SCA17 TBP

A rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I). It is characterized by a variable clinical picture which can include dementia, psychiatric disorders, parkinsonism, dystonia, chorea, spasticity, and epilepsy¹.

Prevalence

0.2 100,000

Unknown (global), <100 families, 0.47:1,000,000 (Japanese), 0.16/100,000 (England)^2,3: 0.2/100,000. Found across ethnicities/ancestries, with population-dependent prevalence².

Age of Onset Details

Typical: 19-48; Range: 3-62, has second variant to delay onset⁴.

Locus

hg19

chr6:170870995-170871105

hg38

chr6:170561907-170562017

t2t

chr6:171935459-171935569

Details

Benign range is 25-40 repeats, pathogenic range is 49+ repeats (largest to date 66 motifs, with mild correlation between size and age of onset), and intermediate alleles (41-48 repeats) are associated with reduced penetrance and potentially milder phenotypes². Huntington's disease like phenotype⁵. Interruptions seen: CAA⁶; CAA CAG CAA interruption is seen in all alleles stably transmitted across generations².

Mechanism

LoF/GoF

Polyglutamine expansion leading to transcriptional dysregulation⁷.

Year

1999⁸

Location in Gene

Exon 3

Gene Strand

Alleles

Ref. Motif

GCA

Pathogenic (ref.)

GCA

Pathogenic (gene)

AGC

gnomAD

Pathogenic genotype frequency data is not displayed for this locus because a substantial number of large alleles failed manual review by the gnomAD team.

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0011781

Spinocerebellar Ataxia Type 17

Yasuko,Toyoshima, Osamu,Onodera, Mitsunori,Yamada, Shoji,Tsuji, Hitoshi,Takahashi

GeneReviews® · 1993-01-01

genereviews:NBK1438

Profiling of Short-Tandem-Repeat Disease Alleles in 12,632 Human Whole Genomes.

Haibao,Tang, Ewen F,Kirkness, Christoph,Lippert, William H,Biggs, Martin,Fabani, Ernesto,Guzman, Smriti,Ramakrishnan, Victor,Lavrenko, Boyko,Kakaradov, Claire,Hou, Barry,Hicks, David,Heckerman, Franz J,Och, C Thomas,Caskey, J Craig,Venter, Amalio,Telenti

American journal of human genetics · 2017-11-02

pmid:29100084

omim:607136

Huntington's disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes.

Giovanni,Stevanin, Hiroto,Fujigasaki, Anne-Sophie,Lebre, Agnes,Camuzat, Cecile,Jeannequin, Catherine,Dode, Junko,Takahashi, Chankranira,San, Robert,Bellance, Alexis,Brice, Alexandra,Durr

Brain : a journal of neurology · 2003-05-06

pmid:12805114

Comprehensive genetic diagnosis of tandem repeat expansion disorders with programmable targeted nanopore sequencing.

Igor,Stevanovski, Sanjog R,Chintalaphani, Hasindu,Gamaarachchi, James M,Ferguson, Sandy S,Pineda, Carolin K,Scriba, Michel,Tchan, Victor,Fung, Karl,Ng, Andrea,Cortese, Henry,Houlden, Carol,Dobson-Stone, Lauren,Fitzpatrick, Glenda,Halliday, Gianina,Ravenscroft, Mark R,Davis, Nigel G,Laing, Avi,Fellner, Marina,Kennerson, Kishore R,Kumar, Ira W,Deveson

Science advances · 2022-03-04

pmid:35245110

Molecular Mechanisms in Pentanucleotide Repeat Diseases.

Joana R,Loureiro, Ana F,Castro, Ana S,Figueiredo, Isabel,Silveira

Cells · 2022-01-08

pmid:35053321

A neurological disease caused by an expanded CAG trinucleotide repeat in the TATA-binding protein gene: a new polyglutamine disease?

R,Koide, S,Kobayashi, T,Shimohata, T,Ikeuchi, M,Maruyama, M,Saito, M,Yamada, H,Takahashi, S,Tsuji

Human molecular genetics · 1999-10-01

pmid:10484774

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

ATXN10 Gene Expansions in Mexican Patients with Ataxia Without Epilepsy.

Aurelio,Jara-Prado, Eukeni,Arias-Capistran, Jorge,Guerrero-Camacho, Adriana,Ochoa-Morales, Marie Catherine,Boll, David,Dávila-Ortíz de Montellano, Astrid,Rasmussen, Tetsuo,Ashizawa, Juan,Fernandez-Ruiz, Petra,Yescas-Gómez, Miguel Ángel,Ramírez-García

Cerebellum (London, England) · 2025-01-16

pmid:39820777

Case Series of Cerebellar Ataxia with Tremor Due to Heterozygous STUB1 Variants (SCA48) without TBP Expansions: Further Evidence for SCA48 as a Monogenic Disease.

Yan,Zochowski, Kishore R,Kumar, Matthew,Katz, Paul,Darveniza, Michel,Tchan, Renee,Smyth, Susan,Tomlinson, Kathy H C,Wu, Stephen,Tisch

Cerebellum (London, England) · 2024-12-16

pmid:39680235

Identification and Copy Number Variant Analysis of Enhancer Regions of Genes Causing Spinocerebellar Ataxia.

Fatemeh,Ghorbani, Eddy N,de Boer, Michiel R,Fokkens, Jelkje,de Boer-Bergsma, Corien C,Verschuuren-Bemelmans, Elles,Wierenga, Hamidreza,Kasaei, Daan,Noordermeer, Dineke S,Verbeek, Helga,Westers, Cleo C,van Diemen

International journal of molecular sciences · 2024-10-18

pmid:39456985

The New Face of Dynamic Mutation-The CAA [CAG]n CAA CAG Motif as a Mutable Unit in the

Dorota,Hoffman-Zacharska, Anna,Sulek

International journal of molecular sciences · 2024-07-26

pmid:39125760

A New Case Series Suggests That SCA48 (ATX/STUB1) Is Primarily a Monogenic Disorder.

Teije H,van Prooije, Maartje,Pennings, Lucille,Dorresteijn, Thatjana,Gardeitchik, Vincent J J,Odekerken, Mayke,Oosterloo, Annie,Pedersen, Corien C,Verschuuren-Bemelmans, Alexander,Vrancken, Erik-Jan,Kamsteeg, Bart P C,van de Warrenburg

Movement disorders : official journal of the Movement Disorder Society · 2024-07-07

pmid:38973070

Tremor-associated short tandem repeat intermediate and pathogenic expansions in familial essential tremor.

Xun,Zhou, Runcheng,He, Sheng,Zeng, Mingqiang,Li, Hongxu,Pan, Yuwen,Zhao, Zhenhua,Liu, Qian,Xu, Jifeng,Guo, Xinxiang,Yan, Jinchen,Li, Beisha,Tang, Qiying,Sun

Brain communications · 2024-06-29

pmid:38961870

Cognitive dysfunction, social behavior disorder, cerebellar ataxia, and atypical brain FDG-PET presentation in spinocerebellar ataxia 17: a case report.

Alberto,Grassini, Aurora,Cermelli, Fausto,Roveta, Michela,Zotta, Adriana,Lesca, Andrea,Marcinnò, Fabio,Ferrandes, Elisa,Piella, Silvia,Boschi, Chiara,Lombardo, Alfredo,Brusco, Salvatore,Gallone, Elisa,Rubino, Amalia,Bruni, Innocenzo,Rainero

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024-03-18

pmid:38494459

Dilemma in differentiation of spinocerebellar ataxia type 17 from Huntington's disease: comorbidity or independent disease?

Li,An, Sheng,Yao, Jianguo,Liu, Xiaokun,Qi, Feng,Duan, Chenjing,Sun

The International journal of neuroscience · 2023-10-31

pmid:37855597

A DLB patient with complicated CAA interruptions and intermediate alleles of 43 CAG/CAA repeats in TBP.

Zhiru,Lin, Jiaxiang,Li, Wei,Luo

Acta neurologica Belgica · 2023-08-26

pmid:37632648