"/biomarkers/btk-c481s/"}],"term":[{"id":"btki-bcl2i-resistance-mutations","kind":"term","name":"BTK C481S, PLCG2 and BCL2 G101V resistance mutations","route":"/terms/btki-bcl2i-resistance-mutations/"}]}}