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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 G12X HRAS G12S HRAS mutant HRAS act mut HRAS G12S |
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_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_176795.5 | 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_176795.4 | 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_005343.3 | 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 |
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 | 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 |