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
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
Entity name
sporadic schwannoma
Entity name
other tumours: ependymoma; mesothelioma

Article 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
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

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
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA446338Neurofibromatosis 2DiseaseLiterature, MultilinkAnnotationassociated23788249

References

Pubmed IDYearTitleCitations
385225132024The tumor suppressor NF2 modulates TEAD4 stability and activity in Hippo signaling via direct interaction.0
386131942024Acquired NF2 mutation confers resistance to TRK inhibition in an ex vivo LMNA::NTRK1-rearranged soft-tissue sarcoma cell model.0
386416722024The histone lysine acetyltransferase KAT2B inhibits cholangiocarcinoma growth: evidence for interaction with SP1 to regulate NF2-YAP signaling.0
389537242024NF2 regulates IP3R-mediated Ca(2+) signal and apoptosis in meningiomas.0
389671262024The molecular biology of NF2/Merlin on tumorigenesis and development.0
385225132024The tumor suppressor NF2 modulates TEAD4 stability and activity in Hippo signaling via direct interaction.0
386131942024Acquired NF2 mutation confers resistance to TRK inhibition in an ex vivo LMNA::NTRK1-rearranged soft-tissue sarcoma cell model.0
386416722024The histone lysine acetyltransferase KAT2B inhibits cholangiocarcinoma growth: evidence for interaction with SP1 to regulate NF2-YAP signaling.0
389537242024NF2 regulates IP3R-mediated Ca(2+) signal and apoptosis in meningiomas.0
389671262024The molecular biology of NF2/Merlin on tumorigenesis and development.0
357051122023The emerging role of NF2 alterations in new and established subtypes of renal cell carcinoma.0
364361492023NF2 mutations are associated with resistance to radiation therapy for grade 2 and grade 3 recurrent meningiomas.2
368068812023Proteasomal pathway inhibition as a potential therapy for NF2-associated meningioma and schwannoma.1
368092902023Merlin tumor suppressor function is regulated by PIP2-mediated dimerization.1
369170212023Comprehensive Genomic Profiling of NF2-Mutated Kidney Tumors Reveals Potential Targets for Therapy.3

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 

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