| Identity |
| Other names | SCH |
| HGNC (Hugo) | NF2 |
| Location | 22q12.1-12.2 |
| Location_base_pair | Starts at 28329545 and ends at 28424589 bp from pter ( according to hg18-Mar_2006) [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 |
| External links |
| 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 articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 09-1997 | Jean-Loup Huret |
| Updated | 03-1998 | Jean-Loup Huret |
| Updated | 02-2001 | James F Gusella |
| Citation |
| This paper should be referenced as such : |
| Huret JL . NF2 (neurofibromatosis type 2). Atlas Genet Cytogenet Oncol Haematol. September 1997 . URL : http://AtlasGeneticsOncology.org/Genes/NF2117.html |
| Huret JL . NF2 (neurofibromatosis type 2). Atlas Genet Cytogenet Oncol Haematol. March 1998 . URL : http://AtlasGeneticsOncology.org/Genes/NF2117.html |
| Gusella JF . NF2 (neurofibromatosis type 2). Atlas Genet Cytogenet Oncol Haematol. February 2001 . URL : http://AtlasGeneticsOncology.org/Genes/NF2117.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Sat Feb 6 13:44:41 CET 2010 |
For comments and suggestions or contributions, please contact us