HRAS G12X
Gene Variant Detail

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Gene HRAS
Variant G12X
Impact List missense
Protein Effect unknown
Gene Variant Descriptions HRAS G12X indicates any HRAS missense mutation that results in replacement of the glycine (G) at amino acid 12 by a different amino acid. HRAS G12 mutations are hotspot mutations that often result in decreased Hras GTPase activity, leading to activation of downstream signaling and transformation of cultured cells (PMID: 6092966, PMID: 24224811, PMID: 26985062).
Associated Drug Resistance
Category Variants Paths

HRAS mutant HRAS G12X

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Transcript NM_005343.4
gDNA chr11:g.534287_534289
cDNA c.34_36
Protein p.G12
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001130442 chr11:g.534287_534289 c.34_36 p.G12 RefSeq GRCh38/hg38
NM_176795.5 chr11:g.534287_534289 c.34_36 p.G12 RefSeq GRCh38/hg38
NM_176795 chr11:g.534287_534289 c.34_36 p.G12 RefSeq GRCh38/hg38
NM_005343.4 chr11:g.534287_534289 c.34_36 p.G12 RefSeq GRCh38/hg38
NM_005343 chr11:g.534287_534289 c.34_36 p.G12 RefSeq GRCh38/hg38
NM_001130442.3 chr11:g.534287_534289 c.34_36 p.G12 RefSeq GRCh38/hg38
NM_176795.4 chr11:g.534287_534289 c.34_36 p.G12 RefSeq GRCh38/hg38
NM_005343.3 chr11:g.534287_534289 c.34_36 p.G12 RefSeq GRCh38/hg38
NM_001130442.2 chr11:g.534287_534289 c.34_36 p.G12 RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
HRAS G12X pancreatic ductal adenocarcinoma sensitive Daraxonrasib Phase III Actionable In a Phase III trial (RASolute 302), treatment with Daraxonrasib (RMB-6236) in patients with metastatic pancreatic ductal adenocarcinoma significantly improved median overall survival (mOS, 13.2 vs 6.6 months, HR=0.40, p<0.001) and median progression-free survival (mPFS, 7.3 vs 3.5 months, HR=0.45, p<0.001) compared to chemotherapy in patients harboring RAS G12X, and mOS (13.2 vs 6.7 months, HR=0.40, p<0.001) and mPFS (7.2 vs 3.6 months, HR=0.49, p<0.001) in the overall cohort (PMID: 42223072; NCT06625320). 42223072