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NF2 Gene

protein-coding   GIFtS: 69
GCID: GC22P029999

Neurofibromin 2 (Merlin)

(Previous name: neurofibromin 2 (bilateral acoustic neuroma))
  See NF2-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Neurofibromin 2 (Merlin)1 2     merlin2
Neurofibromin 2 (Bilateral Acoustic Neuroma)1 2     Moesin-Ezrin-Radizin-Like Protein2
Moesin-Ezrin-Radixin Like1 2     neurofibromin-22
schwannomin1 2     schwannomerlin2
Moesin-Ezrin-Radixin-Like Protein2 3     Neurofibromin-23
SCH2 3     Schwannomerlin3
ACN2     Schwannomin3
BANF2     

External Ids:    HGNC: 77731   Entrez Gene: 47712   Ensembl: ENSG000001865757   OMIM: 6073795   UniProtKB: P352403   

Export aliases for NF2 gene to outside databases

Previous GC identifers: GC22P026695 GC22P028324 GC22P012962


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for NF2 Gene:
This gene encodes a protein that is similar to some members of the ERM (ezrin, radixin, moesin) family of proteins
that are thought to link cytoskeletal components with proteins in the cell membrane. This gene product has been
shown to interact with cell-surface proteins, proteins involved in cytoskeletal dynamics and proteins involved in
regulating ion transport. This gene is expressed at high levels during embryonic development; in adults,
significant expression is found in Schwann cells, meningeal cells, lens and nerve. Mutations in this gene are
associated with neurofibromatosis type II which is characterized by nervous system and skin tumors and ocular
abnormalities. Two predominant isoforms and a number of minor isoforms are produced by alternatively spliced
transcripts. (provided by RefSeq, Jul 2008)

GeneCards Summary for NF2 Gene:
NF2 (neurofibromin 2 (merlin)) is a protein-coding gene. Diseases associated with NF2 include neurofibromatosis type 5, and benign meningioma. GO annotations related to this gene include cytoskeletal protein binding. An important paralog of this gene is MSN.

UniProtKB/Swiss-Prot: MERL_HUMAN, P35240
Function: Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a
pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with WWC1 can
synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the
Hippo/SWH (Sav/Wts/Hpo) signaling pathway. May act as a membrane stabilizing protein. May inhibit PI3 kinase by
binding to AGAP2 and impairing its stimulating activity. Suppresses cell proliferation and tumorigenesis by
inhibiting the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex

Gene Wiki entry for NF2 (Merlin) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000022.10  NC_018933.2  NT_011520.13  
Regulatory elements:
   Regulatory transcription factor binding sites in the NF2 gene promoter:
         AP-1   STAT3   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidNF2 promoter sequence
   Search Chromatin IP Primers for NF2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat NF2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 22q12.2   Ensembl cytogenetic band:  22q12.2   HGNC cytogenetic band: 22q12.2

NF2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NF2 gene location

GeneLoc information about chromosome 22         GeneLoc Exon Structure

GeneLoc location for GC22P029999:  view genomic region     (about GC identifiers)

Start:
29,999,545 bp from pter      End:
30,094,589 bp from pter
Size:
95,045 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: MERL_HUMAN, P35240 (See protein sequence)
Recommended Name: Merlin  
Size: 595 amino acids; 69690 Da
Subunit: Interacts with SLC9A3R1, HGS and AGAP2. Interacts with LAYN (By similarity). Interacts with SGSM3.
Interacts (via FERM domain) with MPP1. Interacts with WWC1. Interacts with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3
ubiquitin-protein ligase complex. The unphosphorylated form interacts (via FERM domain) with VPRBP/DCAF1
2 PDB 3D structures from and Proteopedia for NF2:
1H4R (3D)        3U8Z (3D)    
Secondary accessions: O95683 Q8WUJ2 Q969N0 Q969Q3 Q96T30 Q96T31 Q96T32 Q96T33 Q9BTW3 Q9UNG9
Q9UNH3 Q9UNH4
Alternative splicing: 10 isoforms:  P35240-1   P35240-2   P35240-3   P35240-4   P35240-5   P35240-6   P35240-7   P35240-8   
P35240-9   P35240-10   

Explore the universe of human proteins at neXtProt for NF2: NX_P35240

Explore proteomics data for NF2 at MOPED

Post-translational modifications: 

  • Phosphorylation of Ser-518 inhibits nuclear localization by disrupting the intramolecular association of the FERM
    domain with the C-terminal tail1
  • Ubiquitinated by the CUL4A-RBX1-DDB1-DCAF1/VprBP E3 ubiquitin-protein ligase complex for ubiquitination and
    subsequent proteasome-dependent degradation1
  • Ubiquitination2 at Lys269, Lys364, Lys396
  • Modification sites at PhosphoSitePlus

  • See NF2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (9 alternative transcripts): 
    NP_000259.1  NP_057502.2  NP_861546.1  NP_861966.1  NP_861967.1  NP_861968.1  NP_861969.1  NP_861970.1  
    NP_861971.1  

    ENSEMBL proteins: 
     ENSP00000344666   ENSP00000384029   ENSP00000354897   ENSP00000384797   ENSP00000335652  
     ENSP00000340626   ENSP00000395885   ENSP00000354529   ENSP00000355183   ENSP00000380891  
     ENSP00000409921   ENSP00000335160  

    NF2 Human Recombinant Protein Products:

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    OriGene Protein Over-expression Lysate for NF2
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    Novus Biologicals NF2 Protein
    Novus Biologicals NF2 Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for NF2

     
    Search eBioscience for Proteins for NF2 

     
    antibodies-online proteins for NF2 (6 products) 

     
    antibodies-online peptides for NF2

    NF2 Antibody Products:

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    Novus Biologicals NF2 Antibodies
    Abcam antibodies for NF2
    Cloud-Clone Corp. Antibodies for NF2
    ThermoFisher Antibody for NF2
    antibodies-online antibodies for NF2 (133 products) 

    NF2 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for NF2
    Cloud-Clone Corp. CLIAs for NF2
    Search eBioscience for ELISAs for NF2 
    antibodies-online kits for NF2 (11 products) 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    AKAP: A-kinase anchor proteins

    Selected InterPro protein domains (see all 14):
     IPR019748 FERM_central
     IPR019750 Band_41_fam
     IPR000798 Ez/rad/moesin_like
     IPR008954 Moesin_tail
     IPR019747 FERM_CS

    Graphical View of Domain Structure for InterPro Entry P35240

    ProtoNet protein and cluster: P35240

    2 Blocks protein domains:
    IPB000299 Band 4.1 domain
    IPB000798 ERM family signature


    UniProtKB/Swiss-Prot: MERL_HUMAN, P35240
    Similarity: Contains 1 FERM domain


    Find genes that share domains with NF2           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: MERL_HUMAN, P35240
    Function: Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a
    pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with WWC1 can
    synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the
    Hippo/SWH (Sav/Wts/Hpo) signaling pathway. May act as a membrane stabilizing protein. May inhibit PI3 kinase by
    binding to AGAP2 and impairing its stimulating activity. Suppresses cell proliferation and tumorigenesis by
    inhibiting the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex

         Genatlas biochemistry entry for NF2:
    ezrin-moesin-radixin-like,merlin,ezrin,moesin,radixin-like (ERM) family member responding and participating in
    reorganization of membrane-cytoplasmic interactions,with several alternatively spliced isoforms,essential in
    mouse for extraembryonic development immediatly prior to gastrulation,involved in the maintenance of normal
    cytoskeletal organization,involved in tumor suppression (see TSG22A)

         Gene Ontology (GO): 3 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003779actin binding IEA--
    GO:0005515protein binding IPI10669747
    GO:0008092cytoskeletal protein binding ----
         
    Find genes that share ontologies with NF2           About GenesLikeMe


    Phenotypes:
         6 GenomeRNAi human phenotypes for NF2:
     Decreased Tat-dependent transc  Decreased p24 protein expressi  Enable proliferation in B-Raf   Increased gamma-H2AX phosphory 
     Synthetic lethal with Ras  Synthetic lethal with cisplati 

         Selected MGI mutant phenotypes (inferred from 6 alleles(MGI details for Nf2) (see all 18):
     behavior/neurological  craniofacial  embryogenesis  endocrine/exocrine gland  growth/size/body 
     hearing/vestibular/ear  homeostasis/metabolism  immune system  integument  liver/biliary system 
     mortality/aging  nervous system  renal/urinary system  reproductive system  respiratory system 

    Find genes that share phenotypes with NF2           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for NF2: Nf2tm2.1Gth Nf2tm1Tyj

       genOway: Develop your customized and physiologically relevant rodent model for NF2

    miRNA
    Products:
        
    miRTarBase miRNAs that target NF2:
    hsa-mir-193b-3p (MIRT016579), hsa-mir-10a-5p (MIRT047749), hsa-mir-1229-3p (MIRT036332), hsa-let-7a-5p (MIRT001853)

    Block miRNA regulation of human, mouse, rat NF2 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate NF2 (see all 35):
    hsa-miR-328 hsa-miR-3146 hsa-miR-146a hsa-miR-25 hsa-miR-1304 hsa-miR-649 hsa-miR-489 hsa-miR-330-3p
    SwitchGear 3'UTR luciferase reporter plasmidNF2 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat NF2

    Gene Editing
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    Clone
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    OriGene ORF clones in mouse, rat for NF2
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    GenScript: all cDNA clones in your preferred vector (see all 9): NF2 (NM_000268)
    Sino Biological Human cDNA Clone for NF2
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for NF2
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NF2
    Addgene plasmids for NF2 

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NF2


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    MERL_HUMAN, P35240: Isoform 1: Cell projection, filopodium membrane; Peripheral membrane protein; Cytoplasmic
    side. Cell projection, ruffle membrane; Peripheral membrane protein; Cytoplasmic side. Nucleus. Note=In a
    fibroblastic cell line, isoform 1 is found homogeneously distributed over the entire cell, with a particularly
    strong staining in ruffling membranes and filopodia. Colocalizes with MPP1 in non-myelin-forming Schwann cells.
    Binds with VPRBP in the nucleus. The intramolecular association of the FERM domain with the C-terminal tail
    promotes nuclear accumulation. The unphosphorylated form accumulates predominantly in the nucleus while the
    phosphorylated form is largely confined to the non-nuclear fractions
    MERL_HUMAN, P35240: Isoform 7: Cytoplasm, perinuclear region. Cytoplasmic granule. Note=Observed in cytoplasmic
    granules concentrated in a perinuclear location. Isoform 7 is absent from ruffling membranes and filopodia
    MERL_HUMAN, P35240: Isoform 9: Cytoplasm, perinuclear region. Cytoplasmic granule. Note=Observed in cytoplasmic
    granules concentrated in a perinuclear location. Isoform 9 is absent from ruffling membranes and filopodia
    MERL_HUMAN, P35240: Isoform 10: Nucleus. Cell projection, filopodium membrane; Peripheral membrane protein;
    Cytoplasmic side. Cell projection, ruffle membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm,
    perinuclear region. Cytoplasmic granule. Cytoplasm, cytoskeleton. Note=In a fibroblastic cell line, isoform 10 is
    found homogeneously distributed over the entire cell, with a particularly strong staining in ruffling membranes
    and filopodia
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytoskeleton5
    nucleus5
    plasma membrane5
    cytosol4
    endosome4
    mitochondrion3

    Gene Ontology (GO): Selected cellular component terms (see all 16):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001726ruffle ----
    GO:0005634nucleus IDA10401006
    GO:0005730nucleolus IDA9537418
    GO:0005737cytoplasm IDA--
    GO:0005769early endosome IDA10861283

    Find genes that share ontologies with NF2           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for NF2 About    
    See pathways by source

    SuperPathContained pathways About
    1Translation Insulin regulation of translation
    ErbB2/ErbB3 signaling events0.31
    2Neuroscience
    Neuroscience
    3Hippo signaling pathway
    Hippo signaling pathway
    4Glioblastoma Multiforme
    Glioblastoma Multiforme
    5Cytoskeletal Signaling
    Cytoskeletal Signaling


    Find genes that share SuperPaths with NF2           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 Downloadable PowerPoint Slide of GeneGlobe Pathway Central Maps for NF2
        Glioblastoma Multiforme

    2 Cell Signaling Technology (CST) Pathways for NF2
        Neuroscience
    Cytoskeletal Signaling

    1 BioSystems Pathway for NF2
        ErbB2/ErbB3 signaling events



    1 Kegg Pathway  (Kegg details for NF2):
        Hippo signaling pathway

        Pathway & Disease-focused RT2 Profiler PCR Arrays including NF2: 
              Oncogenes & Tumor Suppressor Genes in human mouse rat
              Hedgehog Signaling Pathway in human mouse rat
              Tumor Metastasis in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for NF2

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for NF2 (P352401, 3 ENSP000003446664) via UniProtKB, MINT, STRING, and/or I2D (see all 114)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    SLC9A3R1O147451, 3, ENSP000002626134EBI-1014500,EBI-349787 I2D: score=6 STRING: ENSP00000262613
    MED28Q9H2041, 3, ENSP000002373804EBI-1014472,EBI-514199 I2D: score=3 STRING: ENSP00000237380
    GTPBP4Q9BZE41, 3, ENSP000003540404EBI-1014472,EBI-1056249 I2D: score=1 STRING: ENSP00000354040
    AMOTQ4VCS51, 3, ENSP000003610274EBI-1014472,EBI-2511319 I2D: score=2 STRING: ENSP00000361027
    EZRP153113, ENSP000003389344I2D: score=6 STRING: ENSP00000338934
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 20):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001707mesoderm formation IEA--
    GO:0001953negative regulation of cell-matrix adhesion TAS17210637
    GO:0006469negative regulation of protein kinase activity IEA--
    GO:0007398ectoderm development IEA--
    GO:0008156negative regulation of DNA replication IMP17210637

    Find genes that share ontologies with NF2           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for NF2 (MERL)

    Selected Novoseek inferred chemical compound relationships for NF2 gene (see all 12)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    frovatriptan 72 9 15713228 (2), 15746282 (1), 15840706 (1), 15124101 (1) (see all 8)
    ranolazine 46.6 3 18071302 (1), 18373327 (1), 19371824 (1), 20357382 (1)
    deoxyribonucleic acid 17.1 1 8805149 (1)
    tyrosine 3.2 7 15467451 (1), 11560899 (1), 15378014 (1), 7822301 (1) (see all 6)
    progesterone 0 6 11589430 (1), 15912882 (1), 15779237 (1), 11079777 (1)
    threonine 0 3 8035998 (1), 17174922 (1)
    agar 0 6 15605183 (3), 8089100 (1), 12898284 (1)
    cytochalasin d 0 3 9425229 (1), 15087385 (1)
    paraffin 0 2 9676422 (1)
    serine 0 3 8035998 (1), 17174922 (1)



    Find genes that share compounds with NF2           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for NF2 gene (13 alternative transcripts): 
    NM_000268.3  NM_016418.5  NM_181825.2  NM_181828.2  NM_181829.2  NM_181830.2  NM_181831.2  NM_181832.2  
    NM_181833.2  NM_181826.1  NM_181827.1  NM_181834.1  NM_181835.1  

    Unigene Cluster for NF2:

    Neurofibromin 2 (merlin)
    Hs.187898  [show with all ESTs]
    Unigene Representative Sequence: NM_181832
    12 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000338641(uc003agf.4 uc003agb.4 uc003agc.4 uc003agd.4 uc003agg.4 uc003aga.4 uc003age.4 uc003agh.4 uc003agi.4 uc003agj.4)
    ENST00000403435(uc010gvp.3) ENST00000361452(uc011akq.2) ENST00000403999(uc003afy.4 uc003afz.4)
    ENST00000334961 ENST00000353887 ENST00000432151 ENST00000361166 ENST00000361676
    ENST00000397789 ENST00000413209 ENST00000347330
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    Selected qRT-PCR Assays for microRNAs that regulate NF2 (see all 35):
    hsa-miR-328 hsa-miR-3146 hsa-miR-146a hsa-miR-25 hsa-miR-1304 hsa-miR-649 hsa-miR-489 hsa-miR-330-3p
    SwitchGear 3'UTR luciferase reporter plasmidNF2 3' UTR sequence
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    Addgene plasmids for NF2 
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      QuantiFast Probe-based Assays in human, mouse, rat NF2

    Additional mRNA sequence: 

    AF113694.1 AF122827.1 AF369657.1 AF369658.1 AF369659.1 AF369660.1 AF369661.1 AF369662.1 
    AF369663.1 AF369664.1 AF369665.1 AF369666.1 AF369667.1 AF369668.1 AF369700.1 AF369701.1 
    AF369702.1 AF369703.1 AK092306.1 AK092515.1 AK297116.1 BC003112.1 BC007279.1 BC007336.2 
    BC010060.2 BC020257.1 BC071653.1 BC131810.1 CR456530.1 EF517524.1 L11353.1 L28839.1 
    S73854.1 Z22664.1 

    15 DOTS entries:

    DT.456374  DT.101970117  DT.100816368  DT.92004756  DT.75187896  DT.102842611  DT.95266961  DT.91815870 
    DT.100816363  DT.40105974  DT.100661906  DT.100705720  DT.75101995  DT.100816362  DT.75193819 

    Selected AceView cDNA sequences (see all 243):

    BU174818 BM826151 NM_181826 CA434099 BC003112 AF369701 CR456530 BE740613 
    BU196359 F01364 BG253317 AF369661 BU857816 NM_181827 CB162641 AF369700 
    AW150142 BC007336 NM_016418 NM_000268 BM771310 NM_181831 CB135849 AF369663 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for NF2 (see all 10)    About this scheme

    ExUns: 1a · 1b · 1c · 1d · 1e ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17a · 17b ^ 18 ^ 19a · 19b ·
    SP1:                                            -                                                                                         -     -               
    SP2:                                -           -                                                                                               -               
    SP3:                                -                                                                                                     -     -               
    SP4:                                -           -                                                                                                               
    SP5:                                -           -                                                                                   -     -     -               

    ExUns: 19c
    SP1:      
    SP2:      
    SP3:      
    SP4:      
    SP5:      


    ECgene alternative splicing isoforms for NF2

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    NF2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AGTGGCTGTG
    NF2 Expression
    About this image


    NF2 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 3) fully expand
     
     Brain (Nervous System)    fully expand to see all 2 entries
             Cerebral Cortex
     
     Gut Tube (Gastrointestinal Tract)
             Foregut
     
     Neural Tube (Nervous System)
             Telencephalon
    NF2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    NF2 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.187898

    UniProtKB/Swiss-Prot: MERL_HUMAN, P35240
    Tissue specificity: Widely expressed. Isoform 1 and isoform 3 are predominant. Isoform 4, isoform 5 and isoform 6
    are expressed moderately. Isoform 8 is found at low frequency. Isoform 7, isoform 9 and isoform 10 are not
    expressed in adult tissues, with the exception of adult retina expressing isoform 10. Isoform 9 is faintly
    expressed in fetal brain, heart, lung, skeletal muscle and spleen. Fetal thymus expresses isoforms 1, 7, 9 and 10
    at similar levels

        Pathway & Disease-focused RT2 Profiler PCR Arrays including NF2: 
              Oncogenes & Tumor Suppressor Genes in human mouse rat
              Hedgehog Signaling Pathway in human mouse rat
              Tumor Metastasis in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for NF2 gene from Selected species (see all 16)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Nf21 , 5 neurofibromatosis 21, 5 90.36(n)1
    98.49(a)1
      11 (3.00 cM)5
    180161  NM_010898.41  NP_035028.21 
     47658455 
    chicken
    (Gallus gallus)
    Aves NF21 neurofibromin 2 (bilateral acoustic neuroma) 84.4(n)
    95.12(a)
      395158  NM_204497.2  NP_989828.2 
    lizard
    (Anolis carolinensis)
    Reptilia NF26
    neurofibromin 2 (merlin)
    94(a)
    1 ↔ 1
    GL343417.1(36616-41958)
    African clawed frog
    (Xenopus laevis)
    Amphibia BU910407.12   -- 78.6(n)    BU910407.1 
    zebrafish
    (Danio rerio)
    Actinopterygii nf2a1 neurofibromin 2a (merlin) 76.11(n)
    82.8(a)
      561184  NM_001128707.1  NP_001122179.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Mer1 , 3 axis specification cytoskeletal protein
    binding3
    Merlin1
    46(a)3
    57.8(n)1
    50.43(a)1
      1 18E13
    329791  NM_078689.31  NP_523413.11 


    ENSEMBL Gene Tree for NF2 (if available)
    TreeFam Gene Tree for NF2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section

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    Paralogs for NF2 gene
    MSN2  MYLIP2  FRMD4A2  FRMD4B2  RDX2  EZR2  C1orf1062  
    Selected SIMAP similar genes for NF2 using alignment to 9 protein entries:     MERL_HUMAN (see all proteins) (see all similar genes):
    CHID1    FAM78A    C4orf22    COL24A1    CTSS    EML2
    FAM210A    MYB    PTPLA    THEMIS    ZNF737    c-myb
    WARS    AURA2    DCTN5    ENSA    RUFY1    ZCWPW2

    Find genes that share paralogs with NF2           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
    About This Section

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    Selected SNPs for NF2 (see all 1859)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 22 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0430134
    Neurofibromatosis 2 (NF2)4--see VAR_0430132 G C mis40--------
    VAR_0091234
    Neurofibromatosis 2 (NF2)4--see VAR_0091232 L R mis40--------
    VAR_0430164
    Neurofibromatosis 2 (NF2)4--see VAR_0430162 L H mis40--------
    VAR_0008224
    Neurofibromatosis 2 (NF2)4--see VAR_0008222 L P mis40--------
    VAR_0008134
    Neurofibromatosis 2 (NF2)4--see VAR_0008132 E G mis40--------
    VAR_0008194
    Breast ductal carcinoma4--see VAR_0008192 I F mis40--------
    VAR_0430124
    Neurofibromatosis 2 (NF2)4--see VAR_0430122 L P mis40--------
    VAR_0652274
    Neurofibromatosis 2 (NF2)4--see VAR_0652272 C R mis40--------
    VAR_0430114
    Neurofibromatosis 2 (NF2)4--see VAR_0430112 M V mis40--------
    VAR_0008234
    Melanoma4--see VAR_0008232 K I mis40--------

    HapMap Linkage Disequilibrium report for NF2 (29999545 - 30094589 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 5 variations for NF2:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv191315CNV Insertion16902084
    nsv914965CNV Loss21882294
    nsv834172CNV Loss17160897
    dgv4953n71CNV Loss21882294
    nsv515720CNV Gain+Loss19592680

    Human Gene Mutation Database (HGMD): NF2
    Selected Site Specific Mutation Identification with PCR Assays for NF2 (see all 10):
    Cosmic IdAA Change
    22250p.Q362*
    22240p.Q212*
    22209p.Q410*
    22454p.V219M
    22000p.R262*
    5 Site Specific Cancer Mutation PCR Panels containing NF2:
    Brain Cancers
    Oncogene and Tumor Suppressor Panel 384HT
    Cancer Comprehensive Panel 384HT
    Soft Tissue Tumors
    Tumor Suppressor Panel 384HT
    1 Copy Number PCR Panel containing NF2:
    Oncogenes & Tumor Suppressor Genes 384HC
    SeqTarget long-range PCR primers for resequencing NF2
    DNA2.0 Custom Variant and Variant Library Synthesis for NF2

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

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    OMIM gene information: 607379   
    OMIM disorders: 101000  607174  162091  
    UniProtKB/Swiss-Prot: MERL_HUMAN, P35240
  • Neurofibromatosis 2 (NF2) [MIM:101000]: Genetic disorder characterized by bilateral vestibular
    schwannomas (formerly called acoustic neuromas), schwannomas of other cranial and peripheral nerves, meningiomas,
    and ependymomas. It is inherited in an autosomal dominant fashion with full penetrance. Affected individuals
    generally develop symptoms of eighth-nerve dysfunction in early adulthood, including deafness and balance
    disorder. Although the tumors of NF2 are histologically benign, their anatomic location makes management
    difficult, and patients suffer great morbidity and mortality. Note=The disease is caused by mutations affecting
    the gene represented in this entry
  • Schwannomatosis (SCHWA) [MIM:162091]: Schwannomas are benign tumors of the peripheral nerve sheath that
    usually occur singly in otherwise normal individuals. Multiple schwannomas in the same individual suggest an
    underlying tumor-predisposition syndrome. The most common such syndrome is NF2. The hallmark of NF2 is the
    development of bilateral vestibular-nerve schwannomas; but two-thirds or more of all NF2-affected individuals
    develop schwannomas in other locations, and dermal schwannomas may precede vestibular tumors in NF2-affected
    children. There have been several reports of individuals with multiple schwannomas who do not show evidence of
    vestibular schwannoma. Clinical report suggests that schwannomatosis is a clinical entity distinct from other
    forms of neurofibromatosis. Note=The disease is caused by mutations affecting the gene represented in this entry
  • Mesothelioma, malignant (MESOM) [MIM:156240]: An aggressive neoplasm of the serosal lining of the chest.
    It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other
    regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos. Note=The
    disease may be caused by mutations affecting the gene represented in this entry

  • Selected diseases for NF2 (see all 35):    
    About MalaCards
    neurofibromatosis type 5    benign meningioma    anaplastic ependymoma    neurilemmomatosis
    cellular schwannoma    tanycytic ependymoma    pediatric meningioma    plexiform schwannoma
    neuroma    spinal cord ependymoma    chronic angina    acoustic neuroma
    transitional meningioma    meningioma, nf2-related, somatic    facial paralysis    sclerosing perineurioma
    fibrous meningioma    neurofibrosarcoma    plexiform neurofibroma    pten hamartoma tumor syndrome

    9 diseases from the University of Copenhagen DISEASES database for NF2:
    Neurofibromatosis     Neurilemmoma     Meningioma     Neurofibroma
    Malignant mesothelioma     Spinal meningioma     Facial paralysis     Tanycytic ependymoma
    Benign mesothelioma

    Find genes that share disorders with NF2           About GenesLikeMe

    Selected Novoseek inferred disease relationships for NF2 gene (see all 73)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    neurofibromatosis type 2 97.8 188 8666669 (2), 9013725 (2), 15000491 (2), 20054405 (2) (see all 99)
    schwannoma 89.9 215 9752976 (8), 7529050 (5), 9403715 (5), 11773000 (5) (see all 85)
    meningioma 87.7 258 17319281 (8), 16612978 (6), 10606247 (5), 9055299 (5) (see all 86)
    neurofibromatosis 83.8 31 1293176 (2), 12191989 (2), 11388764 (1), 11391665 (1) (see all 24)
    schwannomatosis 82.3 18 18285426 (4), 16078050 (2), 12975302 (2), 9399891 (1)
    neuroma acoustic 81.1 48 17007372 (6), 19142715 (3), 19141242 (3), 9752976 (2) (see all 18)
    nervous system tumor 78.4 7 10790209 (1), 8909442 (1), 15797715 (1), 10720287 (1) (see all 5)
    neurofibromatosis type 1 72.6 18 9190537 (1), 10358844 (1), 11391665 (1), 15000491 (1) (see all 16)
    ependymoma 71.9 33 12011257 (5), 10433955 (5), 17509660 (4), 9100669 (4) (see all 10)
    ependymal tumors 69.3 1 10433955 (1)

    Genatlas disease: NF2
    neurofibromatosis 2,autosomal dominant disorder characterized by tumors of neural-crest origin cells,with
    biallelic inactivation in schwannomas,meningiomas,mesotheliomas,and testicular anomalies such as presenile lens
    opacities and retinal hamartomas,(merlin/Schwannomin defect)

    GeneTests: NF2
    GeneReviews: NF2
    Genetic Association Database (GAD): NF2
    Human Genome Epidemiology (HuGE) Navigator: NF2 (11 documents)
    Tumor Gene Database (TGDB): NF2

    Export disorders for NF2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

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    PubMed articles for NF2 gene, integrated from 10 sources (see all 541):
    (articles sorted by number of sources associating them with NF2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation. (PubMed id 18332868)1, 2, 9 Huang J. and Chen J. (Oncogene 2008)
    2. Mutations of the neurofibromatosis type 2 gene and lack of the gene product in vestibular schwannomas. (PubMed id 7951231)1, 2, 9 Sainz J.... Pulst S.M. (Hum. Mol. Genet. 1994)
    3. The structure of the FERM domain of merlin, the neurofibromatosis type 2 gene product. (PubMed id 11856822)1, 2, 9 Kang B.S.... Derewenda Z.S. (Acta Crystallogr. D 2002)
    4. Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus. (PubMed id 20178741)1, 2, 9 Li W.... Giancotti F.G. (Cell 2010)
    5. Genotyping of patients with sporadic and radiation-associated meningiomas. (PubMed id 15824172)1, 4, 9 Sadetzki S....Friedman E. (amp 2005)
    6. Neurofibromatosis 2 (NF2) tumor suppressor merlin inhibits phosphatidylinositol 3-kinase through binding to PIKE-L. (PubMed id 15598747)1, 2, 9 Rong R.... Ye K. (Proc. Natl. Acad. Sci. U.S.A. 2004)
    7. Germ-line NF2 mutations and disease severity in neurofibromatosis type 2 patients with retinal abnormalities. (PubMed id 10090912)1, 2, 9 Baser M.E.... Mautner V.-F. (Am. J. Hum. Genet. 1999)
    8. NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common interactor for merlin and ERM (MERM) proteins. (PubMed id 9430655)1, 2, 9 Murthy A.... Ramesh V. (J. Biol. Chem. 1998)
    9. A missense mutation in the NF2 gene results in moderate and mild clinical phenotypes of neurofibromatosis type 2. (PubMed id 8566958)1, 2, 9 Kluwe L. and Mautner V.-F. (Hum. Genet. 1996)
    10. Mutations in transcript isoforms of the neurofibromatosis 2 gene in multiple human tumour types. (PubMed id 8162073)1, 2, 9 Bianchi A.B.... Kley N. (Nat. Genet. 1994)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 4771 HGNC: 7773 AceView: NF2 Ensembl:ENSG00000186575 euGenes: HUgn4771
    ECgene: NF2 Kegg: 4771 H-InvDB: NF2

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for NF2 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for NF2 Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=NF2[genesymbol]

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for NF2 gene:
    Search GeneIP for patents involving NF2

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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