NRAS

Chr 1

NRAS proto-oncogene, GTPase

Also known as: ALPS4, CMNS, N-ras, NCMS, NRAS1, NS6, RALD1

This is an N-ras oncogene encoding a membrane protein that shuttles between the Golgi apparatus and the plasma membrane. This shuttling is regulated through palmitoylation and depalmitoylation by the ZDHHC9-GOLGA7 complex. The encoded protein, which has intrinsic GTPase activity, is activated by a guanine nucleotide-exchange factor and inactivated by a GTPase activating protein. Mutations in this gene have been associated with somatic rectal cancer, follicular thyroid cancer, autoimmune lymphoproliferative syndrome, Noonan syndrome, and juvenile myelomonocytic leukemia. [provided by RefSeq, Jun 2011]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLeukemia, juvenile myelomonocytic
UniProtNoonan syndrome 6
UniProtRAS-associated autoimmune leukoproliferative disorder 1
UniProtMelanocytic nevus syndrome, congenital

Clinical highlights

Gene-disease validity (ClinGen)
Costello syndrome · ADLimitednot for standalone diagnostic reporting4 gene-disease associations curated in total
Interpreting a novel variant
Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.
12
Active trials
905
Pubs (1 yr)
P/LP submissions
P/LP missense
0.61
LOEUF
GOF*
Mechanism· G2P
📖
GeneReview available — NRAS
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.61LOEUF
pLI 0.490
Z-score 2.39
OE 0.19 (0.080.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.71Z-score
OE missense 0.53 (0.420.66)
55 obs / 104.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.19 (0.080.61)
00.351.4
Missense OE?0.53 (0.420.66)
00.61.4
Synonymous OE?1.00
01.21.6
LoF obs/exp: 2 / 10.3Missense obs/exp: 55 / 104.2Syn Z: 0.01

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.

VCEP specificationsRASopathyReleased
Specifications ↗Panel ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Non Small Cell Lung CancerEGFR Gene MutationALK Gene Mutation

Treatment Strategies and Survival Outcome for Non-small Cell Lung Cancer With Oncogenic Mutation

RECRUITING
NCT04322890Phase PHASE2Hunan Province Tumor HospitalStarted 2020-04-16
OsimertinibAlectinib 150 MGCrizotinib 250 MG
Melanoma

Effects of Anti-PD1 Adjuvant Checkpoint Blockade Immunotherapy on Atypical/Dysplastic Nevi

RECRUITING
NCT06599619John KirkwoodStarted 2025-02-20
Single agent, adjuvant anti-PD1 therapy
Non-small Cell Lung CancerHistiocytic NeoplasmHistiocytosis

Phase 1/2 Trial of S241656 in Selected RAS/MAPK Mutation- Positive Malignancies

RECRUITING
NCT05786924Phase PHASE1, PHASE2Institut de Recherches Internationales ServierStarted 2023-04-18
S241656FOLFOX6/FOLFOX7FOLFIRI
EGFR NP_005219.2:p.S492RKRAS Gene MutationMAP2K1 Gene Mutation

Panitumumab With or Without Trametinib in Treating Patients With Stage IV Colorectal Cancer

ACTIVE NOT RECRUITING
NCT03087071Phase PHASE2M.D. Anderson Cancer CenterStarted 2017-12-29
Laboratory Biomarker AnalysisPanitumumabTrametinib
Metastatic Colorectal Cancer (mCRC)Colorectal Neoplasms

Efficacy And Safety Of Hydroxychloroquine Combined With Methotrexate, Capecitabine And Bevacizumab Vs. Regorafenib In Participants With Refractory Metastatic Colorectal Cancer With Mutations In RAS Genes

RECRUITING
NCT06949982Phase PHASE2Sergey Orlov, MDStarted 2025-03-17
experimental group x-MAPRegorafenib (BAY 73-4506)
CRC (Colorectal Cancer)

PM8002 (BNT327) in Combination With Chemotherapy in Patients With Metastatic Colorectal Cancer

RECRUITING
NCT07133750Phase PHASE2Biotheus Inc.Started 2025-08-19
PM8002Chemotherapy Regimen 1Chemotherapy Regimen 2
Advanced LymphomaAdvanced Malignant Solid NeoplasmBladder Carcinoma

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ACTIVE NOT RECRUITING
NCT02465060Phase PHASE2National Cancer Institute (NCI)Started 2015-08-17
AdavosertibAfatinibAfatinib Dimaleate
Chronic Myelomonocytic Leukemia

Relevance of Peripheral Cells in the Pathophysiology of Chronic Myelomonocytic Leukemia (CMML)

RECRUITING
NCT03280888Centre Hospitalier Universitaire de NiceStarted 2014-11-05
Colorectal Cancer Metastatic

Exploration of Therapeutic Strategies for NeoRAS Wild-type Metastatic Colorectal Cancer Based on Circulating Tumor DNA

RECRUITING
NCT06440902Phase PHASE2Fudan UniversityStarted 2023-12-28
Cetuximab
Colorectal Cancer MetastaticBrain Metastases, AdultRas (KRAS or NRAS) Gene Mutation

Comparison of Molecular-Genetic Concordance of the Primary Tumor and Brain Metastases of Colorectal Cancer

RECRUITING
NCT06449989Blokhin's Russian Cancer Research CenterStarted 2024-04-01
Tumor samples will be tested for mutation status of KRAS, NRAS, BRAF, HER2 and MSI
NaeviNeurodevelopmental DisorderCongenital Nevus

CongenItal Naevus Cohort for Longitudinal Evaluation

RECRUITING
NCT06828822Phase NANantes University HospitalStarted 2025-07-23
Neurodevelopmental assessmentMeeting with the parentsPatient quality of life assessment
Colorectal Cancer

An 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 RECRUITING
NCT02394834TakedaStarted 2015-05-29
oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumaboxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, bevacizumab