Gene Variant Detail

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Gene NRAS
Variant G12C
Impact List missense
Protein Effect loss of function - predicted
Gene Variant Descriptions NRAS G12C is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). G12C has not been characterized, but can be predicted to confer a loss of function to the Nras protein based on the effects of HRAS G12C and KRAS G12C, which result in a loss of response to GTPase-activating proteins, and transformation of cultured cells (PMID: 26037647, PMID: 6092966).
Associated Drug Resistance
Category Variants Paths

NRAS mutant NRAS act mut NRAS G12C

NRAS mutant NRAS exon2 NRAS G12X NRAS G12C

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Transcript NM_002524.5
gDNA chr1:g.114716127C>A
cDNA c.34G>T
Protein p.G12C
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_002524.5 chr1:g.114716127C>A c.34G>T p.G12C RefSeq GRCh38/hg38
NM_002524 chr1:g.114716127C>A c.34G>T p.G12C RefSeq GRCh38/hg38
NM_002524.4 chr1:g.114716127C>A c.34G>T p.G12C RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
NRAS G12C rectum cancer predicted - sensitive Panitumumab + Sotorasib Case Reports/Case Series Actionable In a clinical case study, the combination of Lumakras (sotorasib) and Vectibix (panitumumab) resulted in a partial response after 12 weeks in a patient with metastatic rectal cancer harboring NRAS G12C (PMID: 37262393). 37262393
NRAS G12C Advanced Solid Tumor sensitive JDQ443 Preclinical - Cell culture Actionable In a preclinical study, JDQ443 inhibited viability of cultured cells expressing NRAS G12C (PMID: 38236605). 38236605
NRAS G12C Advanced Solid Tumor sensitive Sotorasib Preclinical - Cell culture Actionable In a preclinical study, Lumakras (sotorasib) inhibited viability of cultured cells expressing NRAS G12C (PMID: 38236605). 38236605
NRAS G12C colorectal cancer predicted - sensitive Panitumumab + Sotorasib Case Reports/Case Series Actionable In clinical case study, treatment with the combination of Lumakras (sotorasib) and Vectibix (panitumumab) resulted in a decrease in the size of liver metastases and improved serum markers after 2 months of treatment in a patient with colorectal cancer harboring NRAS G12C (PMID: 38236605). 38236605
NRAS G12C Advanced Solid Tumor sensitive RM-018 Preclinical - Cell culture Actionable In a preclinical study, RM-018 inhibited viability of cultured cells expressing NRAS G12C (PMID: 38236605). 38236605
NRAS G12C leukemia predicted - sensitive Sotorasib Preclinical - Biochemical Actionable In a preclinical study, Lumakras (sotorasib) inhibited downstream signaling in leukemia cells harboring NRAS G12C in culture (PMID: 38236605). 38236605