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General Information
Name
spinocerebellar ataxia 35
FlyBase ID
FBhh0000789
Overview

This report describes spinocerebellar ataxia 35 (SCA35), which is a subtype of spinocerebellar ataxia; SCA35 exhibits autosomal dominant inheritance. The human gene implicated in this disease is transglutaminase 6 (TGM6), which encodes one of nine transglutaminases in human; transglutaminases catalyze the cross-linking of proteins and the conjugation of polyamines to proteins. The single transglutaminase in Drosophila, Tg, is more closely related to other human genes in this family.

Multiple tagged UAS constructs of the human Hsap\TGM6 gene have been introduced into flies, including wild-type and a variant implicated in SCA35. Variant(s) implicated in human disease tested (as transgenic human gene, TGM6): the R111C variant form has been introduced into flies. Results support findings in mammalian systems that the R111C variant exhibits an increased rate of protein turnover.

[updated Apr. 2018 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: spinocerebellar ataxia, autosomal dominant
Symptoms and phenotype

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 OMIM: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 OMIM:164400, 2015.10.27]

Specific Disease Summary: spinocerebellar ataxia 35
OMIM report

[SPINOCEREBELLAR ATAXIA 35; SCA35](https://omim.org/entry/613908)

Human gene(s) implicated

[TRANSGLUTAMINASE 6; TGM6](https://omim.org/entry/613900)

Symptoms and phenotype

Spinocerebellar ataxia 35 is an autosomal dominant adult-onset neurologic disorder characterized by difficulty walking due to cerebellar ataxia. The age at onset ranges from teenage years to late adulthood, and the disorder is slowly progressive. Additional features may include hand tremor, dysarthria, hyperreflexia, and saccadic eye movements (summary by Guo et al., 2014; pubmed:25253745). [from OMIM:613908; 2018.04.16]

Genetics

Autosomal dominant spinocerebellar ataxia 35 (SCA35) is caused by heterozygous mutation in the TGM6 gene.

Cellular phenotype and pathology
Molecular information

The protein encoded by TGM6 belongs to the transglutaminase superfamily. It catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. [Gene Cards, TGM6; 2018.04.16]

Transglutaminases covalently crosslink or modify proteins by formation of an isopeptide bond between a peptide-bound glutamine and a primary amine, most commonly a lysine, either within the same or a neighboring polypeptide. Transglutaminases may also react with water, leading to the deamidation of glutamine residues (summary by Hadjivassiliou et al., 2008; pubmed:18825674). [from OMIM:613900; 2018.04.16]

External links
Disease synonyms
SCA35
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to one: 9 human to 1 Drosophila. Dmel\Tg is a low-scoring ortholog of TGM6; it is more closely related to other human transglutaminases.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (0)
    Other Genes Used: Viral, Bacterial, Synthetic (0)
      Summary of Physical Interactions (0 groups)
      Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)
      Models Based on Experimental Evidence ( 2 )
      Modifiers Based on Experimental Evidence ( 0 )
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      Alleles Representing Disease-Implicated Variants
      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
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      Selected Drosophila transgenes
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      Publicly Available Stocks
      RNAi constructs available
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      Selected Drosophila classical alleles
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      Publicly Available Stocks
      References (5)