NRAS G12S
Gene Variant Detail

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Gene NRAS
Variant G12S
Impact List missense
Protein Effect unknown
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 (PMID: 17823240), increased Stat5 phosphorylation in culture (PMID: 35211470), is transforming in one study (PMID: 17823240), but is not transforming in another study (PMID: 35211470), and therefore, its effect on Nras protein function is unknown.
Associated Drug Resistance
Category Variants Paths

NRAS mutant NRAS exon2 NRAS G12X NRAS G12S

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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_002524.5 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

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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