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Symbol NF1 contributors: mct - updated : 30-08-2016
HGNC name neurofibromin 1
HGNC id 7765
  • a nuclear localization signal
  • a cysteine and serine-rich domain/Ras-GTPase activating protein domain (CSRD/RasGAP)
  • a GRD and a putative upstream functional domain forming a cysteine/serine rich region
  • a potential ATP binding site
  • a SEC14 domain
  • three potential PRKA recognition sites
  • a C-terminal domain (CTD), regulating the metaphase to anaphase transition in a MAD2L1-independent fashion
    interspecies homolog to rattus Nf1 (98.62 pc)
    intraspecies homolog to Ras GTPase activating protein
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • GTPase activating protein, modulating cytoskeleton-mediated-processes
  • function as a negative regulator of Ras and required in endothelial cells but do not rule out a simultaneous requirement in the neural crest during cardiac development
  • regulator of RAS-induced signals in primary vascular smooth muscle cells
  • playing a critical role for normal histogenesis during embryologic development and wound healing
  • having a function in the modulation of excitability of sensory neurons
  • having an important role in the development of joints, as shown by fusion of the hip joints and other joint abnormalities and multiple essential roles in skeletal development and growth
  • plays a crucial role in modulating mesenchymal stem/progenitor cells differentiation into osteoblasts, and the defect in osteoblast differentiation may contribute at least in part to the osseous abnormalities seen in individuals with NF1
  • in inhibitory neurons regulates ERK-dependent phosphorylation of synapsin I and consequently GABA release
  • having a critical role in hypothalamic–pituitary axis function in a Ras-independent fashion
  • may function in the mammalian central nervous system (CNS) by modulating either Ras- or cAMP-dependent pathways
  • required for normal glial and neuronal development involving separable Ras-dependent and cAMP-dependent mechanisms
  • regulates activity-dependent GABA release in prefrontal cortex
  • important molecular regulator of interneuronal activity in the prefrontal cortex and striatum, brain regions critical for working memory performance
  • regulates neuroglial progenitor proliferation and glial differentiation in a brain region-specific manner
  • requirement of neurofibromin for muscle formation and maintenance
  • required for the control of MAPK signaling in various cell types, including cardiac and muscle cells
  • directly regulates osteoclastogenesis through MTOR signaling pathway
  • controls astrocyte growth in an AKT1-dependent, but TSC/RHEB-independent, fashion relevant to gliomagenesis
  • regulates CNS neurite length and growth cone areas in a cAMP/PKA/Rho/ROCK-dependent manner
  • regulatory role for NF1 during epicardial epithelial to mesenchymal transition (EMT)
  • by restraining RAS-ERK1/2 signaling, is a negative regulator of FGFR signaling in differentiating chondrocytes
  • is essential for normal muscle function and survival and are the first to suggest a direct link between NF1 and mitochondrial fatty acid metabolism
  • is the major RAS inactivator in dendritic spines
  • inactivates the oncoprotein RAS and plays important roles in nervous system development and learning
  • likely involved in the regulation of mechanical sensing, bone matrix composition and mechanical resistance of bone tissue
  • NF1 regulation of RAS/ERK signaling is required for appropriate granule neuron progenitor expansion and migration in cerebellar development
  • in prehypertrophic chondrocytes, downstream of FGFR1and FGFR3 and via an indirect mechanism, is required for normal extension and organization of proliferative columns
  • role for NF1 in the melanocyte lineage
  • differentially controls neural stem cell (NSC) proliferation and multilineage differentiation through the selective use of the PI3K/AKT1 and RAF/MEK pathways
  • during mitosis, is an integral part of the spindle, while its depletion leads to aberrant chromosome congression, possibly explaining the development of chromosomal instability in NF1
  • CELLULAR PROCESS cell cycle
    cell life, proliferation/growth
    cell organization/biogenesis
    cell migration & motility
    text organization of cytoskeleton during the formation of cellular contact
    signaling signal transduction
    RTK pathway
    a component
    small molecule
  • RAS (inhibitor of), GAP43, CDH13
  • interacting with the homodimer of SDC2
  • NF1 cooperates with BRAF mutations in melanoma
  • NF1 gene silencing induces upregulation of VEGFA expression in both Schwann and non-Schwann cells
  • DYNC1H1 interact with NF1 along microtubules in vesicular structures identified to be melanosomes and disruptions in the interaction may contribute to the abnormal pigmentary features commonly associated with NF1 disease
  • AKR1C2 (positive factor) and NF1 (negative factor), are the MTDH downstream players in the process of metastasis in liver cancer
  • SPRED1 has previously been demonstrated to interact with NF1 via its N-terminal Ena/VASP Homology 1 (EVH1) domain and to mediate membrane translocation of its target dependent on its C-terminal Sprouty domain
  • cell & other
    Other negatively regulated by FAF2
    corresponding disease(s) NF1 , NFNS , WATS , NFFS , NF1DEL
    related resource Neurofibromatosis Type I
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in NF1 tumor and juvenile myelomonocytic leukemia, in malignant peripheral nerve SHEAT tumors (MPNSTS) (early onset, poor prognosis), in melanoma desmoplastic ,neurotropic
    tumoral       loss of function
    in neurofibroma
    constitutional     --low  
    results in increased Ras activity and downstream MAPK/Akt signaling
    tumoral     --low  
    with ZNF423, in neuroblastomas with poor outcome
    tumoral somatic mutation      
    in gastrointestinal stromal tumors (GISTs)
    tumoral somatic mutation      
    in Desmoplastic Melanoma
    Variant & Polymorphism
    Candidate gene
    Therapy target
    mental retardationother 
    decrease GABA-mediated inhibition will be useful for treatment of the learning deficits associated with NF1
    inhibition of MAP2K1 signaling downstream of NF1 restores responsiveness to Retinoic acid (RA), suggesting a therapeutic strategy to overcome RA resistance in NF1-deficient neuroblastomas
    inhibiting MTOR may represent a viable strategy to treat NF1 bone diseases
  • mice lacking Nf1 in osteochondroprogenitor cells display skeletal dysplasia similar to patients with neurofibromatosis type I