NF2 (neurofibromatosis type 2)

2001-02-01   James F Gusella 

Molecular Neurogenetics Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA

Identity

HGNC
LOCATION
22q12.2
LOCUSID
ALIAS
ACN,BANF,SCH,merlin-1
FUSION GENES

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

Proteins

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 name
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 name
sporadic meningioma

Bibliography

Pubmed IDLast YearTitleAuthors
94252291998Impaired interaction of naturally occurring mutant NF2 protein with actin-based cytoskeleton and membrane.Deguen B et al
108871562000Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2.Giovannini M et al
102143501999Merlin: the neurofibromatosis 2 tumor suppressor.Gusella JF et al
110855922000The parental origin of new mutations in neurofibromatosis 2.Kluwe L et al
109921632000Advances in neurofibromatosis 2 (NF2): a workshop report.Lim DJ et al
91713701997The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation.McClatchey AI et al
77477581994Neurofibromatosis 2 (NF2): clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity.Parry DM et al
87518531996Germ-line mutations in the neurofibromatosis 2 gene: correlations with disease severity and retinal abnormalities.Parry DM et al
83799981993Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2.Rouleau GA et al
87559191996Type of mutation in the neurofibromatosis type 2 gene (NF2) frequently determines severity of disease.Ruttledge MH et al
84536691993A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor.Trofatter JA et al

Other Information

Locus ID:

NCBI: 4771
MIM: 607379
HGNC: 7773
Ensembl: ENSG00000186575

Variants:

dbSNP: 4771
ClinVar: 4771
TCGA: ENSG00000186575
COSMIC: NF2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000186575ENST00000334961P35240
ENSG00000186575ENST00000334961A0A024R1D9
ENSG00000186575ENST00000338641P35240
ENSG00000186575ENST00000338641A0A024R1J8
ENSG00000186575ENST00000353887P35240
ENSG00000186575ENST00000353887A0A024R1D9
ENSG00000186575ENST00000361166P35240
ENSG00000186575ENST00000361452P35240
ENSG00000186575ENST00000361452A0A024R1F6
ENSG00000186575ENST00000361676P35240
ENSG00000186575ENST00000361676A0A024R1I0
ENSG00000186575ENST00000397789P35240
ENSG00000186575ENST00000397789A0A024R1J9
ENSG00000186575ENST00000403435P35240
ENSG00000186575ENST00000403999P35240
ENSG00000186575ENST00000403999A0A024R1J9
ENSG00000186575ENST00000413209P35240
ENSG00000186575ENST00000432151P35240
ENSG00000186575ENST00000672461A0A024R1J9
ENSG00000186575ENST00000672896A0A024R1J9

Expression (GTEx)

0
5
10
15
20
25
30
35

Pathways

PathwaySourceExternal ID
Tight junctionKEGGko04530
Tight junctionKEGGhsa04530
Hippo signaling pathwayKEGGhsa04390
Hippo signaling pathwayKEGGko04390
Hippo signalingKEGGhsa_M00683
Hippo signalingKEGGM00683
Signal TransductionREACTOMER-HSA-162582
Signaling by Rho GTPasesREACTOMER-HSA-194315
RHO GTPase EffectorsREACTOMER-HSA-195258
RHO GTPases activate PAKsREACTOMER-HSA-5627123
Hippo signaling pathway -multiple speciesKEGGko04392
Hippo signaling pathway -multiple speciesKEGGhsa04392

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA446338Neurofibromatosis 2DiseaseLiterature, MultilinkAnnotationassociated23788249

References

Pubmed IDYearTitleCitations
200542972010Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes.458
201787412010Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus.138
257062332015A molecular mechanotransduction pathway regulates collective migration of epithelial cells.98
194512252009NF2/merlin is a novel negative regulator of mTOR complex 1, and activation of mTORC1 is associated with meningioma and schwannoma growth.96
214817932011A tight junction-associated Merlin-angiomotin complex mediates Merlin's regulation of mitogenic signaling and tumor suppressive functions.95
250262112014Merlin/NF2 loss-driven tumorigenesis linked to CRL4(DCAF1)-mediated inhibition of the hippo pathway kinases Lats1 and 2 in the nucleus.88
248482582014Merlin deficiency predicts FAK inhibitor sensitivity: a synthetic lethal relationship.81
243564682013Inactivation of the Hippo tumour suppressor pathway by integrin-linked kinase.74
168859852006Tumorigenic transformation by CPI-17 through inhibition of a merlin phosphatase.71
254887492015Whole-exome sequencing reveals frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1 in malignant pleural mesothelioma.66

Citation

James F Gusella

NF2 (neurofibromatosis type 2)

Atlas Genet Cytogenet Oncol Haematol. 2001-02-01

Online version: http://atlasgeneticsoncology.org/gene/117/nf2

Historical Card

1998-03-01 NF2 (neurofibromatosis type 2) by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

1997-09-01 NF2 (neurofibromatosis type 2) by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France