NF1 Gene (Neurofibromin 1): Function, Mutations, and Associated Diseases
A comprehensive biomedical overview of the NF1 gene, its protein product neurofibromin, associated disorders, expression patterns, and mutation landscape.
Gene Information Card
| Symbol | NF1 |
|---|---|
| Full Name | neurofibromin 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q11.2 |
| NCBI Gene ID | 4763 ncbi.nlm.nih.gov/gene/4763 |
| Ensembl ID | ENSG00000196712 |
| UniProt ID | P21359 |
| OMIM ID | 613113 |
| HGNC ID | 7765 |
| Aliases | NFNS, VRNF, WSS, neurofibromatosis-related protein |
Description
The NF1 gene encodes neurofibromin, a large cytoplasmic protein that functions as a GTPase-activating protein (GAP) for RAS. It negatively regulates RAS signaling by accelerating the hydrolysis of RAS-bound GTP to GDP, thereby suppressing cell proliferation and survival. Loss of NF1 function leads to constitutive RAS activation, contributing to tumorigenesis and neurodevelopmental disorders. NF1 is a classic tumor suppressor gene, and germline mutations cause neurofibromatosis type 1 (NF1), an autosomal dominant disorder characterized by café-au-lait spots, neurofibromas, and increased cancer risk.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurofibromatosis type 1 (NF1) | Loss-of-function mutations in NF1 lead to reduced neurofibromin activity, causing uncontrolled RAS signaling in Schwann cells and melanocytes, resulting in benign tumors (neurofibromas) and pigmentary lesions. | OMIM #162200; ClinVar; NCBI Gene |
| Juvenile myelomonocytic leukemia (JMML) | Somatic or germline NF1 mutations in hematopoietic cells cause RAS hyperactivation, promoting myeloid proliferation. | COSMIC; ClinVar; OMIM #607785 |
| Breast cancer | Somatic NF1 mutations or loss of heterozygosity contribute to tumor progression via RAS/MAPK pathway activation. | COSMIC; ClinVar; NCBI Gene |
| Glioblastoma | NF1 alterations (mutations, deletions) are frequent in glioblastoma, driving tumor growth through RAS signaling. | COSMIC; ClinVar; NCBI Gene |
| Neurofibrosarcoma (malignant peripheral nerve sheath tumor) | Biallelic inactivation of NF1 in neurofibromas leads to malignant transformation. | OMIM; COSMIC; ClinVar |
| Astrocytoma | NF1 loss contributes to low-grade astrocytoma development in NF1 patients. | OMIM; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.4 | Medium |
| Adipose tissue | 8.7 | Low |
| Lung | 7.9 | Low |
| Spleen | 6.5 | Low |
| Testis | 5.8 | Low |
| Kidney | 4.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression in embryonic kidney cells |
| K562 | 10.1 | Moderate expression in leukemia cells |
| MCF7 | 8.3 | Moderate expression in breast cancer cells |
| HeLa | 7.6 | Moderate expression in cervical cancer cells |
| A549 | 6.9 | Low expression in lung cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2970_2972del (p.Phe990del) | Deletion | Rare | Loss of function; disrupts GAP domain, leading to RAS activation |
| c.3827G>A (p.Arg1276Gln) | Missense | Rare | Loss of function; affects GAP activity |
| c.2033dup (p.Gln679Profs*18) | Frameshift | Rare | Loss of function; premature truncation |
| c.1466A>G (p.Tyr489Cys) | Missense | Rare | Loss of function; reduced protein stability |
| c.574C>T (p.Arg192*) | Nonsense | Rare | Loss of function; premature stop codon |
Mutation functional classification
Loss of Function (LOF)
Most NF1 mutations are loss-of-function, including nonsense, frameshift, splice-site, and missense mutations that impair neurofibromin's GAP activity or protein stability. This leads to RAS hyperactivation and tumorigenesis.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NF1; it is a tumor suppressor, and loss of function is the primary mechanism.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with dimerization or interacting partners, but this is not well established. Most NF1 mutations act via haploinsufficiency or loss of heterozygosity.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • RAS GTPase binding |
| • Protein binding | • Signal transduction |
| • Negative regulation of cell proliferation | • Regulation of small GTPase mediated signal transduction |
| • Neurogenesis | • Cytoplasm |
| • Cytoskeleton | • Membrane |
Pathways
• RAS/MAPK signaling pathway
• PI3K/AKT signaling pathway
• mTOR signaling pathway
• Neurotrophin signaling pathway
• ErbB signaling pathway
• Regulation of actin cytoskeleton
Protein Summary
Neurofibromin is a 2818-amino acid protein with a central GAP-related domain (GRD) that accelerates GTP hydrolysis on RAS. It also contains domains for lipid binding, tubulin binding, and interaction with other proteins. Neurofibromin is widely expressed, with highest levels in the nervous system. It regulates cell growth, differentiation, and survival. Mutations in NF1 cause neurofibromatosis type 1 and predispose to various cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NF1 Knockout HEK293 Cell Line | EDJ-KQ204 | Human | 4763 | Details Get a Quote |
| NF1 Knockout A-549 Cell Line | EDJ-KQ19318 | Human | 4763 | Details Get a Quote |
| NF1 Knockout HCT 116 Cell Line | EDJ-KQ19319 | Human | 4763 | Details Get a Quote |
| NF1 Knockout HeLa Cell Line | EDJ-KQ19320 | Human | 4763 | Details Get a Quote |
| NF1 (p.P678=) Point Mutation in HAP1 Cell Line | EDC03561 | Human | 4763 | Details Get a Quote |
| NF1 (c.4836-20502C>A )Point Mutation in HAP1 Cell Line | EDC03562 | Human | 4763 | Details Get a Quote |
