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Symbol NF2 contributors: mct/shn - updated : 11-12-2013
HGNC name neurofibromin 2
HGNC id 7773
Corresponding disease
NF2 neurofibromatosis 2
SCWT schwannomatosis
Location 22q12.2      Physical location : 29.999.544 - 30.094.583
Genatlas name schwannomerlin
Synonym name
  • schwannomin
  • merlin
  • moesin-ezrin-radizin-like protein
  • moesin-ezrin-radixin-like protein
  • moesin-ezrin-radixin like
  • schwannomerlin
  • neurofibromin 2 (bilateral acoustic neuroma)
  • neurofibromin-2
  • neurofibromin 2 (merlin)
  • Synonym symbol(s) SCH, ACN, BANF, Merlin
    TYPE functioning gene
    STRUCTURE 95.05 kb     17 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    Map cen - D22S275 - D22S1150 - NF2 NF2 - D22S1176 - D22S273 - qter
    Physical map
    LOC284901 22q12.2 similar to bA436C9.2 (PUTATIVE novel protein similar to part of HSP70/HSP90 organizing protein and transformation sensitive protein) CHEK2 22q12.1 CHK2 checkpoint homolog (S. pombe) HSC20 22q12.2 J-type co-chaperone HSC20 FLJ33814 22q12.2 hypothetical protein FLJ33814 XBP1 22q12.2 X-box binding protein 1 LOC388890 22 LOC388890 FLJ12747 22q12.1 novel C3HC4 type Zinc finger (ring finger) HS747E2A 22q12.1 hypothetical protein HS747E2A KREMEN1 22q12.1 kringle containing transmembrane protein 1 EMU1 22q12.2 emilin and multimerin-domain containing protein 1 C22orf3 22q12.1-q12.2 chromosome 22 open reading frame 3 EWSR1 22q12.2 Ewing sarcoma breakpoint region 1 GAS2L1 22q12.2 growth arrest-specific 2 like 1 RRP22 22q12.2 growth arrest-specific 2 like 1 AP1B1 22q12.2 adaptor-related protein complex 1, beta 1 subunit RFPL1 22q12.2 ret finger protein-like 1 NEFH 22q12.2 neurofilament, heavy polypeptide 200kDa C22orf19 22q12 chromosome 22 open reading frame 19 NIPSNAP1 22q12.2 nipsnap homolog 1 (C. elegans) NF2 22q12.2 neurofibromin 2 (bilateral acoustic neuroma) CABP7 22q12.2 calcium binding protein 7 LOC55954 22cen-q12.3 hypothetical protein LOC55954 HSPC051 22cen-q12.3 ubiquinol-cytochrome c reductase complex (7.2 kD) ASC1p100 22q12.1 ASC-1 complex subunit P100 MTMR3 22q12.2 myotubularin related protein 3 LOC391326 22 similar to h2-calponin MGC26710 22q12.2 hypothetical protein MGC26710 LIF 22q12.2 leukemia inhibitory factor (cholinergic differentiation factor) OSM 22q12.2 oncostatin M TBC1D10 22q12.1-qter TBC1 domain family, member 10 SF3A1 22q12.1 splicing factor 3a, subunit 1, 120kDa LOC388891 22 similar to hypothetical protein 4930562D19 LOC200312 22q12.2 similar to RIKEN cDNA 0610009J22 SEC14L2 22q12.2 SEC14-like 2 (S. cerevisiae) HSPC242 22q hypothetical protein HSPC242 LOC391327 22 similar to solute carrier family 39 (zinc transporter), member 1; zinc-iron regulated transporter-like gene; solute carrier family 39 (zinc transporter), member 3; zinc/iron regulated transporter-like SEC14L3 22q12.2 SEC14-like 3 (S. cerevisiae) LOC376844 SEC14L4 22q12.1 SEC14-like 4 (S. cerevisiae) PTPNS1L 22q12.2 protein tyrosine phosphatase, non-receptor type substrate 1-like CST 22q12.2 protein tyrosine phosphatase, non-receptor type substrate 1-like PES1 22q12.2 pescadillo homolog 1, containing BRCT domain (zebrafish)
    TRANSCRIPTS type messenger
    text several alternatively spliced isoforms
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 - 6046 69.7 595 - 2005 16007223
  • isoform 1
  • 17 splicing 6091 - 590 - 2005 16007223
  • isoform 2
  • 16 splicing 3126 - 590 - 2005 16007223
  • isoform 2
  • 16 splicing 5965 - 548 - 2005 16007223
  • variant de1E2
  • isoform 5
  • 16 splicing 5968 - 549 - 2005 16007223
  • variant de1E3
  • isoform 6
  • 15 splicing 5842 - 507 - 2005 16007223
  • variant de1E2/3
  • isoform 7
  • 15 splicing 2217 - 507 - 2005 16007223
  • isoform 7
  • 17 splicing 6106 - 590 - 2005 16007223
  • isoform 2
  • 5 splicing 4756 - 165 - 2005 16007223
  • isoform 8
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Homo sapiens
    Digestiveintestinelarge intestinecolon lowly Homo sapiens
     intestinesmall intestine  highly Homo sapiens
     liver   lowly Homo sapiens
     stomach   moderately Homo sapiens
    Lymphoid/Immunespleen   moderately Homo sapiens
    Nervousbrain   highly Homo sapiens
    Reproductivefemale systemplacenta  moderately Homo sapiens
     male systemtestis  highly Homo sapiens
    Respiratorylung   highly Homo sapiens
    Urinarykidney   moderately Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatum  moderately Homo sapiens
    cell lineage
    cell lines HEK293, SK-N-AS, NT2/E1, T98G, HepG2, HeLa, K562
    at STAGE
    physiological period fetal
    Text brain
  • a globular N terminus with the FERM (EPB41, ezrin, radixin, moesin) domain, which are spliced out in isoforms Mer150/151/, and abolition of FERM domain-mediated phosphoinositide binding of merlin displaces merlin from the membrane and releases it into the cytosol without altering the folding of merlin
  • two tubulin-binding sites, one residing at the N-terminal FERM-domain and another at the C-terminal domain
  • an alpha helical domain
  • a nuclear localization signal (NLS) and Mer162 interacting with actin-based cytoskeletal structures, through the binding of its isoform 2 to fodrin (SPTBN1)
  • two putative terminal binding sequence PBD1 and PBD2 (to binding with PXN)
  • broad C-terminal region (AA 141-595) is necessary for the interaction with the C-terminal Ras-binding domain (RBD) of RALGDS
    interspecies homolog to Nf2, Mus musculus
    ortholog to Nf2, Rattus norvegicus
    ortholog to NF2, Pan troglodytes
  • ezrin-moesin-radixin-like, radixin-like (ERM) family member
  • CATEGORY tumor suppressor
    SUBCELLULAR LOCALIZATION     plasma membrane
  • nucleocytoplasmic transfer through splicing of exon 2
  • lamellipodia membrane protein
  • basic FUNCTION
  • involved in tumor suppression (see TSG22A)
  • responding and participating in reorganization of membrane-cytoplasmic interactions
  • regulating cell-growth, actin-cytoskeleton-mediated functions such as spreading, motility and attachement
  • involved in the maintenance of normal cytoskeletal organization
  • playing a role in receptor-mediated signaling at the cell surface, and may have implications in the regulation of cytoskeletal reorganization
  • plays a key role in the regulation of the Schwann cell microtubule cytoskeleton
  • indirectly regulates cellular pathways involved in tumorigenesis, including cell to cell adhesion, cytoskeletal architecture, and membrane protein organization
  • can mediate contact-dependent inhibition of proliferation by coordinating the establishment of cell:cell contact with down-regulation of EGFR signaling
  • functions as a tumor and metastasis suppressor by controlling cadherin-mediated cell:cell contact
  • inhibits the activation of Pak1
  • plays a role in governing the hematopoietic stem cell pool by stem cell-autonomous or niche-determined processes
  • potent inhibitor of high-grade human glioma
  • may regulate receptor tyrosine kinase signaling, intracellular mitogenic growth control pathways, or adherens junction organization in non-nervous-system cell types
  • competitively inhibits Src binding to ERBB2 and, prevents ERBB2-mediated Src phosphorylation and downstream mitogenic signaling
  • regulates transmembrane receptors (such as ERB2 and ERB3) accumulation and signaling at the plasma membrane
  • negative regulator of MTOR, which activation is associated with meningioma and Schwannoma growth
  • inhibits mitogenic signaling at or near the plasma membrane
  • suppresses tumorigenesis by translocating to the nucleus to inhibit VPRBP
  • suppresses tumorigenesis by binding to VPRBP and suppressing its E3 ubiquitin ligase activity
  • can control the abundance and signaling of membrane receptors such as EGFR
  • playing a critical role in controlling homeostasis of the liver stem cell niche
  • may function to coordinate physical contacts and growth factor signaling among different cell types in this unique setting of intercellular communication
  • a role for Merlin in impeding breast malignancy
  • changes in the phosphorylation levels of NF2 and MSN lead likely to changes in epithelial organization
  • important and evolutionarily conserved molecular function of NF2 is to promote the membrane association of LATS1/LATS2
  • CELLULAR PROCESS cell life, proliferation/growth
    cell organization/biogenesis
    cell communication
    a component
    small molecule
  • Na(+)-H+ exchanger, NHE-RF
  • betaII-spectrin
  • Ezrin
  • SCHIP-1
  • HGF-regulated tyrosine kinase substrate, HRS
  • syntenin
  • beta-fodrin
  • Paxillin, beta 1 integrin and erbB2
  • p21-activated kinase 1, Pak1
  • transactivation-responsive RNA-binding protein, TRBP
  • magicin
  • merlin-associated protein, MAP
  • Ral guanine nucleotide dissociation stimulator, RALGDS
  • HEI10
  • NF2-associated GTP binding protein, dubbed NGB
  • protein kinase Akt
  • WD40-containing adaptor protein VprBP and E3 ubiquitin ligase complex
  • E3 ubiquitin ligase VPRBP
  • phosphoinositides, including PIK3CA
  • AMOT functions downstream of NF2 and upstream of ARHGAP17, a small GTPase Activating Protein, as a positive regulator of RAC1
  • COP9 Signalosome, CSN
  • disruption of the actin cytoskeleton promotes NF2-LATS1 interactions, which implicates NF2 in actin-mediated regulation of Hippo signaling
  • cell & other
  • adherens junction components
    Phosphorylated by protein kinase Akt
    Other regulation of NF2 nucleocytoplasmic transfer by CRM1-dependent nuclear export signal in exon 15
    downregulation of PPP1R14A induces merlin dephosphorylation, inhibits Ras activation and abolishes the transformed phenotype
    corresponding disease(s) NF2 , SCWT
    related resource Neurofibromatosis Type II
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in ependymomas
    tumoral mosaic      
    in bilateral vestibular schwannomas
    tumoral     --over  
    in endometrial cancer metastasis
    tumoral       loss of function
    in meningioma, acoustic neurinoma
    tumoral   deletion    
    in the developing liver leads to a rapid and dramatic expansion of liver progenitor cells throughout the liver, and subsequently to the development of CC and metastatic hepatocellular carcinoma
    tumoral somatic mutation      
    associated with germinal SMARCB1 mutations in familial multiple meningiomas
    tumoral       loss of function
    of NF2, NIPSNAP1, UGT2B17, and LPIN2 genes during progression of a prostate epithelial cell line to a malignant metastatic state
    Variant & Polymorphism
    Candidate gene
    Therapy target
    ErbB2 inhibitors and Src kinase inhibitors in clinical studies for the treatment of breast cancer and myelogenous leukemia may prove beneficial for the treatment of tumors characterized by merlin loss of function
  • Nf2 hemizygous mice do not develop schwannomas but mainly osteosarcomas
  • conditional homozygous Nf2 knockout mice showed characteristics of neurofibromatosis type 2 including schwannomas, Schwann cell hyperplasia, cataract, and osseous metaplasia
  • Mice with conditional deletion of exon 2 in Schwann cells develop schwannomas
  • Nf2 deficiency in primary cells is an inability to undergo contact-dependent growth arrest and to form stable cadherin-containing cell:cell junctions