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FB2026_01
,
released March 12, 2026
This report describes spinocerebellar ataxia 19 (SCA19), also designated spinocerebellar ataxia 19/22 (SCA19/22); SCA19 exhibits autosomal dominant inheritance. The human gene implicated in this disease is KCND3, which encodes a component of a voltage-activated A-type potassium ion channel (shal-related subfamily). There is a single orthologous gene in Drosophila, Shal, for which multiple genetic reagents have been generated, including RNAi-targeting constructs, overexpression constructs, and alleles caused by insertional mutagenesis.
Adult animals with RNAi-mediated pan-neuronal knockdown of Dmel\Shal exhibit severe locomotor dysfunction in a climbing assay. RNAi-mediated knockdown of Shal in the developing eye results in an age-dependent progressive phenotype affecting the structure of the ommatidia.
Multiple UAS constructs of the human Hsap\KCND3 gene have been introduced into flies, including wild-type and variants implicated in this disease; see the 'Disease-Implicated Variants' table below. Heterologous rescue (functional complementation) has been demonstrated for the locomotor dysfunction phenotype observed for animals with Shal pan-neuronal knockdown and for the eye phenotype of eye-specific Shal knockdown. Disease-implicated variants of Hsap\KCND3 have been characterized in the Drosophila system; results support the hypothesis that two variants tested act as dominant-negatives.
[updated Jun. 2025 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 19; SCA19](https://omim.org/entry/607346)
[POTASSIUM VOLTAGE-GATED CHANNEL, SHAL-RELATED SUBFAMILY, MEMBER 3; KCND3](https://omim.org/entry/605411)
Spinocerebellar ataxia-19 (SCA19) is an autosomal dominant disorder characterized by progressive cerebellar ataxia with a variable age of onset (age 2 years to late adulthood). Other neurologic manifestations include developmental delay and cognitive impairment; movement disorders including myoclonus, dystonia, rigidity, and bradykinesia; and seizures. [from MIM:607346; 2025.06.03]
Spinocerebellar ataxia-19 (SCA19), also known as SCA22, is caused by heterozygous mutation in the KCND3 gene. [from MIM:607346; 2025.06.03]
KCND3 encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. The encoded protein is a pore-forming (alpha) subunit of voltage-gated A-type potassium channels that mediates transmembrane potassium transport in excitable membranes. [GeneCards, KCND3; 2025.06.03]
One to one: 1 human gene to 1 Drosophila gene; multiple related genes in both species.
High-scoring ortholog of human KCND3 (1 Drosophila to 1 human; multiple related genes in both species).