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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.
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.
In plain words · 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.
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.
RAS proteins share the GDP/GTP cycle and intrinsic GTPase activity; neurofibromin (NF1) stimulates that hydrolysis and so switches RAS off (UniProt P21359).
1 product aims at NRAS: small molecules. Drugs fit a pocket that exists only in one shape of the mutant protein and hold it there, off.
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.)
Sources: ClinicalTrials.gov: trials of JYP0015; Human Protein Atlas NRAS tissue; Open Targets ENSG00000213281 associations
First described 1983. Earliest sequence paper UniProt cites for the protein: Taparowsky et al, Cell, 1983, "Structure and activation of the human N-ras gene". Source.
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.
RNA: low tissue specificity, detected in all normal tissues.
No normal tissue stained high.
Medium only: carcinoid, endometrial cancer, head and neck cancer, liver cancer.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Colorectal cancer | 4-9% | Activating mutation (codon 12, 13, 59, 61 or 117) | 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). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
JYP0015 is an experimental small-molecule drug from Guangzhou JOYO Pharma in phase 2 trials for pancreatic ductal adenocarcinoma, non-small-cell lung cancer and colorectal cancer, aimed at KRAS.
This is the paper Europe PMC returns for registry id NCT02394795 with the most citations, so it is the natural first reading for anyone following the PARADIGM trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
It is the reference for what a colorectal molecular report must contain, and the document that turned extended RAS from a trial finding into a requirement.
The analysis that put 'left-sided, RAS and BRAF wild-type' into every guideline as the anti-EGFR population, and made an anatomical fact into a treatment-selection biomarker.
It is the study that made multiplex testing standard practice in lung adenocarcinoma, by showing both that most tumours have a driver and that finding it changes what patients receive.
Extended RAS testing (KRAS and NRAS exons 2, 3 and 4) became the standard before any EGFR antibody, and about one in six patients who would previously have been treated is now spared a drug that would have made things worse.
Query for this target: (TITLE:"NRAS" OR ABSTRACT:"NRAS" OR TITLE:"N-ras" OR ABSTRACT:"N-ras" OR TITLE:"NRAS proto-oncogene, GTPase" OR ABSTRACT:"NRAS proto-oncogene, GTPase") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about NRAS, not a curated reading list.
Shares KRAS & RAS inhibitors, RAS / RAF / MEK / ERK (MAPK), KRAS, Colorectal cancer and the tag wave5-target.
Shares Melanoma and the tag wave5-target.
Shares Melanoma and the tag wave5-target.
Shares Tempus xT CDx, Extended RAS testing, PRIME, Wild-type (WT).
Shares 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, PRIME, Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME), 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.
Shares Naporafenib, KRAS & RAS inhibitors, KRAS, Colorectal cancer.
Shares CHRONOS, Tempus xT CDx, PRIME, Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME).