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    NF1 neurofibromin 1 [ Homo sapiens (human) ]

    Gene ID: 4763, updated on 27-Nov-2024

    Summary

    Official Symbol
    NF1provided by HGNC
    Official Full Name
    neurofibromin 1provided by HGNC
    Primary source
    HGNC:HGNC:7765
    See related
    Ensembl:ENSG00000196712 MIM:613113; AllianceGenome:HGNC:7765
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    WSS; NFNS; VRNF
    Summary
    This gene product appears to function as a negative regulator of the ras signal transduction pathway. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The mRNA for this gene is subject to RNA editing (CGA>UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in thyroid (RPKM 9.3), brain (RPKM 8.2) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See NF1 in Genome Data Viewer
    Location:
    17q11.2
    Exon count:
    58
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (31094927..31377677)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (32040661..32323039)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (29421945..29704695)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124903974 Neighboring gene NF1 (neurofibromin 1) promoter region Neighboring gene ReSE screen-validated silencer GRCh37_chr17:29430681-29430862 Neighboring gene MIR4733 host gene Neighboring gene microRNA 4733 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr17:29471062-29471656 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr17:29471657-29472252 Neighboring gene H3K27ac hESC enhancer GRCh37_chr17:29472253-29472846 Neighboring gene NF1 intron 1 Alu-mediated recombination region Neighboring gene NF1 intron 2 Alu-mediated recombination region Neighboring gene NF1 intron 3 Alu-mediated recombination region Neighboring gene NF1 intron 8 Alu-mediated recombination region Neighboring gene uncharacterized LOC101927057 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12008 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12009 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12010 Neighboring gene ecotropic viral integration site 2B Neighboring gene oligodendrocyte myelin glycoprotein Neighboring gene NF1 intron 50 Alu-mediated recombination region Neighboring gene ecotropic viral integration site 2A Neighboring gene Sharpr-MPRA regulatory region 6872 Neighboring gene adenylate kinase 4 pseudogene 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:29717908-29718497 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:29727239-29727740 Neighboring gene RAB11 family interacting protein 4 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:29738471-29739436 Neighboring gene uncharacterized LOC124903977 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:29741367-29742330 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:29742806-29743646 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:29743647-29744486 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:29751937-29752664 Neighboring gene uncharacterized LOC105371725

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Cafe-au-lait macules with pulmonary stenosis
    MedGen: C0553586 OMIM: 193520 GeneReviews: Not available
    Compare labs
    Juvenile myelomonocytic leukemia
    MedGen: C0349639 OMIM: 607785 GeneReviews: Not available
    Compare labs
    Neurofibromatosis, familial spinal
    MedGen: C1834235 OMIM: 162210 GeneReviews: Not available
    Compare labs
    Neurofibromatosis, type 1 Compare labs
    Neurofibromatosis-Noonan syndrome
    MedGen: C2931482 OMIM: 601321 GeneReviews: Not available
    Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2023-02-12)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2023-02-12)

    ClinGen Genome Curation PagePubMed

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • FLJ21220, DKFZp686J1293

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables GTPase activator activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables phosphatidylcholine binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables phosphatidylethanolamine binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in MAPK cascade ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in Rac protein signal transduction IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in Ras protein signal transduction ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in Schwann cell development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in Schwann cell migration IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in Schwann cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in actin cytoskeleton organization ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in adrenal gland development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in amygdala development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in angiogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in artery morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in brain development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in camera-type eye morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cell communication ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cellular response to heat IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cerebral cortex development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cognition IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in collagen fibril organization ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in endothelial cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in extracellular matrix organization ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in extrinsic apoptotic signaling pathway in absence of ligand IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in extrinsic apoptotic signaling pathway via death domain receptors IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in fibroblast proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in forebrain astrocyte development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in forebrain morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in gamma-aminobutyric acid secretion, neurotransmission IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in glutamate secretion, neurotransmission IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in hair follicle maturation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in heart development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in liver development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in long-term synaptic potentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in mast cell apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in mast cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in metanephros development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in myelination in peripheral nervous system ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in myeloid leukocyte migration IEA
    Inferred from Electronic Annotation
    more info
     
    acts_upstream_of_or_within negative regulation of MAPK cascade IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of MAPK cascade ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of Rac protein signal transduction IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of Ras protein signal transduction IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of Schwann cell migration IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of Schwann cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of angiogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of astrocyte differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    acts_upstream_of_or_within negative regulation of cell migration IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of cell-matrix adhesion IEA
    Inferred from Electronic Annotation
    more info
     
    acts_upstream_of_or_within negative regulation of endothelial cell proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of endothelial cell proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of fibroblast proliferation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of leukocyte migration IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of mast cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of neuroblast proliferation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of neurotransmitter secretion IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of oligodendrocyte differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of osteoclast differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of protein import into nucleus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of stem cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of vascular associated smooth muscle cell migration IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in neural tube development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in neuroblast proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in neuron apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in observational learning IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in oligodendrocyte differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in osteoblast differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in osteoclast differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in peripheral nervous system development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in phosphatidylinositol 3-kinase/protein kinase B signal transduction ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in pigmentation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of GTPase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    acts_upstream_of_or_within positive regulation of GTPase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of apoptotic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of endothelial cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of extrinsic apoptotic signaling pathway in absence of ligand IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of mast cell apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of neuron apoptotic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of vascular associated smooth muscle cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in protein import into nucleus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulation of ERK1 and ERK2 cascade IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulation of angiogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of blood vessel endothelial cell migration IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of bone resorption ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of cell-matrix adhesion ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of gene expression IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulation of glial cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of long-term neuronal synaptic plasticity IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulation of long-term synaptic potentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulation of postsynapse organization IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulation of synaptic transmission, GABAergic IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to hypoxia ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in skeletal muscle tissue development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in smooth muscle tissue development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in spinal cord development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in stem cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in sympathetic nervous system development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in vascular associated smooth muscle cell migration IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in vascular associated smooth muscle cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in visual learning ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in wound healing ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Component Evidence Code Pubs
    located_in axon IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in dendrite IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
     
    located_in membrane HDA PubMed 
    located_in nucleolus IEA
    Inferred from Electronic Annotation
    more info
     
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    located_in nucleus ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
     
    located_in presynapse IEA
    Inferred from Electronic Annotation
    more info
     

    General protein information

    Preferred Names
    neurofibromin
    Names
    neurofibromatosis 1
    neurofibromatosis-related protein NF-1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_009018.1 RefSeqGene

      Range
      4951..287701
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_214

    mRNA and Protein(s)

    1. NM_000267.3NP_000258.1  neurofibromin isoform 2

      See identical proteins and their annotated locations for NP_000258.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame coding exon compared to transcript variant 1, resulting in a shorter isoform (2) missing an internal 21 aa segment, compared to isoform 1.
      Source sequence(s)
      AC135724, AK026658, CN415204, D12625, M82814
      Consensus CDS
      CCDS11264.1
      UniProtKB/TrEMBL
      A0A8I5KWR6
      Related
      ENSP00000348498.3, ENST00000356175.7
      Conserved Domains (4) summary
      cd05130
      Location:11981530
      RasGAP_Neurofibromin; Ras-GTPase Activating Domain of neurofibromin
      smart00323
      Location:11871536
      RasGAP; GTPase-activator protein for Ras-like GTPases
      cd13313
      Location:17071816
      PH_NF1; Neurofibromin-1 Pleckstrin homology-like domain
      pfam13716
      Location:15811707
      CRAL_TRIO_2; Divergent CRAL/TRIO domain
    2. NM_001042492.3NP_001035957.1  neurofibromin isoform 1

      See identical proteins and their annotated locations for NP_001035957.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1), with an additional in-frame coding exon, represents the longest transcript and encodes the longest isoform (1). Studies suggest preferential C->U RNA editing of transcripts containing this exon.
      Source sequence(s)
      AC135724, AK026658, BP271334, BX391799, D12625, M89914
      Consensus CDS
      CCDS42292.1
      UniProtKB/Swiss-Prot
      O00662, P21359, Q14284, Q14930, Q14931, Q9UMK3
      UniProtKB/TrEMBL
      A0A8I5KWR6
      Related
      ENSP00000351015.4, ENST00000358273.9
      Conserved Domains (3) summary
      cd05130
      Location:11981551
      RasGAP_Neurofibromin; Ras-GTPase Activating Domain of neurofibromin
      cd13313
      Location:17281837
      PH_NF1; Neurofibromin-1 Pleckstrin homology-like domain
      pfam13716
      Location:16021736
      CRAL_TRIO_2; Divergent CRAL/TRIO domain
    3. NM_001128147.3NP_001121619.1  neurofibromin isoform 3

      See identical proteins and their annotated locations for NP_001121619.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks multiple 3' exons and has an alternate 3' end, as compared to variant 1. The resulting isoform (3) has a much shorter and different C-terminus, and lacks ras-GTPase activating domain and SEC14 domain, compared to isoform 1.
      Source sequence(s)
      D12625, D42072, M82814
      Consensus CDS
      CCDS45645.1
      UniProtKB/TrEMBL
      A8K1M1
      Related
      ENSP00000412921.4, ENST00000431387.8

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

      Range
      31094927..31377677
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_025791803.1 Reference GRCh38.p14 PATCHES

      Range
      174101..456540
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      32040661..32323039
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)