PLCB3

Overview

PLCB3 encodes phospholipase C beta 3, a member of the phospholipase C family that hydrolyzes phosphatidylinositol 4,5-bisphosphate to generate inositol 1,4,5-trisphosphate and diacylglycerol, activating downstream signaling cascades. In cancer, PLCB3 is implicated in the GNAQ/GNA11/PLC signaling axis particularly in uveal melanoma, where Gαq/11 mutations constitutively activate PLCβ proteins.

Alterations observed in the corpus

  • Single p.K898N (c.G2694C) mutation in CTD linker domain in uveal melanoma; candidate for involvement in the GNAQ/GNA11/PLCB axis PMID:26683228

Cancer types (linked)

  • UVM (Uveal Melanoma): PLCB3 p.K898N identified as a candidate driver mutation within the GNAQ/GNA11 signaling pathway context PMID:26683228

Co-occurrence and mutual exclusivity

  • GNAQ and GNA11 mutations are the dominant upstream activators of PLCβ signaling in uveal melanoma; PLCB3 mutation may represent an alternative downstream activation route PMID:26683228

Therapeutic relevance

  • PLCB3 mutation may implicate the Gαq/PLCβ pathway as a therapeutic target in uveal melanoma, by analogy with PLCB4 hotspot mutations in the same pathway PMID:26683228

Open questions

  • Functional validation of PLCB3 p.K898N as a driver has not been performed; the mutation was flagged as a candidate but lacks experimental support PMID:26683228

Sources

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