PLCG1

Overview

First described 1990. 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". Source.

Sources: HGNC HGNC:9065 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P19174 (protein name, function text, keywords and locations (REST API)); CIViC gene PLCG1 (1 evidence items, 0 assertions, 1 variants; diseases: Adult T-cell Leukaemia/lymphoma (GraphQL API, CC0)); Open Targets ENSG00000124181 (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)); IntOGen PLCG1 (driver in 4 cohorts (Act 4, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)

• 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.