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| Gene | NRAS |
| Variant | Q61K |
| Impact List | missense |
| Protein Effect | loss of function |
| Gene Variant Descriptions | NRAS Q61K is a hotspot mutation that lies within a GTP-binding region of the Nras protein (UniProt.org). Q61K confers a loss of function on Nras protein as indicated by activation of downstream pathway signaling, increased survival, and transformation of cultured cells (PMID: 22718121). |
| Associated Drug Resistance |
| Transcript | NM_002524 |
| gDNA | chr1:g.114713909G>T |
| cDNA | c.181C>A |
| Protein | p.Q61K |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_002524 | chr1:g.114713909G>T | c.181C>A | p.Q61K | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| NRAS Q61K | melanoma | predicted - sensitive | RAF709 | Preclinical - Cell culture | Actionable | In a preclinical study, RAF709 inhibited Erk signaling in melanoma cells harboring NRAS Q61K in culture (PMID: 29343524). | 29343524 |
| NRAS Q61K | lung non-small cell carcinoma | sensitive | Pimasertib + Regorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Stivarga (regorafenib) synergistically inhibited proliferation of non-small cell lung cancer cells harboring NRAS Q61K in culture (PMID: 23629727). | 23629727 |
| NRAS Q61K | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring NRAS Q61K were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). | 26343583 |
| NRAS Q61K | lung non-small cell carcinoma | sensitive | Pimasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) inhibited proliferation of non-small cell lung cancer cells harboring NRAS Q61K in culture (PMID: 23629727). | 23629727 |
| NRAS Q61K | lung non-small cell carcinoma | decreased response | Gedatolisib | Preclinical | Actionable | In a preclinical study, human non-small cell lung cancer cells harboring NRAS Q61K had a decreased response to Gedatolisib (PKI-587) in culture (PMID: 21325073, PMID: 12068308). | 21325073 12068308 |
| NRAS Q61K | melanoma | sensitive | Selumetinib | Preclinical | Actionable | In a preclinical study, Selumetinib (AZD6244) inhibited proliferation of human melanoma cell lines harboring NRAS Q61K in culture (PMID: 26343583). | 26343583 |
| NRAS Q61K | melanoma | sensitive | LY3009120 | Preclinical | Actionable | In a preclinical study, LY3009120 inhibited soft agar growth of human melanoma cancer cells harboring NRAS Q61K in culture (PMID: 26343583). | 26343583 |
| NRAS Q61K | 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 Q61K | lung non-small cell carcinoma | sensitive | Pimasertib + Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Nexavar (sorafenib) synergistically inhibited proliferation of non-small cell lung cancer cells harboring NRAS Q61K in culture (PMID: 23629727). | 23629727 |
| NRAS Q61K | lung cancer | sensitive | RAF709 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, RAF709 inhibited Erk signaling and proliferation of lung cancer cells harboring NRAS Q61K in culture, and resulted in tumor regression in cell line xenograft models (PMID: 29343524). | 29343524 |
| NRAS Q61K | lung non-small cell carcinoma | sensitive | Everolimus + Pimasertib | Preclinical - Cell culture | Actionable | In a preclinical study, Pimasertib (MSC1936369B) and Afinitor (everolimus) synergistically inhibited proliferation of non-small cell lung cancer cells harboring NRAS Q61K in culture (PMID: 23629727). | 23629727 |
| BRAF V600E NRAS Q61K | colorectal cancer | predicted - resistant | Panitumumab + Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with BRAF V600E colorectal cancer developed progressive disease after a partial response lasting 40 weeks to Vectibix (panitumumab) and Zelboraf (vemurafenib) combination treatment, NRAS Q61K was identified as an acquired mutation at the time of progression (PMID: 28951457). | 28951457 |
| BRAF V600E NRAS Q61K | melanoma | sensitive | XL888 | Preclinical | Actionable | In a preclinical study, treatment with XL888 resulted in increased apoptosis and decreased growth of Zelboraf (vemurafenib)-resistant melanoma cells harboring BRAF V600E along with NRAS Q61K in cell culture (PMID: 22351686). | 22351686 |
| BRAF V600E NRAS Q61K | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, a NRAS Q61K mutation conferred resistance to Zelboraf (vemurafenib) in melanoma cells harboring BRAF V600E in culture (PMID: 21107323). | 21107323 |
| BRAF V600E NRAS Q61K | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of melanoma cell lines harboring BRAF V600E and NRAS Q61K in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600E NRAS Q61K | lung adenocarcinoma | predicted - resistant | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a breast cancer patient with metastatic lung adenocarcinoma harboring BRAF V600E developed progressive disease after initial response to Talfinlar (dabrafenib) and Mekinist (trametinib) combination therapy, NRAS Q61K was identified as an acquired mutation after disease progression (PMID: 29631033). | 29631033 |
| BRAF V600E NRAS Q61K | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E expressing NRAS Q61K were resistant to Tafinlar (dabrafenib) mediated growth inhibition and retained MEK and ERK signaling (PMID: 22389471). | 22389471 |
| CDKN2A loss NRAS Q61K | melanoma | sensitive | SBI-0640756 | Preclinical | Actionable | In a preclinical study, SBI-0640726 delayed tumor growth of melanomas in mice with a genetic background of NRAS Q61K and CDKN2A loss (PMID: 26603897). | 26603897 |
| CDKN2A loss NRAS Q61K | melanoma | sensitive | Palbociclib + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Ibrance (palbociclib) and Mekinist (trametinib) induced tumor regression in a mouse melanoma model expressing NRAS Q61K and harboring CDKN2A loss (PMID: 22983396). | 22983396 |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | decreased response | GSK2126458 | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | sensitive | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | conflicting | Dabrafenib + GSK2126458 | Preclinical | Actionable | In a preclinical study, the response of human melanoma cell lines harboring BRAF V600E, NRAS Q61K, and MAP2K1 P387S to Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) was conflicting as one cell line with this mutation profile responded to the combination and another cell line with the mutation profile did not (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | decreased response | Trametinib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were >20-fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring BRAF V600E, NRAS Q61K and MAP2K1 P387S were resistant to growth inhibition by Zelboraf (vemurafenib) in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant to growth inhibition by Mekinist (trametinib) in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | sensitive | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S were resistant Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, A146T and MAP2K1 P387S were resistant to Zelboraf (vemurafenib) growth inhibition in culture (PMID: 22389471). | 22389471 |
| BRAF V600E MAP2K1 P387S NRAS Q61K NRAS A146T | melanoma | decreased response | GSK2126458 | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600E, NRAS Q61K, NRAS A146T and MAP2K1 P387S had reduced sensitivity to Omipalisib (GSK2126458) in comparison to parental cell lines harboring BRAF V600E in culture (PMID: 22389471). | 22389471 |
| BRAF V600K NRAS Q61K | melanoma | decreased response | Trametinib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600K and NRAS Q61K were 3-7 fold less sensitive to growth inhibition by Mekinist (trametinib) than parental cell lines harboring BRAF V600K in culture (PMID: 22389471). | 22389471 |
| BRAF V600K NRAS Q61K | melanoma | sensitive | GSK2126458 + Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition in melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture, compared to either agent alone (PMID: 22389471). | 22389471 |
| BRAF V600K NRAS Q61K | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) in combination with Mekinist (trametinib) inhibited growth of melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture (PMID: 22389471). | 22389471 |
| BRAF V600K NRAS Q61K | melanoma | sensitive | Dabrafenib + GSK2126458 | Preclinical | Actionable | In a preclinical study, Tafinlar (dabrafenib) in combination with Omipalisib (GSK2126458) resulted in improved growth inhibition of human melanoma cell lines harboring BRAF V600K and NRAS Q61K in culture (PMID: 22389471). | 22389471 |
| BRAF V600K NRAS Q61K | melanoma | sensitive | GSK2126458 | Preclinical | Actionable | In a preclinical study, Omipalisib (GSK2126458) inhibited the growth of melanoma cell lines harboring BRAF V600K in culture (PMID: 22389471). | 22389471 |
| BRAF V600K NRAS Q61K | melanoma | resistant | Dabrafenib | Preclinical | Actionable | In a preclinical study, melanoma cell lines harboring BRAF V600K and NRAS Q61K were resistant to Tafinlar (dabrafenib) growth inhibition in culture (PMID: 22389471). | 22389471 |
| BRAF V600E NRAS Q61K NRAS A146T | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical | Actionable | In a preclinical study, Talfinlar (dabrafenib) in combination with Mekinist (trametinib) resulted in improved growth inhibition of human melanoma cells harboring BRAF V600E and NRAS A146T and NRAS Q61K in culture (PMID: 22389471). | 22389471 |
| BRAF G469R NRAS Q61K | melanoma | sensitive | LY3009120 | Preclinical | Actionable | In a preclinical study, LY3009120 inhibited soft agar growth of human melanoma cancer cells harboring BRAF G469R and NRAS Q61K in culture (PMID: 26343583). | 26343583 |
| BRAF G469R NRAS Q61K | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cells harboring BRAF G469R and NRAS G61K were insensitive to Zelboraf (vemurafenib) in culture (PMID: 26343583). | 26343583 |
| BRAF G469R NRAS Q61K | melanoma | decreased response | Selumetinib | Preclinical | Actionable | In a preclinical study, Selumetinib (AZD6244) modestly inhibited proliferation of human melanoma cells harboring BRAF G469R and NRAS Q61K in culture (PMID: 26343583). | 26343583 |
| BRAF V600X BRAF amp NRAS Q61K | melanoma | resistant | Vemurafenib | Clinical Study - Cohort | Actionable | In a clinical study, a melanoma patient harboring a BRAF V600 mutation developed resistant mutations, BRAF amplification and NRAS Q61K, during treatment with Zelboraf (vemurafenib) (PMID: 24265153). | 24265153 |
| BRAF wild-type NRAS Q61K | melanoma | resistant | GDC0879 | Preclinical - Pdx | Actionable | In a preclinical study, GDC0879 failed to inhibit growth of BRAF wild-type melanoma cells harboring NRAS Q61K in patient-derived xenograft models (PMID: 19276360). | 19276360 |
| BRAF L597V NRAS Q61K | lung non-small cell carcinoma | decreased response | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K demonstrated decreased sensitivity to Zelboraf (vemurafenib) in culture (PMID: 27523909). | 27523909 |
| BRAF L597V NRAS Q61K | lung non-small cell carcinoma | decreased response | PLX7904 | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61L demonstrated decreased sensitivity to PLX7904 in culture (PMID: 27523909). | 27523909 |
| BRAF L597V NRAS Q61K | lung non-small cell carcinoma | sensitive | TAK-632 | Preclinical - Cell culture | Actionable | In a preclinical study, TAK-632 inhibited proliferation of non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K in culture (PMID: 27523909). | 27523909 |
| BRAF L597V NRAS Q61K | lung non-small cell carcinoma | decreased response | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K demonstrated decreased sensitivity to Tafinlar (dabrafenib) in culture (PMID: 27523909). | 27523909 |
| BRAF L597V NRAS Q61K | lung non-small cell carcinoma | sensitive | AZ628 | Preclinical - Cell culture | Actionable | In a preclinical study, AZ628 inhibited proliferation of non-small cell lung cancer cells harboring both BRAF L597V and NRAS Q61K in culture (PMID: 27523909). | 27523909 |
| BRAF G466V NRAS Q61K | lung non-small cell carcinoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) growth of a non-small cell lung cancer cell line harboring BRAF G466V and expressing NRAS Q61K in culture (PMID: 28783719). | 28783719 |
| BRAF G469V NRAS Q61K | melanoma | no benefit | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Tafinlar (dabrafenib) treatment did not result in significant growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). | 29903896 |
| BRAF G469V NRAS Q61K | melanoma | predicted - resistant | Trametinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Zelboraf (vemurafenib) to treatment with Mekinist (trametinib) resulted in increased proliferation compared to Mekinist (trametinib) alone in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). | 29903896 |
| BRAF G469V NRAS Q61K | melanoma | sensitive | Binimetinib + Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mektovi (binimetinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). | 29903896 |
| BRAF G469V NRAS Q61K | melanoma | sensitive | Encorafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). | 29903896 |
| BRAF G469V NRAS Q61K | melanoma | sensitive | LY3009120 | Preclinical - Cell culture | Actionable | In a preclinical study, LY3009120 inhibited growth of a melanoma cell line harboring BRAF G469V and NRAS Q61K in culture (PMID: 29903896). | 29903896 |
| NRAS Q61K NRAS mut | melanoma | decreased response | Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61K demonstrated a decreased response to treatment with Ibrance (palbociclib) in culture compared to control (PMID: 30819666). | 30819666 |
| NRAS Q61K NRAS mut | melanoma | predicted - resistant | Palbociclib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61K demonstrated resistance to the combination treatment of Mekinist (trametinib) and Ibrance (palbociclib) in culture (PMID: 30819666). | 30819666 |
| NRAS Q61K NRAS mut | melanoma | predicted - resistant | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cells expressing NRAS Q61K demonstrated resistance to treatment with Mekinist (trametinib) in culture (PMID: 30819666). | 30819666 |