GNAQ
Overview
GNAQ encodes a G-protein alpha subunit (Gq) that transduces signals from G-protein coupled receptors. Q209 hotspot mutations are the canonical driver in uveal melanoma, constitutively activating downstream MAPK and PI3K signaling. Rare GNAQ mutations have also been observed in cutaneous melanoma.
Alterations observed in the corpus
- Rare Q209 hotspot in Triple-WT cutaneous melanoma (typically a uveal-melanoma driver); co-occurs with SF3B1 R625H but not BAP1 mutations in this cutaneous cohort PMID:26091043
- Mutated in 8/28 uveal melanoma samples (7 p.Q209P, 1 p.G48L); mutually exclusive with GNA11; together GNAQ/GNA11 account for ~83% of UM drivers PMID:26683228
- GNAQ Q209P (uveal-melanoma hotspot) observed in one patient in a cohort of 180 advanced germ cell tumors profiled by MSK-IMPACT; listed as a potentially actionable alteration with MEK inhibitors nominated as candidate therapy PMID:27646943
Cancer types (linked)
- SKCM: Rare Q209 hotspot in the Triple-WT (non-BRAF/RAS/NF1) subtype of cutaneous melanoma; co-occurs with SF3B1 R625H PMID:26091043
Co-occurrence and mutual exclusivity
- Co-occurs with SF3B1 R625H but not BAP1 mutations in Triple-WT cutaneous melanoma; co-detected with GNA11 Q209 hotspots in the same subtype PMID:26091043
Therapeutic relevance
- GNAQ/GNA11-mutant tumors potentially targetable via downstream MAPK (MEK) inhibitors; no approved agent specifically for cutaneous GNAQ-mutant melanoma in the corpus.
Open questions
- Whether GNAQ Q209 hotspots in cutaneous melanoma represent a uveal-like molecular subtype with distinct biology and treatment response.
Sources
This page was processed by crosslinker on 2026-05-14. - PMID:26683228
This page was processed by crosslinker on 2026-05-14. - PMID:27646943
This page was processed by entity-page-writer on 2026-05-15.