{"entity":{"id":"nras","kind":"target","name":"NRAS","aka":["N-ras","NRAS proto-oncogene, GTPase"],"tldr":"NRAS is one of the three RAS switch proteins that pass growth signals into the cell. When a mutation jams it on, as in a share of melanomas, the cell keeps dividing; today's drugs reach it indirectly through MEK or RAF, and pan-RAS inhibitors that bind the active form are in trials.","summary":"NRAS (chromosome 1p13.2) encodes a small GTPase of the RAS-MAPK pathway that binds GDP and GTP, hydrolyses GTP and relays signals for proliferation and survival; its turnover is controlled by LZTR1-directed ubiquitination through a CUL3 ligase complex (UniProt P01111). In OnCo, NRAS appears as the mutation that defines the melanoma population for the MEK inhibitor tunlametinib (approved in China in 2024 for NRAS-mutant melanoma, a group with no targeted therapy elsewhere) and for the pan-RAF inhibitor naporafenib studied with trametinib; as a resistance marker, with KRAS, that excludes patients from cetuximab in colorectal cancer and that the Tempus xT CDx companion diagnostic reports; and as one of the three isoforms the pan-RAS(ON) inhibitor JYP0015 binds, covering mutations at codons 12, 13, 61, 117 and 146.","asOf":"2026-09-22","links":[{"label":"HGNC HGNC:7989","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7989"},{"label":"UniProt P01111","url":"https://www.uniprot.org/uniprotkb/P01111/entry"},{"label":"NCBI Gene 4893","url":"https://www.ncbi.nlm.nih.gov/gene/4893"}],"tags":["wave5-target"],"related":["tunlametinib","naporafenib","cetuximab","tempus-xt-cdx","lenzilumab","kras","mek","nf1"],"cancers":["melanoma","colorectal","cmml"],"sections":[],"technologies":["kras-inhibitors"],"targets":[],"drugs":["jyp0015"],"companies":[],"institutions":[],"pathways":["ras-mapk","melanoma-signalling","colorectal-cancer-signalling"],"terms":["wild-type"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-douillard-prime-panitumumab-ras-nejm-2013"],"journals":[],"dependsOn":[],"notes":["Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.","Colorectal cancer: mutated in 4 to 9%, and unlike KRAS most of it sits outside exon 2: in crc_msk_2026 the missense records split 137 at codons 59 and 61 against 123 at codons 12 and 13, with Q61K the commonest single allele (cBioPortal). An exon 2-only assay therefore misses nearly all NRAS mutations, which is half the argument for extended RAS testing (Douillard 2013)."],"provenance":{"editedBy":"OnCo content wave 5 (HGNC REST, UniProt REST, corpus drug and pathway records)","editedOn":"2026-09-22"},"symbol":"NRAS","role":[],"sources":[],"specificity":"tumour-specific","distribution":"few-types","specificityNote":"Tumour-specific alteration: 1 of 1 medicines aimed at it name a mutant, fusion, exon or hotspot in their mechanism (JYP0015), an alteration absent from normal cells. HPA NRAS: RNA low tissue specificity; no normal tissue stained high; highest cancer staining ovarian cancer (2 of 9 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Skin cancer (all types), Colorectal cancer, Leukaemia); Open Targets associates it with 12 specific cancer types at or above 0.5 (large congenital melanocytic nevus, nevus, epidermal, acute myeloid leukemia, melanoma, autoimmune lymphoproliferative syndrome type 4, nevus and more). (Rule 4 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"ClinicalTrials.gov: trials of JYP0015","url":"https://clinicaltrials.gov/search?intr=JYP0015"},{"label":"Human Protein Atlas NRAS tissue","url":"https://www.proteinatlas.org/ENSG00000213281-NRAS/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000213281 associations","url":"https://platform.opentargets.org/target/ENSG00000213281/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:7989","ensembl":"ENSG00000213281","uniprot":"P01111","entrez":"4893","firstDescribed":1983,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Taparowsky et al, Cell, 1983, \"Structure and activation of the human N-ras gene\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/6616621/","biology":"RAS proteins share the GDP/GTP cycle and intrinsic GTPase activity; neurofibromin (NF1) stimulates that hydrolysis and so switches RAS off (UniProt P21359). Mutant NRAS stays GTP-bound, so the corpus drugs act below it (tunlametinib on MEK, naporafenib on RAF) or on the active state of all RAS isoforms (JYP0015). The lenzilumab record notes that chronic myelomonocytic leukaemia progenitors with NRAS, KRAS or CBL mutations proliferate in response to very low GM-CSF levels.","whereFound":["Melanoma with NRAS mutation (tunlametinib, naporafenib)","Colorectal cancer (RAS testing of KRAS and NRAS exons 2 to 4 before cetuximab; mutant tumours excluded)","Chronic myelomonocytic leukaemia progenitors (lenzilumab rationale)","Colorectal cancer: activating mutation (codon 12, 13, 59, 61 or 117) 4-9%"],"targetClass":"oncogene","prevalence":[{"cancerId":"colorectal","pct":"4-9","measure":"Activating mutation (codon 12, 13, 59, 61 or 117)","source":"https://www.cbioportal.org/study/summary?id=crc_msk_2026","note":"cBioPortal: 298 of 7,237, 4.1%, in crc_msk_2026; 46 of 1,134, 4.1%, in crc_msk_2017; 66 of 1,516, 4.4%, in crc_eo_2020; 33 of 534, 6.2%, in coadread_tcga_pan_can_atlas_2018; 20 of 224, 8.9%, in coadread_tcga_pub; 27 of 619, 4.4%, in coadread_dfci_2016; 24 of 1,015, 2.4%, in crc_sysucc_2022. NRAS runs the other way from KRAS on codon usage: in crc_msk_2026 the missense records split 137 at codons 59 and 61 against 123 at codons 12 and 13, with Q61K the single commonest allele (63 records), then G12D (54), Q61R (40) and Q61L (20) (cBioPortal)."}]},"route":"/targets/nras/","neighbours":{"drug":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},{"id":"jyp0015","kind":"drug","name":"JYP0015","route":"/drugs/jyp0015/"},{"id":"lenzilumab","kind":"drug","name":"Lenzilumab","route":"/drugs/lenzilumab/"},{"id":"naporafenib","kind":"drug","name":"Naporafenib","route":"/drugs/naporafenib/"},{"id":"tempus-xt-cdx","kind":"drug","name":"Tempus xT CDx","route":"/drugs/tempus-xt-cdx/"},{"id":"tunlametinib","kind":"drug","name":"Tunlametinib","route":"/drugs/tunlametinib/"}],"target":[{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"mek","kind":"target","name":"MEK1/2","route":"/targets/mek/"},{"id":"nf1","kind":"target","name":"NF1 (neurofibromin)","route":"/targets/nf1/"}],"cancer":[{"id":"cmml","kind":"cancer","name":"Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms","route":"/cancers/cmml/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"}],"technology":[{"id":"kras-inhibitors","kind":"technology","name":"KRAS & RAS inhibitors","route":"/technologies/kras-inhibitors/"}],"pathway":[{"id":"colorectal-cancer-signalling","kind":"pathway","name":"Colorectal cancer (KEGG map)","route":"/pathways/colorectal-cancer-signalling/"},{"id":"melanoma-signalling","kind":"pathway","name":"Melanoma (KEGG map)","route":"/pathways/melanoma-signalling/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"term":[{"id":"extended-ras-testing","kind":"term","name":"Extended RAS testing","route":"/terms/extended-ras-testing/"},{"id":"wild-type","kind":"term","name":"Wild-type (WT)","route":"/terms/wild-type/"}],"paper":[{"id":"paper-sepulveda-molecular-biomarkers-colorectal-guideline-jco-2017","kind":"paper","name":"Molecular biomarkers for the evaluation of colorectal cancer: guideline from ASCP, CAP, AMP and ASCO","route":"/key-papers/paper-sepulveda-molecular-biomarkers-colorectal-guideline-jco-2017/"},{"id":"paper-paradigm-jama-2023","kind":"paper","name":"Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer: A Randomized Clinical Trial","route":"/key-papers/paper-paradigm-jama-2023/"},{"id":"paper-douillard-prime-panitumumab-ras-nejm-2013","kind":"paper","name":"Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME)","route":"/key-papers/paper-douillard-prime-panitumumab-ras-nejm-2013/"},{"id":"paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017","kind":"paper","name":"Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials","route":"/key-papers/paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017/"},{"id":"paper-kris-lung-cancer-mutation-consortium-jama-2014","kind":"paper","name":"Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs","route":"/key-papers/paper-kris-lung-cancer-mutation-consortium-jama-2014/"}],"trial":[{"id":"chronos","kind":"trial","name":"CHRONOS","route":"/trials/chronos/"},{"id":"prime","kind":"trial","name":"PRIME","route":"/trials/prime/"}]}}