PPP6C

Overview

PPP6C encodes a serine/threonine phosphatase (Protein Phosphatase 6 Catalytic Subunit) implicated in DNA damage response and cell cycle regulation. PPP6C mutations have been identified as driver events in melanoma, associated with UV-induced mutagenesis.

Alterations observed in the corpus

  • PPP6C R264C mutation observed in a melanocyte from the control cohort (non-tanning individuals) in a study of molecular effects of indoor tanning; identified as one of multiple known melanoma driver gene mutations present in at-risk melanocytes PMID:38895302.
  • R264C and S270L hotspot mutations in 9% of melanomas (121-tumor Broad WES cohort); clustered near the catalytic-regulatory interface, suggesting gain-of-function alteration of phosphatase activity PMID:22817889
  • H92Y and R301C loss-of-function mutations in 12.4% of sun-exposed melanomas (147-tumor Yale WES cohort); found exclusively with BRAF or NRAS mutations PMID:22842228
  • In cutaneous melanoma (SKCM), PPP6C is a hot-spot significantly mutated gene (SMG) frequently co-occurring with RAS mutations; proposed as a target for Aurora kinase inhibitor combinations in RAS-mutant melanoma. PMID:26091043
  • R264C hotspot mutation in 2 desmoplastic melanoma tumors. PMID:26343386

Cancer types (linked)

  • Melanoma (MEL) — PPP6C R264C identified as a pathogenic mutation in a melanocyte clonal expansion study; co-occurring with other melanoma-associated driver mutations in the field PMID:38895302.

Co-occurrence and mutual exclusivity

  • PPP6C R264C was observed in the control (non-tanning) cohort melanocyte, suggesting UV-driven mutagenesis independent of indoor tanning exposure; field cancerization context with other driver mutations PMID:38895302.

Therapeutic relevance

  • Not directly therapeutically targeted in the corpus; PPP6C mutations may contribute to background melanoma risk in at-risk individuals.

Open questions

  • The role of PPP6C mutations in melanoma risk relative to other driver events (NF1, BRAF, RAC1) and their interaction with UV exposure patterns requires further characterization PMID:38895302.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:22817889

This page was processed by crosslinker on 2026-05-14. - PMID:22842228

This page was processed by crosslinker on 2026-05-14. - PMID:26091043

This page was processed by crosslinker on 2026-05-14. - PMID:26343386

This page was processed by wiki-cli on 2026-05-14.