Human Disease Model Report: spinocerebellar ataxia 17

General Information

Name

spinocerebellar ataxia 17

FlyBase ID

FBhh0000071

Disease Ontology Term

spinocerebellar ataxia 17

Parent Disease

spinocerebellar ataxia, autosomal dominant

OMIM

SPINOCEREBELLAR ATAXIA 17; SCA17

Overview

This report describes spinocerebellar ataxia 17 (SCA17), which is a subtype of spinocerebellar ataxia; SCA17 is inherited as an autosomal dominant. The human gene implicated in this disease is TBP, which encodes TATA box-binding protein, DNA-binding subunit of the RNA polymerase II transcription factor D. Expanded (CAG)n or (CAA)n trinucleotide repeats encoding polyglutamine in TBP are associated with SCA17; SCA17 is one of a number spinocerebellar ataxias caused by expansion of such repeats within the coding region of the causative gene. There is one high-scoring fly ortholog, Tbp, for which RNAi targeting constructs, alleles caused by insertional mutagenesis, and classical amorphic alleles have been generated. Dmel\Tbp is orthologous to a second human gene, TBPL2.

Multiple UAS constructs of the human gene Hsap\TBP have been introduced into flies, including wild-type TBP, and TBP genes with expanded polyglutamine repeats. Transgenic flies expressing a mutant Hsap\TBP protein with an expanded polyQ tract exhibit progressive neurodegeneration, late-onset locomotor impairment and shortened lifespan. Expression in the eye results in a neurodegenerative phenotype; this phenotype has been used to assess genetic interactions.

Variant(s) implicated in human disease tested (as transgenic human gene, TBP): Q58_Q95 (CAG)n EXPANSION; UAS-TBP constructs with differing numbers of the pathological trinucleotide repeat have been created.

Animals homozygous for loss-of-function alleles of Dmel\Tbp die during larval stages. Heterozygous animals can survive to adulthood without obvious morphological defects, but suffer severe locomotor defects and a shortened lifespan. Physical and genetic interactions for Dmel\Tbp have been reported; see below and in the gene report for Tbp.

Extensive studies have also been done with polyglutamine-only models in flies; see the disease report for polyglutamine diseases, polyQ models (FBhh0000001).

[updated Mar. 2017 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 MIM:164400, 2015.10.27]

(OMIM, 2013-)

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]

(FlyBase Curators, 2013-)

Specific Disease Summary: spinocerebellar ataxia 17

OMIM report

[SPINOCEREBELLAR ATAXIA 17; SCA17](https://omim.org/entry/607136)

Human gene(s) implicated

[TATA BOX-BINDING PROTEIN; TBP](https://omim.org/entry/600075)

Symptoms and phenotype

Spinocerebellar ataxia type 17 (SCA17) is characterized by ataxia, dementia, and involuntary movements, including chorea and dystonia. Psychiatric symptoms, pyramidal signs, and rigidity are common. The age of onset ranges from three to 55 years. Individuals with full-penetrance alleles develop neurologic and/or psychiatric symptoms by age 50 years. Ataxia and psychiatric abnormalities are frequently the initial findings, followed by involuntary movement, parkinsonism, dementia, and pyramidal signs. Brain MRI shows variable atrophy of the cerebrum, brain stem, and cerebellum. The clinical features correlate with the length of the polyglutamine expansion but are not absolutely predictive of the clinical course. [From GeneReviews, Spinocerebellar Ataxia Type 17, pubmed:20301611, 2015.12.15]

(FlyBase Curators, 2013-)

SCA17 is an autosomal dominant neurologic disorder characterized by ataxia, pyramidal and extrapyramidal signs, cognitive impairments, psychosis, and seizures. Its clinical phenotype and inheritance pattern are similar to Huntington disease (HD; MIM:143100). Individuals with normal TBP alleles have between 25 and 44 repeats, whereas SCA17 patients have between 47 and 63 repeats. Reduced penetrance is seen with 45 to 46 repeats (summary by Gao et al., 2008, pubmed:18043721). [From MIM:607136, 2015.12.15]

(OMIM, 2013-)

Genetics

This form of autosomal dominant spinocerebellar ataxia, SCA17 can be caused by heterozygous expansion of a trinucleotide repeat encoding glutamine (CAG or CAA) in TBP, the gene encoding the TATA box-binding protein. Rarely, SCA17 has been found to be caused by homozygous or compound heterozygous TBP repeat expansions. [From MIM:607136, 2015.10.30]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

TBP is the DNA-binding subunit of the RNA polymerase II transcription factor D (TFIID; see MIM:313650), a multisubunit complex essential for the expression of most, if not all, protein-encoding genes. [From MIM:600075, 2015.10.30]

(OMIM, 2013-)

External links

Gene2Function (human gene): TBP
Gene Cards: TBP
GeneReviews, NCBI Bookshelf: Spinocerebellar Ataxia Type 17
MedlinePlus (condition): Huntington disease-like syndrome
MedlinePlus (gene): TBP
MARRVEL (human gene): TBP
NCBI MedGen: Spinocerebellar ataxia 17 (SCA17)
NCBI (Entrez) gene: TBP; TATA-box binding protein
National Organization for Rare Disorders: Autosomal Dominant Hereditary Ataxia

Disease synonyms

HDL4

Huntington-disease-like 4

SCA17

spinocerebellar ataxia 17; SCA17

spinocerebellar ataxia type 17

Related Diseases

Related human health report(s)

polyglutamine diseases

polyglutamine diseases, polyQ models

Related Specific Diseases

OMIM phenotypic series

Spinocerebellar ataxia

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

[MJD](https://omim.org/entry/109150)

[ATXN3](https://omim.org/entry/607047)

Machado-Joseph disease (SCA3)

[SCA1](https://omim.org/entry/164400)

[ATXN1](https://omim.org/entry/601556)

spinocerebellar ataxia 1

[SCA2](https://omim.org/entry/183090)

[ATXN2](https://omim.org/entry/601517)

spinocerebellar ataxia 2

[SCA5](https://omim.org/entry/600224)

[SPTBN2](https://omim.org/entry/604985)

spinocerebellar ataxia 5

[SCA6](https://omim.org/entry/183086)

[CACNA1A](https://omim.org/entry/601011)

spinocerebellar ataxia 6

[SCA7](https://omim.org/entry/164500)

[ATXN7](https://omim.org/entry/607640)

spinocerebellar ataxia 7

[SCA8](https://omim.org/entry/608768)

[ATXN8](https://omim.org/entry/613289)

spinocerebellar ataxia 8

[SCA8](https://omim.org/entry/608768)

[ATXN8OS](https://omim.org/entry/603680)

spinocerebellar ataxia 8

[SCA10](https://omim.org/entry/603516)

[ATXN10](https://omim.org/entry/611150)

spinocerebellar ataxia 10

[SCA11](https://omim.org/entry/604432)

[TTBK2](https://omim.org/entry/611695)

[SCA12](https://omim.org/entry/604326)

[PPP2R2B](https://omim.org/entry/604325)

spinocerebellar ataxia 12

[SCA13](https://omim.org/entry/605259)

[KCNC3](https://omim.org/entry/176264)

spinocerebellar ataxia 13

[SCA14](https://omim.org/entry/605361)

[PRKCG](https://omim.org/entry/176980)

spinocerebellar ataxia 14

[SCA15](https://omim.org/entry/606658)

[ITPR1](https://omim.org/entry/147265)

spinocerebellar ataxia 15

[SCA17](https://omim.org/entry/607136)

[TBP](https://omim.org/entry/600075)

spinocerebellar ataxia 17

[SCA19](https://omim.org/entry/607346)

[KCND3](https://omim.org/entry/605411)

spinocerebellar ataxia 19

[SCA28](https://omim.org/entry/610246)

[AFG3L2](https://omim.org/entry/604581)

spinocerebellar ataxia 28

[SCA29](https://omim.org/entry/117360)

[ITPR1](https://omim.org/entry/147265)

spinocerebellar ataxia 29

[SCA31](https://omim.org/entry/117210)

[BEAN1](https://omim.org/entry/612051)

spinocerebellar ataxia 31

[SCA35](https://omim.org/entry/613908)

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

spinocerebellar ataxia 35

Ortholog Information

Human gene(s) in FlyBase

Hsap\TBP

Human gene (HGNC)

Symbol / Name

TBP; TATA-box binding protein

D. melanogaster ortholog (based on DIOPT)

Dmel\Tbp

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one (2 human to 1 Drosophila) (See DIOPT, link below)

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\Tbp

Gene Snapshot

TATA binding protein (Tbp) encodes a basal transcription factor required at most RNA Pol I and Pol II-transcribed genes. Traditionally thought to be recruited only to TATA box containing promoters, recent work shows that promoters with very weak TATA box consensus sequences also recruit the product of Tbp as a part of the multisubunit TFIID basal transcription factor or via the SAGA histone acetyltransferase complex. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

TRF
TFIID

Comments on ortholog(s)

Ortholog of human ITPR1, and ITPR3 (1 Drosophila to 2 human).

Dmel\Tbp shares 58% identity and 63% similarity with human TBP, and 54% identity and 62% similarity to human TBPL2.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (44 groups)

Tbp

protein-protein

Interacting group

Assay

References

Tbp - Ada2a

anti bait coimmunoprecipitation, western blot

(Lebedeva et al., 2004, Muratoglu et al., 2003)

Tbp - Ada2b

anti bait coimmunoprecipitation, western blot

(Lebedeva et al., 2004, Muratoglu et al., 2003)

Tbp - Antp

fluorescent resonance energy transfer, fluorescence microscopy

(Villarreal-Puente et al., 2024)

Tbp - apt

anti bait coimmunoprecipitation, western blot

(Liu et al., 2003)

Tbp - Bap60

ion exchange chromatography, molecular sieving, western blot

(Vorobyeva et al., 2009)

Tbp - Bdp1

protein cross-linking with a bifunctional reagent, Identification by mass spectrometry

(Kim et al., 2020)

Tbp - Brd8

anti tag coimmunoprecipitation, anti tag western blot

(Shen et al., 2025)

Tbp - Brf

two hybrid, anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based

(Hu et al., 2017.6.13, Rhee et al., 2014)

Tbp - CG9890

anti bait coimmunoprecipitation, western blot

(Fursova et al., 2018)

Tbp - CREG

two hybrid

(Veal et al., 1998)

Tbp - CycT

anti tag coimmunoprecipitation, anti tag western blot

(Shen et al., 2025)

Tbp - dom

anti tag coimmunoprecipitation, anti tag western blot

(Shen et al., 2025)

Tbp - e(y)2

anti bait coimmunoprecipitation, western blot

(Georgieva et al., 2001)

Tbp - e(y)3

anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, ion exchange chromatography, molecular sieving

(Vorobyeva et al., 2009, Soshnikova et al., 2008, Vorobyeva et al., 2008)

Tbp - Gcn5

anti bait coimmunoprecipitation, western blot

(Soffers et al., 2021)

Tbp - Hel89B

anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based

(Rhee et al., 2014)

Tbp - lilli

anti tag coimmunoprecipitation, anti tag western blot

(Shen et al., 2025)

Tbp - mahj

anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based

(Rhee et al., 2014)

Tbp - mbf1

pull down, western blot, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation

(Liu et al., 2003)

Tbp - Mef2

anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation

(Clark et al., 2013)

Tbp - mor

ion exchange chromatography, molecular sieving, western blot

(Vorobyeva et al., 2009)

Tbp - MTF-1

pull down, western blot

(Marr et al., 2012)

Tbp - Pbp45

protein cross-linking with a bifunctional reagent, Identification by mass spectrometry

(Kim et al., 2020)

Tbp - Pc

anti bait coimmunoprecipitation, western blot

(Breiling et al., 2001, Saurin et al., 2001)

Tbp - ph-p

anti bait coimmunoprecipitation, western blot

(Breiling et al., 2001, Saurin et al., 2001)

Tbp - Polr2A

anti bait coimmunoprecipitation, western blot

(Cernilogar et al., 2011)

Tbp - polybromo

ion exchange chromatography, molecular sieving, western blot

(Vorobyeva et al., 2009)

Tbp - Psc

anti bait coimmunoprecipitation, western blot

(Breiling et al., 2001, Saurin et al., 2001)

Tbp - Taf1

anti bait coimmunoprecipitation, western blot, pull down, affinity chromatography technology, anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based, molecular weight estimation by staining, ion exchange chromatography, molecular sieving

(Rhee et al., 2014, Vorobyeva et al., 2009, Katzenberger et al., 2006, Santoso and Kadonaga, 2006, Georgieva et al., 2001, Chen et al., 1994, Kokubo et al., 1994, Verrijzer et al., 1994, Yokomori et al., 1993)

Tbp - Taf2

anti bait coimmunoprecipitation, molecular weight estimation by staining, anti tag coimmunoprecipitation, western blot, autoradiography

(Chen et al., 1994, Verrijzer et al., 1994, Yokomori et al., 1993)

Tbp - Taf4

anti bait coimmunoprecipitation, western blot, molecular weight estimation by staining

(Wright et al., 2006, Georgieva et al., 2001, Saurin et al., 2001, Chen et al., 1994, Verrijzer et al., 1994, Kokubo et al., 1993, Yokomori et al., 1993)

Tbp - Taf5

anti bait coimmunoprecipitation, western blot, molecular weight estimation by staining

(Saurin et al., 2001, Chen et al., 1994, Verrijzer et al., 1994, Yokomori et al., 1993)

Tbp - Taf6

anti bait coimmunoprecipitation, western blot, molecular weight estimation by staining, anti tag coimmunoprecipitation, peptide massfingerprinting

(Weake et al., 2009, Wright et al., 2006, Chen et al., 1994, Verrijzer et al., 1994, Yokomori et al., 1993)

Tbp - Taf9

anti bait coimmunoprecipitation, western blot, ion exchange chromatography, molecular sieving, molecular weight estimation by staining

(Vorobyeva et al., 2009, Georgieva et al., 2001, Saurin et al., 2001, Chen et al., 1994, Verrijzer et al., 1994, Goodrich et al., 1993, Yokomori et al., 1993)

Tbp - Taf10

anti bait coimmunoprecipitation, western blot

(Lebedeva et al., 2004, Muratoglu et al., 2003, Georgieva et al., 2001)

Tbp - Taf10b

anti bait coimmunoprecipitation, western blot

(Lebedeva et al., 2004, Muratoglu et al., 2003)

Tbp - Taf11

anti bait coimmunoprecipitation, molecular weight estimation by staining, western blot, peptide massfingerprinting

(Chen et al., 1994, Verrijzer et al., 1994, Yokomori et al., 1993)

Tbp - Taf12

anti bait coimmunoprecipitation, molecular weight estimation by staining, western blot, anti tag coimmunoprecipitation, peptide massfingerprinting

(Chen et al., 1994, Verrijzer et al., 1994, Yokomori et al., 1993)

Tbp - Taf105

anti bait coimmunoprecipitation, western blot

(Vilalta et al., 1997)

Tbp - TfIIA-L

pull down, autoradiography, anti tag coimmunoprecipitation, anti tag western blot

(Yokomori et al., 1994, Yokomori et al., 1993)

Tbp - TfIIA-S

pull down, autoradiography

(Yokomori et al., 1994)

Tbp - Ubx

fluorescent resonance energy transfer, fluorescence microscopy, bimolecular fluorescence complementation

(Villarreal-Puente et al., 2024)

Hsap\TBP

protein-protein

Interacting group

Assay

References

Hsap\TBP - Antp

fluorescent resonance energy transfer, fluorescence microscopy

(Jiménez-Mejía et al., 2022)

Hsap\TBP - Su(H)

anti bait coimmunoprecipitation, western blot

(Ren et al., 2011)

Alleles Reported to Model Human Disease (Disease Ontology) (6 alleles)

Tbp

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

Tbp^sI10

model of neurodegenerative disease

CEA

(Hsu et al., 2014)

Modifiers Based on Experimental Evidence ( 2 )

Allele

Disease

Interaction

References

Tbp^sI10

exacerbates autosomal dominant cerebellar ataxia

modeled by Hsap\TBP^{109Q.UAS.Tag:HA}

(Hsu et al., 2014)

exacerbates Huntington's disease

modeled by Hsap\HTT^Q97.ex1.UAS

(Hsu et al., 2014)

exacerbates Machado-Joseph disease

modeled by Hsap\ATXN3^{tr.Q78.UAS.Tag:HA}

(Hsu et al., 2014)

Tbp^UAS.cHa

exacerbates autosomal dominant cerebellar ataxia

modeled by Hsap\TBP^{109Q.UAS.Tag:HA}

(Hsu et al., 2014)

exacerbates Huntington's disease

modeled by Hsap\HTT^Q97.ex1.UAS

(Hsu et al., 2014)

exacerbates Machado-Joseph disease

modeled by Hsap\ATXN3^{tr.Q78.UAS.Tag:HA}

(Hsu et al., 2014)

Hsap\TBP

Models Based on Experimental Evidence ( 4 )

Allele

Disease

Evidence

References

Hsap\TBP^80Q.UAS

model of autosomal dominant cerebellar ataxia

CEA

(Ren et al., 2011)

Hsap\TBP^{109Q.UAS.Tag:HA}

model of autosomal dominant cerebellar ataxia

CEA

(Hsu et al., 2014)

model of spinocerebellar ataxia 17

CEA

(Yeh et al., 2018)

Hsap\TBP^{63Q.UAS.Tag:HA}

model of spinocerebellar ataxia 17

CEA

(Patel et al., 2023)

Hsap\TBP^80Q.UAS.cMa

model of spinocerebellar ataxia 17

CEA

(Montalvo-Méndez et al., 2024)

Modifiers Based on Experimental Evidence ( 2 )

Allele

Disease

Interaction

References

Hsap\TBP^80Q.UAS

model of autosomal dominant cerebellar ataxia

is exacerbated by Su(H)^VDRC.cUa

(Ren et al., 2011)

is ameliorated by Su(H)^UAS.Tag:MYC

(Ren et al., 2011)

is exacerbated by Su(H)^RNAi.UAS.cUa

(Ren et al., 2011)

Hsap\TBP^{109Q.UAS.Tag:HA}

model of autosomal dominant cerebellar ataxia

is exacerbated by Tbp^sI10

(Hsu et al., 2014)

is exacerbated by Tbp^UAS.cHa

(Hsu et al., 2014)

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

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Hsap\TBP^UAS.Tag:HA

P{UAS-hTBP.HA}

Hsap\TBP^{63Q.UAS.Tag:HA}

Hsap\TBP^UAS.1.Tag:HA

Hsap\TBP^{36Q.UAS.Tag:HA}

P{UAS-Hsap\TBP-HA.36Q}

Hsap\TBP^{109Q.UAS.Tag:HA}

P{UAS-Hsap\TBP-HA.109Q}

Hsap\TBP^{36Q.UAS.Tag:FLAG}

P{UAS-Hsap\TBP-FLAG.36Q}

Hsap\TBP^{N.36Q.UAS.Tag:MYC}

P{UAS-Hsap\TBP-MYC.N.36Q}

Hsap\TBP^{N.109Q.UAS.Tag:MYC}

P{UAS-Hsap\TBP-MYC.N.109Q}

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

Tbp^UAS.cHa

P{UAS-Tbp.H}

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

y¹ v¹; P{TRiP.GL00726}attP2

Tbp^HMC04197

P{TRiP.HMC04197}

y¹ sc^* v¹ sev²¹; P{TRiP.HMC04197}attP40

Tbp^VSH330174

P{VSH330174}

P{VSH330174}attP40

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

Tbp^KO

loss of function allele

CRISPR/Cas9

Tbp^sI10

ethyl methanesulfonate

References (18)

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