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General Information
Name
neurofibromatosis, type 2
FlyBase ID
FBhh0000765
Disease Ontology Term
Parent Disease
Overview

This report describes neurofibromatosis, type 2 (NF2); NF2 exhibits autosomal dominant inheritance. The human gene implicated in this disease is Neurofibromin 2, which encodes a protein that plays a role in regulating cell proliferation and cell adhesion; the NF2 protein has been shown to interact with cell-surface proteins, proteins involved in cytoskeletal dynamics, and proteins involved in regulating ion transport. There is a single orthologous gene in Drosophila, Mer, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

Multiple UAS constructs of the human Hsap\NF2 gene has been introduced into flies. Heterologous rescue (functional complementation) has been demonstrated using the more prevalent human NF2 isoform. An isoform that differs at the C terminus fails to rescue. Nonsense mutations are the most common type of variant associated with NF2; a number of missense mutations have also been implicated in the disease. Variant(s) implicated in human disease tested (as transgenic human gene, NF2): the R466*, K413E, and L64P variant forms of the human gene have been introduced into flies.

Animals homozygous for an amorphic mutation of Dmel\Mer do not survive to adult stage. Adults homozygous for hypomorphic alleles exhibit eye and wing phenotypes, allowing screens for and characterization of genetic interactions. Targeted loss-of-function effected by RNAi frequently results in mild overproliferation phenotypes. Many genetic and physical interactions for Dmel\Mer have been described; see below and in the Mer gene report.

[updated Mar. 2018 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: neurofibromatosis, type 2
OMIM report

[NEUROFIBROMATOSIS, TYPE II; NF2](https://omim.org/entry/101000)

Human gene(s) implicated

[NEUROFIBROMIN 2; NF2](https://omim.org/entry/607379)

Symptoms and phenotype

Patients develop nervous system tumors (schwannomas, meningiomas, ependymomas, astrocytomas, and neurofibromas), peripheral neuropathy, ophthalmological lesions (cataracts, epiretinal membranes, and retinal hamartomas), and cutaneous lesions (skin tumours) (Asthagiri, et al., 2009; pubmed:19476995).

Neurofibromatosis 2 (NF2) is characterized by bilateral vestibular schwannomas with associated symptoms of tinnitus, hearing loss, and balance dysfunction. The average age of onset is 18 to 24 years. Almost all affected individuals develop bilateral vestibular schwannomas by age 30 years. [Gene Reviews, Neurofibromatosis 2; 2018.03.14]

The central or type II form of neurofibromatosis (NF2) is an autosomal dominant multiple neoplasia syndrome characterized by tumors of the eighth cranial nerve (usually bilateral), meningiomas of the brain, and schwannomas of the dorsal roots of the spinal cord. [from OMIM:101000; 2018.03.14]

Genetics

Neurofibromatosis type II (NF2) is caused by heterozygous mutation in the gene encoding neurofibromin-2 (NF2), which is also called merlin. [from OMIM:101000; 2018.03.14]

Cellular phenotype and pathology
Molecular information

NF2 encodes a protein similar to proteins that are thought to link cytoskeletal components with proteins in the cell membrane. Neurofibromin 2 protein has been shown to interact with cell-surface proteins, proteins involved in cytoskeletal dynamics and proteins involved in regulating ion transport. NF2 appears to be a regulator of the Hippo/SWH signaling pathway, which plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. [Gene Cards, NF2; 2018.03.19]

NF2 plays a role in regulating cell proliferation and cell adhesion (FBrf0226713 and references cited therein).

External links
Disease synonyms
bilateral acoustic neurofibromatosis
neurofibromatosis type II
NF2
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    Merlin (Mer) encodes a FERM domain containing protein that promotes assembly of a functional Hippo signaling complex at the apical cell cortex. It has also been associated with cell junctions and endocytic compartments. [Date last reviewed: 2019-02-28]
    Molecular function (GO)
    Gene Groups / Pathways
    Comments on ortholog(s)

    High-scoring ortholog of human NF2 (1 Drosophila to 1 human); Dmel\Mer shares 47% identity and 65% similarity with the human gene.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Synthetic Gene(s) Used (0)
    Summary of Physical Interactions (41 groups)
    protein-protein
    Interacting group
    Assay
    References
    anti tag coimmunoprecipitation, anti tag western blot, pull down, western blot
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    pull down, autoradiography, anti tag coimmunoprecipitation, western blot
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    pull down, western blot, anti bait coimmunoprecipitation
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, anti tag western blot
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    far western blotting, tag visualisation
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti bait coimmunoprecipitation, anti tag western blot, anti tag coimmunoprecipitation, western blot
    anti tag coimmunoprecipitation, anti tag western blot
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti bait coimmunoprecipitation, western blot, pull down
    anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, western blot
    anti tag coimmunoprecipitation, anti tag western blot, western blot
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, western blot, anti tag western blot, two hybrid
    anti bait coimmunoprecipitation, anti tag western blot, pull down, western blot
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, anti tag western blot
    pull down, autoradiography
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, peptide massfingerprinting
    anti tag coimmunoprecipitation, anti tag western blot
    Alleles Reported to Model Human Disease (Disease Ontology) (0 alleles)
    Genetic Tools, Stocks and Reagents
    References (9)