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FB2026_01
,
released March 12, 2026
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, Setx, 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 Setx gene has not been characterized.
[updated Sep. 2017 by FlyBase; FBrf0222196]
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 MIM:105400, 2015.02.11]
[AMYOTROPHIC LATERAL SCLEROSIS 4, JUVENILE; ALS4](https://omim.org/entry/602433)
[SENATAXIN; SETX](https://omim.org/entry/608465)
Childhood- and adolescent-onset forms of familial ALS carry the designation 'juvenile ALS.' [from MIM: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 MIM:602433; 2017.09.12]
This form of juvenile ALS (ALS4) is caused by mutations in the senataxin gene (SETX). ALS4 exhibits autosomal dominant inheritance. [from MIM:602433; 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]
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 MIM:608465; 2017.09.12]
One to one: 1 human to 1 Drosophila.
Moderate-scoring ortholog of human gene SETX (1 Drosophila to 1 human); Dmel\Setx shares 21% identity and 36% similarity with the human gene.