NF2 (neurofibromatosis type 2)

2001-02-01 James F Gusella Affiliation

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

Identity

HGNC

NF2

LOCATION

22q12.2

LOCUSID

4771

ALIAS

ACN,BANF,SCH,merlin-1

FUSION GENES

Show Gene Fusions

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 ID	Last Year	Title	Authors
9425229	1998	Impaired interaction of naturally occurring mutant NF2 protein with actin-based cytoskeleton and membrane.	Deguen B et al
10887156	2000	Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2.	Giovannini M et al
10214350	1999	Merlin: the neurofibromatosis 2 tumor suppressor.	Gusella JF et al
11085592	2000	The parental origin of new mutations in neurofibromatosis 2.	Kluwe L et al
10992163	2000	Advances in neurofibromatosis 2 (NF2): a workshop report.	Lim DJ et al
9171370	1997	The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation.	McClatchey AI et al
7747758	1994	Neurofibromatosis 2 (NF2): clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity.	Parry DM et al
8751853	1996	Germ-line mutations in the neurofibromatosis 2 gene: correlations with disease severity and retinal abnormalities.	Parry DM et al
8379998	1993	Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2.	Rouleau GA et al
8755919	1996	Type of mutation in the neurofibromatosis type 2 gene (NF2) frequently determines severity of disease.	Ruttledge MH et al
8453669	1993	A 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 ID	Transcript ID	Uniprot
ENSG00000186575	ENST00000334961	P35240
ENSG00000186575	ENST00000334961	A0A024R1D9
ENSG00000186575	ENST00000338641	P35240
ENSG00000186575	ENST00000338641	A0A024R1J8
ENSG00000186575	ENST00000353887	P35240
ENSG00000186575	ENST00000353887	A0A024R1D9
ENSG00000186575	ENST00000361166	P35240
ENSG00000186575	ENST00000361452	P35240
ENSG00000186575	ENST00000361452	A0A024R1F6
ENSG00000186575	ENST00000361676	P35240
ENSG00000186575	ENST00000361676	A0A024R1I0
ENSG00000186575	ENST00000397789	P35240
ENSG00000186575	ENST00000397789	A0A024R1J9
ENSG00000186575	ENST00000403435	P35240
ENSG00000186575	ENST00000403999	P35240
ENSG00000186575	ENST00000403999	A0A024R1J9
ENSG00000186575	ENST00000413209	P35240
ENSG00000186575	ENST00000432151	P35240
ENSG00000186575	ENST00000672461	A0A024R1J9
ENSG00000186575	ENST00000672896	A0A024R1J9

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Tight junction	KEGG	ko04530
Tight junction	KEGG	hsa04530
Hippo signaling pathway	KEGG	hsa04390
Hippo signaling pathway	KEGG	ko04390
Hippo signaling	KEGG	hsa_M00683
Hippo signaling	KEGG	M00683
Signal Transduction	REACTOME	R-HSA-162582
Signaling by Rho GTPases	REACTOME	R-HSA-194315
RHO GTPase Effectors	REACTOME	R-HSA-195258
RHO GTPases activate PAKs	REACTOME	R-HSA-5627123
Hippo signaling pathway -multiple species	KEGG	ko04392
Hippo signaling pathway -multiple species	KEGG	hsa04392

Protein levels (Protein atlas)

Not detected

Low

Medium

High

PharmGKB

Entity ID	Name	Type	Evidence	Association	PK	PD	PMIDs
PA446338	Neurofibromatosis 2	Disease	Literature, MultilinkAnnotation	associated			23788249

References

Pubmed ID	Year	Title	Citations
20054297	2010	Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes.	458
20178741	2010	Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus.	138
25706233	2015	A molecular mechanotransduction pathway regulates collective migration of epithelial cells.	98
19451225	2009	NF2/merlin is a novel negative regulator of mTOR complex 1, and activation of mTORC1 is associated with meningioma and schwannoma growth.	96
21481793	2011	A tight junction-associated Merlin-angiomotin complex mediates Merlin's regulation of mitogenic signaling and tumor suppressive functions.	95
25026211	2014	Merlin/NF2 loss-driven tumorigenesis linked to CRL4(DCAF1)-mediated inhibition of the hippo pathway kinases Lats1 and 2 in the nucleus.	88
24848258	2014	Merlin deficiency predicts FAK inhibitor sensitivity: a synthetic lethal relationship.	81
24356468	2013	Inactivation of the Hippo tumour suppressor pathway by integrin-linked kinase.	74
16885985	2006	Tumorigenic transformation by CPI-17 through inhibition of a merlin phosphatase.	71
25488749	2015	Whole-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-(neurofibromatosis-type-2)

Historical Card

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

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 Affiliation

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