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Gene | HRAS |
Variant | Q61L |
Impact List | missense |
Protein Effect | loss of function |
Gene Variant Descriptions | HRAS Q61L does not lie within any known functional domains of the Hras protein (UniProt.org). Q61L results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 23487764, PMID: 3510078). |
Associated Drug Resistance | |
Category Variants Paths |
HRAS mutant HRAS act mut HRAS Q61L HRAS mutant HRAS Q61X HRAS Q61L |
Transcript | NM_005343.4 |
gDNA | chr11:g.533874T>A |
cDNA | c.182A>T |
Protein | p.Q61L |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_005343.3 | chr11:g.533874T>A | c.182A>T | p.Q61L | RefSeq | GRCh38/hg38 |
NM_001130442.2 | chr11:g.533874T>A | c.182A>T | p.Q61L | RefSeq | GRCh38/hg38 |
NM_001130442.3 | chr11:g.533874T>A | c.182A>T | p.Q61L | RefSeq | GRCh38/hg38 |
NM_005343 | chr11:g.533874T>A | c.182A>T | p.Q61L | RefSeq | GRCh38/hg38 |
NM_176795 | chr11:g.533874T>A | c.182A>T | p.Q61L | RefSeq | GRCh38/hg38 |
NM_176795.4 | chr11:g.533874T>A | c.182A>T | p.Q61L | RefSeq | GRCh38/hg38 |
NM_005343.4 | chr11:g.533874T>A | c.182A>T | p.Q61L | RefSeq | GRCh38/hg38 |
NM_001130442 | chr11:g.533874T>A | c.182A>T | p.Q61L | RefSeq | GRCh38/hg38 |
NM_176795.5 | chr11:g.533874T>A | c.182A>T | p.Q61L | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
HRAS Q61L | lung squamous cell carcinoma | no benefit | Buparlisib | Preclinical - Cell culture | Actionable | In a preclinical study, BKM120 did not inhibit growth of a lung squamous cell carcinoma cell line harboring HRAS Q61L in culture (PMID: 26544513) | 26544513 |
HRAS Q61L | Advanced Solid Tumor | sensitive | Everolimus | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing HRAS Q61L demonstrated sensitivity to growth inhibition by Afinitor (everolimus) in culture (PMID: 26544513). | 26544513 |
HRAS Q61L | Advanced Solid Tumor | sensitive | Binimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing HRAS Q61L demonstrated sensitivity to growth inhibition by Binimetinib (MEK162) in culture (PMID: 26544513). | 26544513 |
HRAS Q61L | lung squamous cell carcinoma | sensitive | Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Selumetinib (AZD6244) inhibited growth of a lung squamous cell carcinoma cell line harboring HRAS Q61L in culture, and inhibited tumor growth in xenograft models (PMID: 26544513). | 26544513 |
HRAS Q61L | head and neck squamous cell carcinoma | predicted - sensitive | Tipifarnib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a head and neck squamous cell carcinoma cell line xenograft model harboring HRAS Q61L was sensitive to treatment with Zarnestra (tipifarnib), demonstrating inhibition of tumor growth and vessel formation, increased apoptotic activity, and decreased cell proliferation (PMID: 32727882). | 32727882 |
HRAS Q61L | head and neck squamous cell carcinoma | sensitive | Sirolimus + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Rapamune (sirolimus) worked synergistically with Mekinist (trametinib) to inhibit proliferation of head and neck squamous carcinoma cell lines harboring HRAS Q61L in culture and to reduce tumor growth in cell line xenograft models (PMID: 26882569). | 26882569 |
HRAS Q61L | skin squamous cell carcinoma | no benefit | PLX7904 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX7904 did not stimulate growth of Zelboraf (vemurafenib)-induced cutaneous squamous cell carcinoma cells harboring HRAS Q61L in culture or in cell line xenograft models (PMID: 26466569). | 26466569 |
HRAS Q61L | lung squamous cell carcinoma | sensitive | Everolimus + Selumetinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Selumetinib (AZD6244) and Afinitor (everolimus) inhibited growth of a lung squamous cell carcinoma cell line harboring HRAS Q61L in culture, and inhibited tumor growth in xenograft models, with increased efficacy compared to either agent alone (PMID: 26544513). | 26544513 |
HRAS Q61L | lung squamous cell carcinoma | sensitive | Binimetinib + Everolimus | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Binimetinib (MEK162) and Afinitor (everolimus) reduced phosphorylation of ERK and S6 and worked synergistically to inhibit growth of a lung squamous cell carcinoma cell line harboring HRAS Q61L in culture (PMID: 26544513). | 26544513 |
HRAS Q61L | Advanced Solid Tumor | sensitive | Binimetinib + Everolimus | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Binimetinib (MEK162) and Afinitor (everolimus) worked synergistically to inhibit growth of transformed cells expressing HRAS Q61L in culture (PMID: 26544513). | 26544513 |
HRAS Q61L | lung squamous cell carcinoma | sensitive | AZD8055 + Binimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Binimetinib (MEK162) and AZD8055 reduced phosphorylation of ERK and S6 and worked synergistically to inhibit growth of a lung squamous cell carcinoma cell line harboring HRAS Q61L in culture (PMID: 26544513). | 26544513 |
HRAS Q61L | Advanced Solid Tumor | sensitive | NS1 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing HRAS Q61L demonstrated sensitivity to NS1, resulting in inhibition of Mapk and Akt signaling and cell transformation in culture (PMID: 27820802). | 27820802 |
HRAS Q61L | head and neck squamous cell carcinoma | sensitive | SCH772984 + Tipifarnib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of SCH772984 sensitized head and neck squamous cell carcinoma cell lines harboring HRAS Q61L to treatment with Zarnestra (tipifarnib), resulting in enhanced growth inhibition and increased apoptosis in culture (PMID: 35247914). | 35247914 |
HRAS Q61L | head and neck squamous cell carcinoma | sensitive | Tipifarnib + Ulixertinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination treatment with Ulixertinib (BVD-523) and Zarnestra (tipifarnib) resulted in a synergistic effect, with enhanced apoptosis in a head and neck squamous cell carcinoma cell line harboring HRAS Q61L in culture (PMID: 35247914). | 35247914 |
HRAS Q61L | esophageal cancer | sensitive | IHMT-RAF-128 | Preclinical - Cell culture | Actionable | In a preclinical study, IHMT-RAF-128 inhibited proliferation in an esophageal cancer cell line harboring HRAS Q61L in culture (PMID: 37164118). | 37164118 |