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Gene | HRAS |
Variant | A146T |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | HRAS A146T lies within the SAK motif of the Hras protein (PMID: 24224811). A146T does not affect Hras intrinsic GTPase activity, but results in increased nucleotide exchange rates, which leads to increase GTP-bound Hras, activation of downstream signaling, and senescence of cultured cells (PMID: 24224811, PMID: 21850009). |
Associated Drug Resistance | |
Category Variants Paths |
HRAS mutant HRAS act mut HRAS A146T |
Transcript | NM_005343.4 |
gDNA | chr11:g.533467C>T |
cDNA | c.436G>A |
Protein | p.A146T |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_005343.3 | chr11:g.533467C>T | c.436G>A | p.A146T | RefSeq | GRCh38/hg38 |
NM_001130442.2 | chr11:g.533467C>T | c.436G>A | p.A146T | RefSeq | GRCh38/hg38 |
NM_005343 | chr11:g.533467C>T | c.436G>A | p.A146T | RefSeq | GRCh38/hg38 |
NM_005343.4 | chr11:g.533467C>T | c.436G>A | p.A146T | RefSeq | GRCh38/hg38 |
NM_001130442 | chr11:g.533467C>T | c.436G>A | p.A146T | RefSeq | GRCh38/hg38 |
NM_001130442.3 | chr11:g.533467C>T | c.436G>A | p.A146T | RefSeq | GRCh38/hg38 |
NM_176795 | chr11:g.533467C>T | c.436G>A | p.A146T | RefSeq | GRCh38/hg38 |
NM_176795.4 | chr11:g.533467C>T | c.436G>A | p.A146T | RefSeq | GRCh38/hg38 |
NM_176795.5 | chr11:g.533467C>T | c.436G>A | p.A146T | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
HRAS A146T | 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 A146T was sensitive to treatment with Zarnestra (tipifarnib), demonstrating inhibition of tumor growth, decreased cell proliferation, and reduced Erk activity (PMID: 32727882). | 32727882 |