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Gene | NRAS |
Variant | G12S |
Impact List | missense |
Protein Effect | loss of function - predicted |
Gene Variant Descriptions | NRAS G12S is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G12S results in increased Erk phosphorylation and cell proliferation, is transforming in culture (PMID: 17823240), and is predicted to lead to a loss of Nras protein function based on the effects of HRAS G12S (PMID: 24224811, PMID: 21850009, PMID: 6330729). |
Associated Drug Resistance | |
Category Variants Paths |
NRAS mutant NRAS act mut NRAS G12S NRAS mutant NRAS exon2 NRAS G12X NRAS G12S |
Transcript | NM_002524.5 |
gDNA | chr1:g.114716127C>T |
cDNA | c.34G>A |
Protein | p.G12S |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_002524.4 | chr1:g.114716127C>T | c.34G>A | p.G12S | RefSeq | GRCh38/hg38 |
NM_002524 | chr1:g.114716127C>T | c.34G>A | p.G12S | RefSeq | GRCh38/hg38 |
NM_002524.5 | chr1:g.114716127C>T | c.34G>A | p.G12S | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
NRAS G12S | melanoma | predicted - sensitive | BGB3245 | Case Reports/Case Series | Actionable | In a Phase I trial, BGB3245 treatment demonstrated manageable safety and resulted in a disease control rate of 48% (16/33,1 complete response, 5 confirmed partial responses (PR), 2 unconfirmed PR, and 8 stable disease > 24 weeks) in patients with advanced solid tumors harboring MAPK pathway alterations, including a partial response in a patient with melanoma harboring NRAS G12S (Cancer Res (2023) 83 (8_Supplement): CT031). | detail... |
NRAS G12S | melanoma | predicted - sensitive | Tunlametinib | Case Reports/Case Series | Actionable | In a Phase I trial, Tunlametinib (HL-085) treatment demonstrated safety and preliminary efficacy in patients with advanced melanoma harboring NRAS mutations, resulting in a partial response in a patient harboring NRAS G12S who remained on treatment for 36 weeks (PMID: 36600247; NCT03973151). | 36600247 |
NRAS G12S | acute lymphoblastic leukemia | sensitive | IHMT-RAF-128 | Preclinical - Cell culture | Actionable | In a preclinical study, IHMT-RAF-128 inhibited proliferation in an acute lymphoblastic leukemia cell line harboring NRAS G12S in culture (PMID: 37164118). | 37164118 |