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General Information
Name
amyotrophic lateral sclerosis 4
FlyBase ID
FBhh0000611
Overview

This report describes amyotrophic lateral sclerosis 4 (ALS4), which is a subtype of amyotrophic lateral sclerosis; ALS4 exhibits autosomal dominant inheritance. The human gene implicated in this disease is Senataxin (SETX), which encodes a probable RNA/DNA helicase involved in diverse aspects of RNA metabolism and DNA repair. There is a single ortholog in Drosophila, CG7504, for which RNAi-targeting constructs and an allele caused by insertional mutagenesis have been generated.

The SETX gene is also implicated in a second disease (spinocerebellar ataxia autosomal recessive 1; FBhh0000612); this Drosophila model makes use of two variants specifically associated with ALS4.

Multiple UAS constructs of the human Hsap\SETX gene have been introduced into flies, including wild-type and variants associated with disease. Variant(s) implicated in human disease tested (as transgenic human gene, SETX): the T3I and R2136H variant forms have been introduced into flies; both of these variants are implicated in ALS4.

The Drosophila CG7504 gene has not been characterized.

[updated Sep. 2017 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: amyotrophic lateral sclerosis
Symptoms and phenotype

Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. ALS usually begins with asymmetric involvement of the muscles in middle adult life. Approximately 10% of ALS cases are familial (Siddique and Deng, 1996, pubmed:8875253). ALS is sometimes referred to as 'Lou Gehrig disease' after the famous American baseball player who was diagnosed with the disorder. [from OMIM:105400, 2015.02.11]

Specific Disease Summary: amyotrophic lateral sclerosis 4
OMIM report

[AMYOTROPHIC LATERAL SCLEROSIS 4, JUVENILE; ALS4](https://omim.org/entry/602433)

Human gene(s) implicated

[SENATAXIN; SETX](https://omim.org/entry/608465)

Symptoms and phenotype

Childhood- and adolescent-onset forms of familial ALS carry the designation 'juvenile ALS.' [from OMIM:602433; 2017.09.12]

Individuals affected with ALS4 usually have an onset of symptoms at age less than 25 years, a slow rate of progression, and a normal life span (Chen et al., 2004; pubmed:15106121). [from OMIM:602433; 2017.09.12]

Genetics

This form of juvenile ALS (ALS4) is caused by mutations in the senataxin gene (SETX). ALS4 exhibits autosomal dominant inheritance. [from OMIM:602433; 2017.09.12]

Cellular phenotype and pathology
Molecular information

Moreira et al. (2004; pubmed:14770181) suggested that senataxin may have both RNA and DNA helicase activities and that senataxin acts in the DNA repair pathway. [from OMIM:608465; 2017.09.12]

SETX (Senataxin) encodes a probable RNA/DNA helicase involved in diverse aspects of RNA metabolism, DNA repair, and genomic integrity. [Gene Cards, SETX; 2017.09.12]

External links
Disease synonyms
ALS4
amyotrophic lateral sclerosis 4, juvenile
neuronopathy, distal hereditary motor, with pyramidal features
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
Symbol / Name
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)
    Cellular component (GO)
    Gene Groups / Pathways
    Comments on ortholog(s)

    Moderate-scoring ortholog of human gene SETX (1 Drosophila to 1 human); Dmel\CG7504 shares 21% identity and 36% 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 (0 groups)
    Alleles Reported to Model Human Disease (Disease Ontology) (4 alleles)
    Models Based on Experimental Evidence ( 4 )
    Modifiers Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Interaction
    References
    Genetic Tools, Stocks and Reagents
    Sources of Stocks
    Contact lab of origin for a reagent not available from a public stock center.
    Bloomington Stock Center Disease Page
    Selected mammalian transgenes
    Allele
    Transgene
    Publicly Available Stocks
    Selected Drosophila transgenes
    Allele
    Transgene
    Publicly Available Stocks
    RNAi constructs available
    Allele
    Transgene
    Publicly Available Stocks
    Selected Drosophila classical alleles
    Allele
    Allele class
    Mutagen
    Publicly Available Stocks
    References (6)