NF1
Chr 17ADSomaticneurofibromin 1
Also known as: NFNS, VRNF, WSS
The protein functions as a negative regulator of the RAS signal transduction pathway. Mutations cause neurofibromatosis type 1 and related conditions including Watson syndrome, neurofibromatosis-Noonan syndrome, and juvenile myelomonocytic leukemia through an autosomal dominant inheritance pattern. The pathogenic mechanism involves loss of function, leading to uncontrolled RAS signaling and subsequent tumor formation and developmental abnormalities.
No known disease relationship
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Extremely missense-constrained (top ~0.01%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
NF1 · 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
Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
RECRUITINGGene Therapy for Neurofibromatosis Type 2 (NF2) with ST002
NOT YET RECRUITINGPrevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History
NOT YET RECRUITINGA Study Evaluating the Activity of Anti-cancer Treatments Targeting Tumor Molecular Alterations/Characteristics in Advanced / Metastatic Tumors.
RECRUITINGRASopathy Biorepository
RECRUITINGFamilial Investigations of Childhood Cancer Predisposition
RECRUITINGTesting the Addition of Ipatasertib to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) for Stage III or IV Epithelial Ovarian Cancer
ACTIVE NOT RECRUITINGTesting Whether Cancers With Specific Mutations Respond Better to Glutaminase Inhibitor, Telaglenastat Hydrochloride, Anti-Cancer Treatment, BeGIN Study
ACTIVE NOT RECRUITINGNivolumab and Ipilimumab in Treating Patients With Rare Tumors
ACTIVE NOT RECRUITINGPASS of Paediatric Patients Initiating Selumetinib
ACTIVE NOT RECRUITINGDevelopment of Non-Invasive Prenatal Diagnosis for Single Gene Disorders
RECRUITINGNatural History Study of Cutaneous Neurofibromas in People With NF1
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools