Gene Variant Detail

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Gene NRAS
Variant Q61R
Impact List missense
Protein Effect loss of function - predicted
Gene Variant Descriptions NRAS Q61R is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). Q61R results in increased GTP-bound Nras, which leads to activation of Mapk signaling and cell transformation in culture (PMID: 16818621, PMID: 34117033), and is predicted to lead to a loss of GTPase activity based on the effect of HRAS Q61R (PMID: 3510078).
Associated Drug Resistance
Category Variants Paths

NRAS mutant NRAS act mut NRAS Q61R

NRAS mutant NRAS exon3 NRAS Q61X NRAS Q61R

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Transcript NM_002524.5
gDNA chr1:g.114713908T>C
cDNA c.182A>G
Protein p.Q61R
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_002524.4 chr1:g.114713908T>C c.182A>G p.Q61R RefSeq GRCh38/hg38
NM_002524.5 chr1:g.114713908T>C c.182A>G p.Q61R RefSeq GRCh38/hg38
NM_002524 chr1:g.114713908T>C c.182A>G p.Q61R RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
NRAS Q61R thyroid cancer sensitive MK2206 Preclinical - Cell culture Actionable In a preclinical study, MK2206 inhibited AKT activation, proliferation, and growth of thyroid cancer cell lines with PI3K/AKT pathway alterations in culture, including an anaplastic thyroid cancer cell line harboring NRAS Q61R (PMID: 21289267). 21289267
NRAS Q61R melanoma sensitive Binimetinib Phase II Actionable In a Phase II trial, Binimetinib (MEK162) treatment resulted in partial response in 20% (6/30), and stable disease in 43% (13/30) of melanoma patients harboring NRAS mutations, including Q61L (1/30), Q61K (9/30), and Q61R (15/30) (PMID: 23414587). 23414587
NRAS Q61R melanoma sensitive Chelidonine Preclinical - Cell line xenograft Actionable In a preclinical study, Chelidonine treatment inhibited activation of Nras and downstream signaling pathways, reduced proliferation and colony formation, and induced apoptosis in melanoma cells harboring NRAS Q61R in culture, and inhibited tumor growth and increased survival in a cell line xenograft model (PMID: 32156748). 32156748
NRAS Q61R melanoma predicted - sensitive LY3009120 Preclinical - Cell culture Actionable In a preclinical study, LY3009120 treatment inhibited Erk activation and reduced proliferation of melanoma cells harboring NRAS Q61R and wild-type RAF in culture (PMID: 30559419). 30559419
NRAS Q61R melanoma predicted - sensitive BGB659 Preclinical - Cell culture Actionable In a preclinical study, BGB659 treatment inhibited Erk activation and reduced proliferation of melanoma cells harboring NRAS Q61R and wild-type RAF in culture (PMID: 30559419). 30559419
NRAS Q61R melanoma predicted - sensitive TAK-632 Preclinical - Cell culture Actionable In a preclinical study, TAK-632 treatment inhibited Erk activation and reduced proliferation of melanoma cells harboring NRAS Q61R and wild-type RAF in culture, but at a higher concentration than was required to inhibit melanoma cells harboring BRAF V600E (PMID: 30559419). 30559419
NRAS Q61R melanoma resistant PLX8394 Preclinical - Cell culture Actionable In a preclinical study, melanoma cells harboring NRAS Q61R demonstrated resistance to PLX8394 treatment in culture (PMID: 30559419). 30559419
NRAS Q61R melanoma sensitive Chloroquine + Trametinib Preclinical - Pdx Actionable In a preclinical study, combination treatment with Mekinist (trametinib) and Chloroquine resulted in tumor regression in a melanoma patient-derived xenograft (PDX) model harboring NRAS Q61R (PMID: 30833748). 30833748
NRAS Q61R melanoma sensitive Lifirafenib + Trametinib Preclinical - Pdx Actionable In a preclinical study, the combination treatment of Mekinist (trametinib) and Lifirafenib (BGB-283) resulted in durable tumor regression compared to stabilized tumor growth when treated with either agent alone in patient-derived xenograft (PDX) models of melanoma harboring NRAS Q61R (PMID: 33318037). 33318037
NRAS Q61R melanoma decreased response Lifirafenib + SCH772984 Preclinical - Cell culture Actionable In a preclinical study, the combination treatment of Lifirafenib (BGB-283) and SCH772984 in Mekinist (trametinib)-resistant melanoma cells harboring NRAS Q61R in culture resulted in a decreased response compared to the combination treatment with Lifirafenib (BGB-283) and Mekinist (trametinib), demonstrating reduced inhibition of cell growth (PMID: 33318037). 33318037
NRAS Q61R melanoma sensitive Binimetinib + RAF709 Preclinical - Cell culture Actionable In a preclinical study, the combination of Mektovi (binimetinib) and RAF709 resulted in inhibition of cell growth in a MEK inhibitor-resistant melanoma cell line harboring NRAS Q61R (PMID: 33318037). 33318037
NRAS Q61R ameloblastoma predicted - sensitive Binimetinib Case Reports/Case Series Actionable In a Phase II trial (MATCH), Mektovi (binimetinib) treatment resulted in a partial response in a patient with metastatic malignant ameloblastoma harboring NRAS Q61R, and the patient stayed on treatment for 26 months (PMID: 33637626; NCT02465060). 33637626
NRAS Q61R colorectal cancer predicted - sensitive Binimetinib Case Reports/Case Series Actionable In a Phase II trial (MATCH), Mektovi (binimetinib) treatment resulted in an unconfirmed partial response in a patient with colorectal cancer harboring NRAS Q61R, with a 48.2% tumor reduction at cycle 4, but the disease progressed at cycle 7 (PMID: 33637626; NCT02465060). 33637626
NRAS Q61R Advanced Solid Tumor sensitive Belvarafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing NRAS Q61R were sensitive to treatment with Belvarafenib (HM95573) in culture, demonstrating decreased cell viability (PMID: 33953400). 33953400
NRAS Q61R melanoma predicted - sensitive Belvarafenib Case Reports/Case Series Actionable In a Phase I trial, Belvarafenib (HM95573) treatment in a melanoma patient harboring NRAS Q61R led to a tumor reduction of 84% after 24 weeks of treatment and a confirmed partial response at 12 weeks, and response to treatment was maintained for 40 weeks (PMID: 33953400; NCT03118817). 33953400
NRAS Q61R acute biphenotypic leukemia no benefit Trametinib Case Reports/Case Series Actionable In a clinical study, Mekinist (trametinib) treatment was well tolerated and led to an initial decrease of peripheral blasts in a pediatric patient with mixed phenotype acute leukemia harboring NRAS Q61R who had previously undergone a stem cell transplant, but patient experienced progressive disease after 2 months, and died soon after (PMID: 33563661; NCT02670525). 33563661
NRAS Q61R melanoma sensitive ERAS-007 Preclinical - Cell culture Actionable In a preclinical study, ERAS-007 (ASN007) treatment inhibited proliferation of a melanoma cell line harboring NRAS Q61R in culture (PMID: 34337566). 34337566
NRAS Q61R melanoma sensitive ASTX029 Preclinical - Cell line xenograft Actionable In a preclinical study, ASTX029 treatment inhibited growth of melanoma cell lines harboring NRAS Q61R in culture, and inhibited tumor growth in cell line xenograft models (PMID: 34330842). 34330842
NRAS Q61R urinary bladder cancer sensitive RAF265 Preclinical - Cell culture Actionable In a preclinical study, RAF265 treatment decreased viability of a bladder cancer cell line harboring NRAS Q61R in culture (PMID: 34554931). 34554931
NRAS Q61R urinary bladder cancer sensitive Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Mekinist (trametinib) treatment decreased tumor weight of a cell line xenograft model of bladder cancer harboring NRAS Q61R (PMID: 34554931). 34554931
NRAS Q61R urinary bladder cancer sensitive RAF265 + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, RAF265 and Mekinist (trametinib) combination treatment decreased Erk1/2 phosphorylation in cultured cells and decreased tumor volume and weight of a cell line xenograft model harboring NRAS Q61R (PMID: 34554931). 34554931
NRAS Q61R urinary bladder cancer sensitive LXH 254 Preclinical - Cell line xenograft Actionable In a preclinical study, LXH 254 treatment decreased Mek signaling, colony formation and viability, and increased apoptosis in a bladder cancer cell line harboring NRAS Q61R in culture and decreased tumor weight and volume in a cell line xenograft model (PMID: 34554931). 34554931
NRAS Q61R urinary bladder cancer sensitive LXH 254 + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, LXH 254 and Mekinist (trametinib) combination treatment decreased tumor volume and weight compared to vehicle in a cell line xenograft model of bladder cancer harboring NRAS Q61R (PMID: 34554931). 34554931
NRAS Q61R melanoma predicted - sensitive IMM-1-104 Preclinical - Cell line xenograft Actionable In a preclinical study, IMM-1-104 treatment led to tumor growth regression in a cell line xenograft model of melanoma harboring NRAS Q61R (Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P252). detail...
NRAS Q61R melanoma sensitive PD-0325901 Preclinical - Cell culture Actionable In a preclinical study, PD-0325901 treatment induced cell cycle arrest and inhibited growth of melanoma cells harboring NRAS Q61R in culture (PMID: 25422890). 25422890
NRAS Q61R melanoma sensitive RO5126766 Preclinical - Cell line xenograft Actionable In a preclinical study, RO5126766 (VS-6766) treatment induced cell cycle arrest, decreased Mek and Erk phosphorylation, and inhibited growth of melanoma cells harboring NRAS Q61R in culture, and inhibited tumor growth in cell line xenograft models (PMID: 25422890). 25422890
NRAS Q61R melanoma predicted - sensitive Tunlametinib Case Reports/Case Series Actionable In a Phase I trial, Tunlametinib (HL-085) treatment demonstrated safety and preliminary efficacy in patients with advanced melanoma harboring NRAS mutations, resulting in an objective response rate of 37.5% (3/8), a disease control rate of 75% (6/8), and a median progression-free survival of 114.0 days in patients harboring NRAS Q61R at the recommended Phase II dose (PMID: 36600247; NCT03973151). 36600247
NRAS Q61R melanoma predicted - sensitive Tunlametinib Case Reports/Case Series Actionable In a Phase II trial, Tunlametinib (HL-085) treatment resulted in a confirmed objective response rate of 35.8% (34/95, all partial responses), a median progression-free survival of 4.2 months, disease control rate of 72.6% (69/95), median duration of response of 6.1 months, and median overall survival of 13.7 months in Chinese patients with advanced melanoma harboring NRAS mutations including NRAS Q61R (40%), Q61K (29.5%), and G12D (9.5%) (PMID: 38479118; NCT05217303). 38479118
NRAS Q61R melanoma predicted - sensitive PHI-501 Preclinical - Cell culture Actionable In a preclinical study, PHI-501 inhibited growth and migration and induced apoptosis in a melanoma cell line harboring NRAS Q61R in culture (Cancer Res (2023) 83 (7_Supplement): 1627). detail...
NRAS Q61R ameloblastoma sensitive GDC-0623 Preclinical - Cell culture Actionable In a preclinical study, GDC-0623 inhibited Erk phosphorylation and viability of an ameloblastoma cell line harboring NRAS Q61R in culture (PMID: 35689405). 35689405
NRAS Q61R melanoma sensitive NST-628 Preclinical - Cell line xenograft Actionable In a preclinical study, NST-628 inhibited viability of a melanoma cancer cell line harboring NRAS Q61R in culture and induced tumor regression in an intracranial cell line xenograft model (PMID: 38588399). 38588399
NRAS Q61R ovarian cancer predicted - sensitive Navitoclax + Trametinib Case Reports/Case Series Actionable In a Phase I/II trial, treatment with the combination of Navitoclax (ABT-263) and Mekinist (trametinib) resulted in a partial response rate of 33.3% (7/21) amongst efficacy evaluable patients with gynecologic cancers harboring mutations in KRAS or NRAS, including a partial response in a patient with ovarian cancer harboring NRAS Q61R (PMID: 38456660; NCT02079740). 38456660
NRAS Q61R gastrointestinal neuroendocrine tumor sensitive Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Mekinist (trametinib) inhibited viability, proliferation, and migration of a cell line derived from a pediatric gastroenteropancreatic neuroendocrine-like tumor patient-derived xenograft (PDX) model harboring NRAS Q61R in culture and inhibited tumor growth and increased survival compared to treatment with vehicle in a patient-derived xenograft (PDX) cell line model (PMID: 38959709). 38959709