Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

NF2 (neurofibromatosis type 2)

Identity

Other namesSCH
HGNC (Hugo) NF2
LocusID (NCBI) 4771
Location 22q12.2
Location_base_pair Starts at 29999545 and ends at 30094589 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order 22q12.1-12.2 junction, incidentally not far from EWS

DNA/RNA

Description exons 17 exons (1-15, 17 constitutive, 16 alternatively spliced); spans 120 kb; open reading frame: 1.8 kb
Transcription alternate splicing, in particular after exon 15

Protein

Description called merlin, schwannomin, or SCH; isoform 1 595 amino acids, isoform 2 590 amino acids (due to inclusion of exon 16 in transcript) ; 66 KDa; NH2 -- FERM domain -- large a helix domain -- COOH
Expression wide: in lung, kidney, ovary, breast, placenta, neuroblasts; high in fetal brain
Localisation membrane associated interacts with integral membrane proteins and actin-cytoskeleton
Function membrane-cytoskeleton anchor (as APC also appears to be); role in the development of extraembryonic structures before gastrulation; has characteristics of a tumour suppressor, as has been found in sporadic as well as neurofibromatosis type 2 induced schwannomas and meningiomas
Homology ezrin, radixin, moesin, members of the erythrocytes band 4.1 family, especially in the N-terminal FERM domain

Mutations

Germinal inborn condition of neurofibromatosis type 2 patients: protein truncations due to various frameshift deletions or insertions or nonsense mutations; splice-site or missense mutations are also found; phenotype-genotype correlations are observed (i.e. that severe phenotype are found in cases with protein truncations rather than those with amino acid substitution)
Somatic mutation and allele loss events in tumours in neurofibromatosis type 2 and in sporadic schwannomas and meningiomas are in accordance with the two-hit model for neoplasia, as is found in retinoblastoma

Implicated in

Entity neurofibromatosis type 2
Disease autosomal dominant tumor prone disease; neurofibromatosis type 2 (NF2: the same symbol is used for the disease neurofibromatosis type 2 and the gene) is an hamartoneoplastic syndrome
Prognosis hamartomas have a potential towards neoplasia; those, in NF2, are The tumors of NF2 are slow-growing benign schwannomas which do not progress to malignancy and meningiomas
  
Entity sporadic meningioma
  
Entity sporadic schwannoma
  
Entity other tumours: ependymoma; mesothelioma
  

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors ProstateOverviewID5041 ProstateOverviewID5041 ProstateOverviewID5041

External links

Nomenclature
HGNC (Hugo)NF2   7773
Cards
AtlasNF2117
Entrez_Gene (NCBI)NF2  4771  neurofibromin 2 (merlin)
GeneCards (Weizmann)NF2
Ensembl (Hinxton)ENSG00000186575 [Gene_View]  chr22:29999545-30094589 [Contig_View]  NF2 [Vega]
ICGC DataPortalENSG00000186575
cBioPortalNF2
AceView (NCBI)NF2
Genatlas (Paris)NF2
WikiGenes4771
SOURCE (Princeton)NM_000268 NM_016418 NM_181825 NM_181826 NM_181827 NM_181828 NM_181829 NM_181830 NM_181831 NM_181832 NM_181833 NM_181834 NM_181835
Genomic and cartography
GoldenPath (UCSC)NF2  -  22q12.2   chr22:29999545-30094589 +  22q12.2   [Description]    (hg19-Feb_2009)
EnsemblNF2 - 22q12.2 [CytoView]
Mapping of homologs : NCBINF2 [Mapview]
OMIM101000   162091   607174   607379   
Gene and transcription
Genbank (Entrez)AF113694 AF122827 AF122828 AF123570 AF369657
RefSeq transcript (Entrez)NM_000268 NM_016418 NM_181825 NM_181826 NM_181827 NM_181828 NM_181829 NM_181830 NM_181831 NM_181832 NM_181833 NM_181834 NM_181835
RefSeq genomic (Entrez)AC_000154 NC_000022 NC_018933 NG_009057 NT_011520 NW_001838745 NW_004929430
Consensus coding sequences : CCDS (NCBI)NF2
Cluster EST : UnigeneHs.187898 [ NCBI ]
CGAP (NCI)Hs.187898
Alternative Splicing : Fast-db (Paris)GSHG0019936
Alternative Splicing GalleryENSG00000186575
Gene ExpressionNF2 [ NCBI-GEO ]     NF2 [ SEEK ]   NF2 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP35240 (Uniprot)
NextProtP35240  [Medical]
With graphics : InterProP35240
Splice isoforms : SwissVarP35240 (Swissvar)
Domaine pattern : Prosite (Expaxy)FERM_1 (PS00660)    FERM_2 (PS00661)    FERM_3 (PS50057)   
Domains : Interpro (EBI)Band_41_domain [organisation]   Band_41_fam [organisation]   ERM [organisation]   ERM_C_dom [organisation]   Ez/rad/moesin_like [organisation]   FERM/acyl-CoA-bd_prot_3-hlx [organisation]   FERM_central [organisation]   FERM_CS [organisation]   FERM_domain [organisation]   FERM_N [organisation]   FERM_PH-like_C [organisation]   Moesin_tail [organisation]   PH_like_dom [organisation]   Ubiquitin-rel_dom [organisation]  
Related proteins : CluSTrP35240
Domain families : Pfam (Sanger)ERM (PF00769)    FERM_C (PF09380)    FERM_M (PF00373)    FERM_N (PF09379)   
Domain families : Pfam (NCBI)pfam00769    pfam09380    pfam00373    pfam09379   
Domain families : Smart (EMBL)B41 (SM00295)  
DMDM Disease mutations4771
Blocks (Seattle)P35240
PDB (SRS)1H4R    3U8Z   
PDB (PDBSum)1H4R    3U8Z   
PDB (IMB)1H4R    3U8Z   
PDB (RSDB)1H4R    3U8Z   
Human Protein AtlasENSG00000186575 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP35240
HPRD06980
IPIIPI00414431   IPI00216128   IPI00220308   IPI00304755   IPI00220310   IPI00220311   IPI00220312   IPI00414202   IPI00220314   IPI00220315   IPI00922689   IPI00816094   IPI00220328   IPI00816257   
Protein Interaction databases
DIP (DOE-UCLA)P35240
IntAct (EBI)P35240
FunCoupENSG00000186575
BioGRIDNF2
InParanoidP35240
Interologous Interaction database P35240
IntegromeDBNF2
STRING (EMBL)NF2
Ontologies - Pathways
Ontology : AmiGOmesoderm formation  negative regulation of cell-matrix adhesion  actin binding  protein binding  nucleus  nucleolus  cytoplasm  early endosome  cytoskeleton  plasma membrane  adherens junction  negative regulation of protein kinase activity  ectoderm development  negative regulation of DNA replication  negative regulation of cell proliferation  negative regulation of cell proliferation  Schwann cell proliferation  membrane  extrinsic component of membrane  negative regulation of cell-cell adhesion  lamellipodium  actin cytoskeleton organization  negative regulation of cell migration  cortical actin cytoskeleton  filopodium membrane  cleavage furrow  ruffle membrane  regulation of hippo signaling  odontogenesis of dentin-containing tooth  negative regulation of tyrosine phosphorylation of Stat3 protein  negative regulation of tyrosine phosphorylation of Stat5 protein  negative regulation of MAPK cascade  cell-cell junction organization  negative regulation of JAK-STAT cascade  perinuclear region of cytoplasm  positive regulation of stress fiber assembly  lens fiber cell differentiation  
Ontology : EGO-EBImesoderm formation  negative regulation of cell-matrix adhesion  actin binding  protein binding  nucleus  nucleolus  cytoplasm  early endosome  cytoskeleton  plasma membrane  adherens junction  negative regulation of protein kinase activity  ectoderm development  negative regulation of DNA replication  negative regulation of cell proliferation  negative regulation of cell proliferation  Schwann cell proliferation  membrane  extrinsic component of membrane  negative regulation of cell-cell adhesion  lamellipodium  actin cytoskeleton organization  negative regulation of cell migration  cortical actin cytoskeleton  filopodium membrane  cleavage furrow  ruffle membrane  regulation of hippo signaling  odontogenesis of dentin-containing tooth  negative regulation of tyrosine phosphorylation of Stat3 protein  negative regulation of tyrosine phosphorylation of Stat5 protein  negative regulation of MAPK cascade  cell-cell junction organization  negative regulation of JAK-STAT cascade  perinuclear region of cytoplasm  positive regulation of stress fiber assembly  lens fiber cell differentiation  
Pathways : KEGGHippo signaling pathway   
Protein Interaction DatabaseNF2
Wikipedia pathwaysNF2
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)NF2
snp3D : Map Gene to Disease4771
SNP (GeneSNP Utah)NF2
SNP : HGBaseNF2
Genetic variants : HAPMAPNF2
Exome VariantNF2
1000_GenomesNF2 
ICGC programENSG00000186575 
Cancer Gene: CensusNF2 
Somatic Mutations in Cancer : COSMICNF2 
CONAN: Copy Number AnalysisNF2 
Mutations and Diseases : HGMDNF2
Genomic VariantsNF2  NF2 [DGVbeta]
dbVarNF2
ClinVarNF2
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM101000    162091    607174    607379   
MedgenNF2
GENETestsNF2
Disease Genetic AssociationNF2
Huge Navigator NF2 [HugePedia]  NF2 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneNF2
Homology/Alignments : Family Browser (UCSC)NF2
Phylogenetic Trees/Animal Genes : TreeFamNF2
Chemical/Protein Interactions : CTD4771
Chemical/Pharm GKB GenePA31580
Drug Sensitivity NF2
Clinical trialNF2
Cancer Resource (Charite)ENSG00000186575
Other databases
Probes
Litterature
PubMed214 Pubmed reference(s) in Entrez
CoreMineNF2
iHOPNF2
OncoSearchNF2

Bibliography

A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor.
Trofatter JA, MacCollin MM, Rutter JL, Murrell JR, Duyao MP, Parry DM, Eldridge R, Kley N, Menon AG, Pulaski K
Cell. 1993 ; 72 (5) : 791-800.
PMID 8453669
 
Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2.
Rouleau GA, Merel P, Lutchman M, Sanson M, Zucman J, Marineau C, Hoang-Xuan K, Demczuk S, Desmaze C, Plougastel B
Nature. 1993 ; 363 (6429) : 515-521.
PMID 8379998
 
Neurofibromatosis 2 (NF2): clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity.
Parry DM, Eldridge R, Kaiser-Kupfer MI, Bouzas EA, Pikus A, Patronas N
American journal of medical genetics. 1994 ; 52 (4) : 450-461.
PMID 7747758
 
Germ-line mutations in the neurofibromatosis 2 gene: correlations with disease severity and retinal abnormalities.
Parry DM, MacCollin MM, Kaiser-Kupfer MI, Pulaski K, Nicholson HS, Bolesta M, Eldridge R, Gusella JF
American journal of human genetics. 1996 ; 59 (3) : 529-539.
PMID 8751853
 
Type of mutation in the neurofibromatosis type 2 gene (NF2) frequently determines severity of disease.
Ruttledge MH, Andermann AA, Phelan CM, Claudio JO, Han FY, Chretien N, Rangaratnam S, MacCollin M, Short P, Parry D, Michels V, Riccardi VM, Weksberg R, Kitamura K, Bradburn JM, Hall BD, Propping P, Rouleau GA
American journal of human genetics. 1996 ; 59 (2) : 331-342.
PMID 8755919
 
The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation.
McClatchey AI, Saotome I, Ramesh V, Gusella JF, Jacks T
Genes & development. 1997 ; 11 (10) : 1253-1265.
PMID 9171370
 
Impaired interaction of naturally occurring mutant NF2 protein with actin-based cytoskeleton and membrane.
Deguen B, Mˆ©rel P, Goutebroze L, Giovannini M, Reggio H, Arpin M, Thomas G
Human molecular genetics. 1998 ; 7 (2) : 217-226.
PMID 9425229
 
Merlin: the neurofibromatosis 2 tumor suppressor.
Gusella JF, Ramesh V, MacCollin M, Jacoby LB
Biochimica et biophysica acta. 1999 ; 1423 (2) : M29-M36.
PMID 10214350
 
Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2.
Giovannini M, Robanus-Maandag E, van der Valk M, Niwa-Kawakita M, Abramowski V, Goutebroze L, Woodruff JM, Berns A, Thomas G
Genes & development. 2000 ; 14 (13) : 1617-1630.
PMID 10887156
 
The parental origin of new mutations in neurofibromatosis 2.
Kluwe L, Mautner V, Parry DM, Jacoby LB, Baser M, Gusella J, Davis K, Stavrou D, MacCollin M
Neurogenetics. 2000 ; 3 (1) : 17-24.
PMID 11085592
 
Advances in neurofibromatosis 2 (NF2): a workshop report.
Lim DJ, Rubenstein AE, Evans DG, Jacks T, Seizinger BG, Baser ME, Beebe D, Brackmann DE, Chiocca EA, Fehon RG, Giovannini M, Glazer R, Gusella JF, Gutmann DH, Korf B, Lieberman F, Martuza R, McClatchey AI, Parry DM, Pulst SM, Ramesh V, Ramsey WJ, Ratner N, Rutkowski JL, Ruttledge M, Weinstein DE
Journal of neurogenetics. 2000 ; 14 (2) : 63-106.
PMID 10992163
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written09-1997Jean-Loup Huret
Updated03-1998Jean-Loup Huret
Updated02-2001James F Gusella

Citation

This paper should be referenced as such :
Gusella, JF
NF2 (neurofibromatosis type 2)
Atlas Genet Cytogenet Oncol Haematol. 2001;5(2):91-92.
Free online version   Free pdf version   [Bibliographic record ]
History of this paper:
Gusella, JF. NF2 (neurofibromatosis type 2). Atlas Genet Cytogenet Oncol Haematol. 2001;5(2):91-92.
http://documents.irevues.inist.fr/bitstream/2042/37720/1/02-2001-NF2117.pdf
Atlas Genet Cytogenet Oncol Haematol. March 1998
URL : http://AtlasGeneticsOncology.org/Genes/NF2117.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Jul 26 15:23:13 CEST 2014

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.