NF2 (neurofibromatosis type 2)
2001-02-01 James F Gusella AffiliationMolecular 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
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 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
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA446338 | Neurofibromatosis 2 | Disease | Literature, MultilinkAnnotation | associated | 23788249 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38522513 | 2024 | The tumor suppressor NF2 modulates TEAD4 stability and activity in Hippo signaling via direct interaction. | 0 |
| 38613194 | 2024 | Acquired NF2 mutation confers resistance to TRK inhibition in an ex vivo LMNA::NTRK1-rearranged soft-tissue sarcoma cell model. | 0 |
| 38641672 | 2024 | The histone lysine acetyltransferase KAT2B inhibits cholangiocarcinoma growth: evidence for interaction with SP1 to regulate NF2-YAP signaling. | 0 |
| 38953724 | 2024 | NF2 regulates IP3R-mediated Ca(2+) signal and apoptosis in meningiomas. | 0 |
| 38967126 | 2024 | The molecular biology of NF2/Merlin on tumorigenesis and development. | 0 |
| 38522513 | 2024 | The tumor suppressor NF2 modulates TEAD4 stability and activity in Hippo signaling via direct interaction. | 0 |
| 38613194 | 2024 | Acquired NF2 mutation confers resistance to TRK inhibition in an ex vivo LMNA::NTRK1-rearranged soft-tissue sarcoma cell model. | 0 |
| 38641672 | 2024 | The histone lysine acetyltransferase KAT2B inhibits cholangiocarcinoma growth: evidence for interaction with SP1 to regulate NF2-YAP signaling. | 0 |
| 38953724 | 2024 | NF2 regulates IP3R-mediated Ca(2+) signal and apoptosis in meningiomas. | 0 |
| 38967126 | 2024 | The molecular biology of NF2/Merlin on tumorigenesis and development. | 0 |
| 35705112 | 2023 | The emerging role of NF2 alterations in new and established subtypes of renal cell carcinoma. | 0 |
| 36436149 | 2023 | NF2 mutations are associated with resistance to radiation therapy for grade 2 and grade 3 recurrent meningiomas. | 2 |
| 36806881 | 2023 | Proteasomal pathway inhibition as a potential therapy for NF2-associated meningioma and schwannoma. | 1 |
| 36809290 | 2023 | Merlin tumor suppressor function is regulated by PIP2-mediated dimerization. | 1 |
| 36917021 | 2023 | Comprehensive 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 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
