NRAS
Chr 1ADNRAS proto-oncogene, GTPase
Also known as: ALPS4, CMNS, N-ras, NCMS, NRAS1, NS6, RALD1
NRAS encodes a membrane-associated GTPase that shuttles between the Golgi apparatus and plasma membrane and functions in cellular signaling pathways. Germline mutations cause Noonan syndrome 6 with autosomal dominant inheritance, while somatic mutations result in various conditions including epidermal nevi, melanocytic nevus syndromes, and RAS-associated autoimmune lymphoproliferative syndrome. The gene is moderately constrained against loss-of-function variants (LOEUF 0.612), and both germline and somatic variants can affect multiple organ systems including cardiac, cutaneous, and hematologic.
Limited evidence — not for standalone diagnostic reporting
4 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
NRAS · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
CongenItal Naevus Cohort for Longitudinal Evaluation
RECRUITINGA Study to Investigate the Safety and Efficacy of NST-628 Oral Tablets in Subjects With Solid Tumors
RECRUITINGEfficacy And Safety Of Hydroxychloroquine Combined With Methotrexate, Capecitabine And Bevacizumab Vs. Regorafenib In Participants With Refractory Metastatic Colorectal Cancer With Mutations In RAS Genes
RECRUITINGPhase 1/2 Trial of S241656 in Selected RAS/MAPK Mutation- Positive Malignancies
RECRUITINGAn Exploratory Study of Treatment Sensitivity and Prognostic Factors in a Efficacy and Safety Study of mFOLFOX6 + Bevacizumab Versus mFOLFOX6 + Panitumumab Therapy in Patients With Chemotherapy-naïve Unresectable Advanced or Recurrent Colorectal Cancer
ACTIVE NOT RECRUITINGStudy of the Thyroid Function and Echostructural Morphology in Patients Affected With Rasopathies (ECORAS2023)
RECRUITINGTracking Mutations in Cell Free Tumour DNA to Predict Relapse in Early Colorectal Cancer
RECRUITINGTreatment Strategies and Survival Outcome for Non-small Cell Lung Cancer With Oncogenic Mutation
RECRUITINGCAnadian CAncers With Rare Molecular Alterations (CARMA) - Basket Real-world Observational Study (BROS)
RECRUITINGClinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tuspetinib (HM43239) in Patients With Relapsed or Refractory Acute Myeloid Leukemia
RECRUITINGMRI Simulation-guided Boost in Short-course Preoperative Radiotherapy for Unresectable Rectal Cancer
RECRUITINGEffects of Anti-PD1 Adjuvant Checkpoint Blockade Immunotherapy on Atypical/Dysplastic Nevi
RECRUITINGExternal Resources
Links to major genomics databases and tools