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Gene | HRAS |
Variant | R135K |
Impact List | missense |
Protein Effect | unknown |
Gene Variant Descriptions | HRAS R135K does not lie within any known functional domains of the Hras protein (UniProt.org). R135K is predicted to disrupt the allosteric interaction within Hras by molecular dynamics simulation (PMID: 29072601), and results in decreased NS1 binding in the context of HRAS G12C, resulting in resistance to NS1, in cultured cells (PMID: 27820802) and leads to loss of binding to NS1 in cultured cells in another study (PMID: 36252024), but has not been fully biochemically characterized and therefore, its effect on Hras protein function is unknown. |
Associated Drug Resistance | Y |
Category Variants Paths |
HRAS mutant HRAS R135K |
Transcript | NM_005343.4 |
gDNA | chr11:g.533499_533500delCGinsAA |
cDNA | c.403_404delCGinsAA |
Protein | p.R135K |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_005343.3 | chr11:g.533499_533500delCGinsAA | c.403_404delCGinsAA | p.R135K | RefSeq | GRCh38/hg38 |
NM_176795.4 | chr11:g.533499_533500delCGinsAA | c.403_404delCGinsAA | p.R135K | RefSeq | GRCh38/hg38 |
NM_001130442.3 | chr11:g.533499_533500delCGinsAA | c.403_404delCGinsAA | p.R135K | RefSeq | GRCh38/hg38 |
NM_001130442.2 | chr11:g.533499_533500delCGinsAA | c.403_404delCGinsAA | p.R135K | RefSeq | GRCh38/hg38 |
NM_005343.4 | chr11:g.533499_533500delCGinsAA | c.403_404delCGinsAA | p.R135K | RefSeq | GRCh38/hg38 |
NM_176795.5 | chr11:g.533499_533500delCGinsAA | c.403_404delCGinsAA | p.R135K | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
HRAS G12V HRAS R135K | Advanced Solid Tumor | resistant | NS1 | Preclinical | Actionable | In a preclinical study, introducing HRAS R135K mutation in transformed cells expressing HRAS G12V resulted in reduced binding of Hras to NS1, leading to resistance to Mapk pathway inhibition in cell culture (PMID: 27820802). | 27820802 |