protein
Neurofibromin
Gene
NF1
Organism
Homo sapiens(9606)
Length
2839 aa
Mass
319,372 Da
# Neurofibromin Summary
Neurofibromin (NF1) is a large cytoplasmic protein that regulates Ras signaling by stimulating the GTPase activity of the Ras protein, thereby modulating its activation state (UniProt: P21359). The protein comprises 2,839 amino acids and serves as a negative regulator of the Ras pathway, a critical signaling cascade controlling cell proliferation and differentiation.
Loss-of-function mutations in NF1 cause neurofibromatosis type 1 (NF1), characterized by café-au-lait skin spots, iris Lisch nodules, and tumors of peripheral nerves with increased cancer susceptibility (UniProt: P21359). NF1 mutations also underlie related neurodevelopmental conditions including Watson syndrome—presenting with pulmonary stenosis, pigmentation abnormalities, and intellectual disability—and Neurofibromatosis-Noonan syndrome, which combines features of both NF1 and Noonan syndrome with motor delay and cardiac anomalies. Additional disease associations include juvenile myelomonocytic leukemia, familial spinal neurofibromatosis, and colorectal cancer predisposition.
NF1 is classified as a syndromic autism-spectrum risk gene by SFARI (SFARI Cat S), indicating that autism or developmental delay features appear as part of multi-system NF1-related presentations rather than as a primary phenotype of isolated mutations.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.440
P2
-0.133
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.2866 (2 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Genetic Evidence · ASD
Source: SFARI Gene database · gene.sfari.org
This protein is implicated in both ASD and Alzheimer's Disease. View all cross-disease proteins →
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Stimulates the GTPase activity of Ras. NF1 shows greater affinity for Ras GAP, but lower specific activity. May be a regulator of Ras activity
Disease associations
Neurofibromatosis 1NF1
A disease characterized by patches of skin pigmentation (cafe-au-lait spots), Lisch nodules of the iris, tumors in the peripheral nervous system and fibromatous skin tumors. Individuals with the disorder have increased susceptibility to the development of benign and malignant tumors.
Leukemia, juvenile myelomonocyticJMML
An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages.
Watson syndromeWTSN
A syndrome characterized by the presence of pulmonary stenosis, cafe-au-lait spots, and intellectual disability. It is considered as an atypical form of neurofibromatosis.
Familial spinal neurofibromatosisFSNF
Considered to be an alternative form of neurofibromatosis, showing multiple spinal tumors.
Neurofibromatosis-Noonan syndromeNFNS
Characterized by manifestations of both NF1 and Noonan syndrome (NS). NS is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis.
Colorectal cancerCRC
A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Sources
Last updated 5/8/2026, 1:09:18 AM