{"entity":{"id":"plcg1","kind":"target","name":"PLCG1","aka":["phospholipase C gamma 1","1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1","PLC148","PLC-II","PLCgamma1","NCKAP3","PLC1"],"tldr":"PLCG1 (1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Sarcomas, Renal cell carcinoma, Non-Hodgkin lymphoma and 5 more.","summary":"Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signalling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, EGFR, FGFR1, FGFR2, FGFR3 and FGFR4.\n\nCIViC holds 1 clinical evidence item and 0 assertions across 1 variant. Open Targets scores its association with cancer at 0.79 (direct and indirect evidence; datatypes literature 0.95, affected pathway 0.97, genetic association 0.17, somatic mutation 0.91). IntOGen calls it a driver in 4 cohorts (4 activating, 0 loss-of-function), covering Angiosarcoma, Low-Grade Glioma, NOS, Renal Cell Carcinoma, Soft Tissue.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:9065","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9065"},{"label":"UniProt P19174","url":"https://www.uniprot.org/uniprotkb/P19174/entry"},{"label":"NCBI Gene 5335","url":"https://www.ncbi.nlm.nih.gov/gene/5335"},{"label":"Ensembl ENSG00000124181","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000124181"},{"label":"Kataoka et al., Nat Genet 2015: integrated molecular analysis of 426 adult T-cell leukaemia/lymphoma cases","url":"https://doi.org/10.1038/ng.3415"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["sarcoma","rcc","non-hodgkin-lymphoma","skin-cancer","leukaemia","gastric","angiosarcoma","melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["oncogenic-viruses","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: IntOGen calls it an activating (Act) driver in 4 cohorts; 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.","Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Adult T-cell Leukaemia/lymphoma; Low-Grade Glioma, NOS.","Lymphoma, HTLV-1, Tax and HBZ: Human T-lymphotropic virus 1 integrates into the genome of a CD4 T cell and expresses Tax, which switches on NF-kB and interferes with the DNA-damage response and the spindle checkpoint, and HBZ, encoded on the opposite strand, which is retained when Tax expression is switched off under immune pressure. The host genome then acquires the rest of the lesions, and they are not random: the alterations found across 426 cases overlap significantly with the proteins Tax itself binds, and are concentrated in T-cell receptor and NF-kB signalling, T-cell trafficking and immune surveillance, with activating mutations in PLCG1, PRKCB, CARD11, VAV1, IRF4, FYN, CCR4 and CCR7, CTLA4-CD28 and ICOS-CD28 fusions, and intragenic deletions of IKZF2, CARD11 and TP73 (Kataoka 2015). Frequency: Across 426 adult T-cell leukaemia/lymphoma cases analysed by whole-genome, exome, transcriptome and targeted sequencing with copy-number and methylation arrays (Kataoka 2015). Most people infected with HTLV-1 never develop the disease, and the latency between infection, usually in infancy through breastfeeding, and the leukaemia is measured in decades. What it changes about treatment: The CCR4 finding is the practical one: CCR4 is both frequently expressed and frequently mutated, and mogamulizumab is used in this disease. The virus itself is not a drug target, and antiretroviral treatment does not cure the leukaemia."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"PLCG1","role":["oncogene-driver","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:9065","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9065","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P19174","url":"https://www.uniprot.org/uniprotkb/P19174/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene PLCG1","url":"https://civicdb.org/features/4326","note":"1 evidence items, 0 assertions, 1 variants; diseases: Adult T-cell Leukaemia/lymphoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000124181","url":"https://platform.opentargets.org/target/ENSG00000124181/associations","note":"association with cancer (MONDO_0004992) 0.79; per-cancer scores at or above 0.5: gastric cancer 0.50, melanoma 0.52, sarcoma 0.58, non-Hodgkin lymphoma 0.56, skin cancer 0.55, leukaemia 0.52 (GraphQL API, CC0)"},{"label":"IntOGen PLCG1","url":"https://www.intogen.org/search?gene=PLCG1","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 PLCG1: RNA low tissue specificity; blood lineage group enriched (NK-cells 3 nTPM, T-cells 6 nTPM); high antibody staining in 20 normal tissues; highest cancer staining testis cancer (12 of 12 high). Distribution: 6 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Sarcomas (soft tissue, bone, GIST), Renal cell carcinoma, Lymphoma, Skin cancer (all types), Leukaemia, Gastric & gastro-oesophageal junction cancer); 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 P19174","url":"https://www.uniprot.org/uniprotkb/P19174/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene PLCG1","url":"https://civicdb.org/features/4326","note":"1 evidence items, 0 assertions, 1 variants; diseases: Adult T-cell Leukaemia/lymphoma (GraphQL API, CC0)"},{"label":"IntOGen PLCG1","url":"https://www.intogen.org/search?gene=PLCG1","note":"driver in 4 cohorts (Act 4, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas PLCG1 tissue","url":"https://www.proteinatlas.org/ENSG00000124181-PLCG1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000124181 associations","url":"https://platform.opentargets.org/target/ENSG00000124181/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:9065","ensembl":"ENSG00000124181","uniprot":"P19174","entrez":"5335","firstDescribed":1990,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Burgess W.H. et al, Mol. Cell. Biol, 1990, \"Characterization and cDNA cloning of phospholipase C-gamma, a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2167438/","biology":"Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signalling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, EGFR, FGFR1, FGFR2, FGFR3 and FGFR4. Plays a role in actin reorganisation and cell migration. Guanine nucleotide exchange factor that binds the GTPase DNM1 and catalyses the dissociation of GDP, allowing a GTP molecule to bind in its place, therefore enhancing DNM1-dependent endocytosis. Location: Cell projection, lamellipodium; Cell projection, ruffle (UniProt). Locus 20q12 (HGNC).","whereFound":["Sarcomas: Open Targets association 0.58 with sarcoma (MONDO_0005089); IntOGen driver in 1 cohort (SOFT_TISSUE)","Renal cell carcinoma: IntOGen driver in 1 cohort (RCC)","Non-Hodgkin lymphoma: Open Targets association 0.56 with non-Hodgkin lymphoma (MONDO_0018908)","Skin cancer: Open Targets association 0.55 with skin cancer (MONDO_0002898)","Leukaemia: Open Targets association 0.52 with leukaemia (MONDO_0005059)","Gastric & gastro-oesophageal junction cancer: Open Targets association 0.50 with gastric cancer (MONDO_0001056)"],"targetClass":"oncogene","prevalence":[]},"route":"/targets/plcg1/","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":"angiosarcoma","kind":"cancer","name":"Angiosarcoma","route":"/cancers/angiosarcoma/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"leukaemia","kind":"cancer","name":"Leukaemia (all types)","route":"/cancers/leukaemia/"},{"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":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"pathway":[{"id":"inflammation-nfkb","kind":"pathway","name":"Inflammation & NF-κB","route":"/pathways/inflammation-nfkb/"},{"id":"oncogenic-viruses","kind":"pathway","name":"Oncogenic viruses","route":"/pathways/oncogenic-viruses/"}],"term":[{"id":"lymphoma-bio-htlv1","kind":"term","name":"HTLV-1, Tax and HBZ in adult T-cell leukaemia/lymphoma","route":"/terms/lymphoma-bio-htlv1/"}]}}