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Symbol NF1 contributors: mct - updated : 19-05-2012
HGNC name neurofibromin 1
HGNC id 7765
TYPE functioning gene
SPECIAL FEATURE opposite orientation
  • EVIA, EVIB, OGMP, embedded in intron 27b (see symbols)
  • a NF1 RNA editing C>U in the GRD domain resulting in a truncated form
  • STRUCTURE 282.70 kb     58 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure a cryptic exon situated between exons 4a and 4b, inserted in the NF1 mRNA after a cold shock, also a mRNA editing site in exon 23 creating an in-frame codon stop
    MAPPING cloned Y linked Y status confirmed
    Map cen - D17S841 - D17S975 - D17S1549 - D17S1294 - SLC6A4 - CPD CPD - D17S2009 - D17S2004 - D17S2120 - NF1 NF1 - D17S1800 - D17S798 - D17S54 - D17S933 - D17S946 - qter
    Physical map
    KIAA1361 17q11.2 serine/threonine protein kinase TAO1 homolog LOC116236 17q11.2 hypothetical protein LOC116236 LOC90313 17q11.2 hypothetical protein BC004507 GIT1 17p11.2 G protein-coupled receptor kinase-interactor 1 FLJ25555 17q11.2 hypothetical protein FLJ25555 FLJ14871 17q11.2 hypothetical protein FLJ14871 SSH2 17q11.2 slingshot 2 FLJ46247 17q11.2 FLJ46247 protein DKFZP434K1421 17q11.2 hypothetical protein DKFZp434K1421 SLC6A4 17q11.2 solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 BLMH 17q11.2 bleomycin hydrolase LOC388364 17 similar to AWKS9372 CPD 17q11.2 carboxypeptidase D GOSR1 17q11.2 golgi SNAP receptor complex member 1 LOC390784 17 similar to Arachidonate 12-lipoxygenase, 12S-type (12-LOX) (Platelet-type lipoxygenase 12) LOC388365 17 LOC388365 DKFZP434O047 17q11.2 DKFZP434O047 protein LOC284089 17q11.2 similar to keratin 17 LOC388366 17 LOC388366 DKFZp667M2411 17q11.2 hypothetical protein DKFZp667M2411 LOC388367 17 similar to Joined to JAZF1 CRLF3 17q11.2 cytokine receptor-like factor 3 FLJ12735 17q11.2 cytokine receptor-like factor 3 FLJ22729  hypothetical protein FLJ22729 CENTA2 17q11.2 centaurin, alpha 2 RNF135 17q11.2 ring finger protein 135 NF1 17q11.2 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) OMG 17q11.2 oligodendrocyte myelin glycoprotein EVI2B 17q11.2 ecotropic viral integration site 2B EVI2A 17q11.2 ecotropic viral integration site 2A AK3P1 17q11.2 adenylate kinase 3 pseudogene 1 RAB11-FIP4  rab11-family interacting protein 4 LOC339281 17q11.2 hypothetical LOC339281 HSA272196 17q11.2 hypothetical protein, clone 2746033 HCA66 17q11.2 hepatocellular carcinoma-associated antigen 66 JJAZ1 17q11.2 hepatocellular carcinoma-associated antigen 66 LOC114659  KIAA0563-related gene LOC390785 17 hypothetical gene supported by NM_019613 ARHT1 17q11.2-q12 ras homolog gene family, member T1 RHBDL4 17q11.2 rhomboid, veinlet-like 4 (Drosophila) NJMU-R1 17q12 protein kinase Njmu-R1 ZNF207 17q11.2 zinc finger protein 207 PSMD11 17q12 proteasome (prosome, macropain) 26S subunit, non-ATPase, 11 CDK5R1 17p11.2-q11 cyclin-dependent kinase 5, regulatory subunit 1 (p35) MYO1D 19p13.3-p13.2 myosin ID
    TRANSCRIPTS type messenger
    text at least four alternatively spliced transcripts, four exons with alternative splicing, exon 9a, 10a-2, 23a, 48a
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    - splicing - - - Schwann cells 2006 16813595
  • also called NF1 II or GRD2
  • insertion of exon 23a
  • reduced capacity of acting as GAP
  • essential role for the normal brain function
  • - splicing - - - in muscle, cardiac and skeleton 2006 16813595
  • also called NF1 3 or 3-prime ALT
  • containing exon 48a
  • - splicing - - - in muscle, cardiac and skeleton 2006 16813595
  • also called NF1 4
  • containing both exons 23a and 48a
  • - splicing - - - limited neuronal expression 2006 16813595
  • also called NF1 9a or 9br
  • inclusion of exon 9a
  • involved in the learning and memory mechanisms
  • - splicing - - - ubiquitous 2006 16813595
  • also called NF1 10a-2
  • insertion of the alternative exon 10a-2
  • introducing a trans membrane domain, and function in the endoplasmic reticulum
  • 57 - 12331 316.9 2818 - 2008 18503770
  • variant 2
  • lacking an in-frame exon, compared to variant 1
  • 58 - 12394 319 2839 - 2008 18503770
    variant 1
    15 - 2889 - 593 - 2008 18503770
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouth   moderately
     salivary gland   highly
    Endocrineparathyroid   highly
     thyroid   highly
    Hearing/Equilibriumear   highly
    Lymphoid/Immunethymus   moderately
    Reproductivemale systemtestis  highly
    Respiratoryrespiratory tractlarynx  moderately
    Urinarybladder   highly
    Visualeye   moderately
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  moderately
    Nervouscentral  highly
    SystemCellPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
    physiological period fetal, pregnancy
    Text developmental and tissue specific regulation of expression
  • a nuclear localization signal
  • GTPase activating (GAP) related domain (RASGAP domain)
  • 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
    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
  • 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
  • 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
    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