- Tools
- Downloads
- Links
- Community
- About
- Help
FB2026_01
,
released March 12, 2026
This report describes spinocerebellar ataxia 5 (SCA5), which is a subtype of spinocerebellar ataxia; SCA5 is inherited as an autosomal dominant. The human gene implicated in this disease is SPTBN2, which encodes non-erythrocytic beta spectrin 2, a subunit of the spectrin heterotetramer. This gene is also associated with the disease autosomal recessive spinocerebellar ataxia 14 (MIM:615836, FBhh0000084). There is one high-scoring fly ortholog, β-Spec, for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and classical amorphic alleles have been generated.
Multiple UAS constructs of the human Hsap\SPTBN2 gene have been introduced into flies, including wild-type SPTBN2 and SPTBN2 genes carrying mutational lesions. Expression of the mutant forms in the adult eye causes a progressive neurodegenerative phenotype; expression in larval neurons results in posterior paralysis, reduced synaptic terminal growth, and axonal transport deficits.
Variant(s) implicated in human disease tested (as transgenic human gene, SPTBN2): the L253P (designated as Hsap\SPTBN2GM.UASp.Tag:MYC)and E532-M544 del(39bp del)(designated as Hsap\SPTBN2AM.UASp.Tag:MYC) variant forms of the human gene have been introduced into flies. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): not specified in the fly β-Spec gene (designated as β-SpecGM.UAS, corresponds to L253P in the human SPTBN2 gene); not specified in the fly β-Spec gene (designated as β-SpecAM.UAS, corresponds to E532-M544 del(39bp del)in the human SPTBN2 gene).
Homozygous loss-of-function mutations of Dmel\β-Spec are lethal, usually in late embryo or early larval stage; larval escapers have severely reduced synaptic transmission. Expression of the SCA5-comparable mutant forms results in phenotypes similar to those described above for the mutant human gene when expressed in flies. Physical and genetic interactions have been described for Dmel\β-Spec; see below and in the gene report for β-Spec.
[updated Mar. 2017 by FlyBase; FBrf0222196]
The autosomal dominant cerebellar degenerative disorders are generally referred to as 'spinocerebellar ataxias,' (SCAs) even though 'spinocerebellar' is a hybrid term, referring to both clinical signs and neuroanatomical regions (Margolis, 2003, pubmed:14628900). Neuropathologists have defined SCAs as cerebellar ataxias with variable involvement of the brainstem and spinal cord, and the clinical features of the disorders are caused by degeneration of the cerebellum and its afferent and efferent connections, which involve the brainstem and spinal cord (Schols et al., 2004 pubmed:15099544; Taroni and DiDonato, 2004, pubmed:15263894). [From MIM:164400, 2015.10.27]
The autosomal dominant cerebellar degenerative disorders are generally referred to as 'spinocerebellar ataxias' (SCAs). Neuropathologists have defined SCAs as cerebellar ataxias with variable involvement of the brainstem and spinal cord; the clinical features of the disorders are caused by degeneration of the cerebellum and its afferent and efferent connections, which involve the brainstem and spinal cord (Schols et al., 2004 pubmed:15099544; Taroni and DiDonato, 2004, pubmed:15263894). [From MIM:164400, 2015.10.27]
[SPINOCEREBELLAR ATAXIA 5; SCA5](https://omim.org/entry/600224)
[SPECTRIN, BETA, NONERYTHROCYTIC, 2; SPTBN2](https://omim.org/entry/604985)
Mean age at onset was 32.8 years (range, 15 to 50 years), with a tendency toward earlier onset in later generations. The most consistent clinical feature was downbeat nystagmus; 3 affected patients had downbeat nystagmus as an isolated feature. Other common features included gait, stance, and limb ataxia, dysarthria, intention tremor, resting tremor, impaired smooth pursuit, and gaze-evoked nystagmus. Symptom progression was slow, and all patients were ambulatory despite disease duration of up to 31 years. MRI showed atrophy of the cerebellar vermis and hemispheres (Burk et al., 2004, pubmed:14745083). [From MIM:600224, 2015.12.14]
This form of autosomal dominant spinocerebellar ataxia, SCA5, is caused by a heterozygous mutation in SPTBN2, the gene encoding spectrin, beta, non-erythrocytic 2. Homozygous mutation in the SPTBN2 gene causes autosomal recessive spinocerebellar ataxia-14 (SCAR14; MIM:615386). [From MIM:600224, 2015.10.29]
SPTBN2 is one of the subunits of spectrin, a heterotetramer made up of 2 alpha subunits and 2 beta subunits. Short actin filaments link spectrin tetramers together to form a flexible network that stabilizes cell contacts, channels, and adhesion molecules along the cytoplasmic face of membrane bilayers (summary by Clarkson et al., 2010, pubmed:20603325). [From MIM:604985, 2015.10.29]
Many to one (4 human to 1 Drosophila (See DIOPT, link below).
Ortholog of human SPTBN1, SPTB, SPTBN2, and SPTBN4 (1 Drosophila to 4 human; additional more distantly related genes in human).
Dmel\β-Spec shares 56% identity and 72% similarity with human SPTBN1, 48% identity and 66% similarity to human SPTN, 48% identity and 65% similarity to human SPTN2, and 40% identity and 56% similarity to human SPTN4.