The report describes spinocerebellar ataxia autosomal recessive 21 (SCAR21), a neurodegenerative disease that is also associated with liver dysfunction. The human gene implicated in SCAR21 is SCYL1, a transcriptional regulator that impacts retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum. There is a single orthologous gene in Drosophila, yata, for which multiple genetic reagents have been generated, including an amorphic mutation, RNAi-targeting constructs, and alleles caused by insertional mutagenesis.
The human SCYL1 has not been introduced into flies.
Animals homozygous for an amorphic mutation of yata exhibit developmental abnormalities, progressive eye vacuolization, brain volume reduction, and shortened lifespan. Work in flies has addressed the role of yata in the proper localization of components the COPI coat protein complex in organelles that are involved in vesicular trafficking. Assayed in neural tissues, yata mutants also show impaired subcellular localization of Appl (see FBhh0000119). A small number of physical and genetic interactions have been described for Dmel\yata; see below and in the yata gene report.
[updated Apr. 2021 by FlyBase; FBrf0222196]
Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years (Palau and Espinos, 2006; pubmed:17112370).
The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. [from Gene Reviews, Hereditary Ataxia Overview; pubmed:20301317; 2017.06.16]
See also Jayadev and Bird, 2013 (pubmed:23538602).
Autosomal recessive spinocerebellar ataxia is a neurologic disorder characterized by onset of progressive gait difficulties, eye movement abnormalities, and dysarthria in the first or second decade of life (summary, Dy et al, 2105; pubmed:26224725). [from MIM:609270; 2020.07.13]
[SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 21; SCAR21](https://omim.org/entry/616719)
[SCY1-LIKE 1; SCYL1](https://omim.org/entry/607982)
Autosomal recessive spinocerebellar ataxia-21 is a neurologic disorder characterized by onset of cerebellar ataxia associated with cerebellar atrophy in early childhood. Affected individuals also have recurrent episodes of liver failure in the first decade, resulting in chronic liver fibrosis, as well as later onset of a peripheral neuropathy. Mild learning disabilities may also occur (summary by Schmidt et al., 2015; pubmed:26581903). The phenotype is highly variable: all patients appear to have episodic and severe liver dysfunction in early childhood that tends to resolve with age. Affected individuals also show mild developmental or language delay and/or later onset of variable neurologic features, such as motor dysfunction (summary by Lenz et al., 2018; pubmed:29419818). [from MIM:616719; 2021.04.05]
Autosomal recessive spinocerebellar ataxia-21 (SCAR21) is caused by homozygous mutation in the SCYL1 gene. [from MIM:616719; 2021.04.05]
SCYL1 encodes a transcriptional regulator belonging to the SCY1-like family of kinase-like proteins. The protein has a divergent N-terminal kinase domain that is thought to be catalytically inactive, and can bind specific DNA sequences through its C-terminal domain. Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum. [Gene Cards, SCYL1; 2021.04.05]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human SCYL1 (1 Drosophila to 1 human). Dmel\yata shares 44% identity and 57% similarity with the human gene.
