Gene Variant Detail

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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

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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_176795.5 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_001130442 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_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

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 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 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 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 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 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 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 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