HRAS G12S - Gene Variant Detail

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Gene HRAS
Variant G12S
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions HRAS G12S does not lie within any known functional domains of the Hras protein (UniProt.org). G12S results in decreased Hras GTPase activity, loss of response to GTPase-activating proteins, leading to activation of downstream signaling pathways and transformation of cultured cells (PMID: 24224811, PMID: 21850009, PMID: 6330729).
Associated Drug Resistance
Category Variants Paths

HRAS mutant HRAS act mut HRAS G12S

HRAS mutant HRAS G12X HRAS G12S

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Transcript NM_005343.4
gDNA chr11:g.534289C>T
cDNA c.34G>A
Protein p.G12S
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_176795.4 chr11:g.534289C>T c.34G>A p.G12S RefSeq GRCh38/hg38
NM_001130442.2 chr11:g.534289C>T c.34G>A p.G12S RefSeq GRCh38/hg38
NM_005343 chr11:g.534289C>T c.34G>A p.G12S RefSeq GRCh38/hg38
NM_176795 chr11:g.534289C>T c.34G>A p.G12S RefSeq GRCh38/hg38
NM_001130442.3 chr11:g.534289C>T c.34G>A p.G12S RefSeq GRCh38/hg38
NM_005343.4 chr11:g.534289C>T c.34G>A p.G12S RefSeq GRCh38/hg38
NM_005343.3 chr11:g.534289C>T c.34G>A p.G12S RefSeq GRCh38/hg38
NM_001130442 chr11:g.534289C>T c.34G>A p.G12S RefSeq GRCh38/hg38
NM_176795.5 chr11:g.534289C>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
HRAS G12S head and neck squamous cell carcinoma predicted - sensitive Tipifarnib Case Reports/Case Series Actionable In a clinical case study, Zarnestra (tipifarnib) treatment resulted in a partial response that lasted for 8 months in a patient with ear canal squamous cell carcinoma harboring HRAS G12S (PMID: 38219706). 38219706
HRAS G12S head and neck squamous cell carcinoma predicted - sensitive Tipifarnib Preclinical - Pdx Actionable In a preclinical study, a head and neck squamous cell carcinoma patient-derived xenograft (PDX) model harboring HRAS G12S was sensitive to treatment with Zarnestra (tipifarnib), demonstrating inhibition of tumor growth, decreased cell proliferation, and reduced Erk activity (PMID: 32727882). 32727882
HRAS G12S renal pelvis transitional cell carcinoma predicted - sensitive Tipifarnib Case Reports/Case Series Actionable In a Phase II trial, Zarnestra (tipifarnib) demonstrated manageable toxicity profile, resulted in an objective response rate of 33.3% (5/15) in patients with transitional cell carcinoma harboring HRAS mutations, a patient with renal pelvis transitional cell carcinoma harboring HRAS G12S achieved a partial response (PMID: 32636318; NCT02535650). 32636318
HRAS G12S head and neck squamous cell carcinoma sensitive Alpelisib + Tipifarnib Preclinical - Pdx Actionable In a preclinical study, treatment with the combination of Piqray (alpelisib) and Zarnestra (tipifarnib) resulted in enhanced tumor growth inhibition compared to monotherapy in a patient-derived xenograft (PDX) model of head and neck squamous cell carcinoma harboring HRAS G12S (PMID: 38219706). 38219706
HRAS G12S lung squamous cell carcinoma sensitive Cisplatin + Pemetrexed Disodium + Trametinib Preclinical - Pdx Actionable In a preclinical study, the addition of Mekinist (trametinib) to treament with the combination of Alimta (pemetrexed disodium) and Platinol (cisplatin) resulted in improved tumor growth inhibition compared to chemotherapy or Mekinist (trametinib) alone in a patient-derived xenograft (PDX) model of squamous non-small cell lung cancer harboring HRAS G12S (PMID: 39199558). 39199558
HRAS G12S lung squamous cell carcinoma sensitive Buparlisib + Carboplatin + Paclitaxel Preclinical - Pdx Actionable In a preclinical study, the addition of Buparlisib (BKM120) to treatment with the combination of Paraplatin (carboplatin) and Taxol (paclitaxel) resulted in improved tumor growth inhibition compared to chemotherapy or Buparlisib (BKM120) alone in a patient-derived xenograft (PDX) model of squamous non-small cell lung cancer harboring HRAS G12S (PMID: 39199558). 39199558