Spinocerebellar ataxia type 1 (SCA1) is a subtype of type I autosomal dominant cerebellar ataxia (ADCA type I) characterized by dysarthria, writing difficulties, limb ataxia, and commonly nystagmus and saccadic abnormalities¹.

Prevalence

1.5 100,000

1-2/100,000. Cases have been reported worldwide, although prevalence varies by ancestry/ethnicity².

Age of Onset

Typical: 20-39³; Range: 6⁴- 63⁵.

HPO Terms

–

Association

Mendelian

Locus

hg19 chr6:16327864-16327955

hg38 chr6:16327633-16327724

t2t chr6:16200188-16200282

Details

Penetrance is dependent on sequence purity in addition to expansion length: pure repeats are pathogenic at 39 repeats⁶, while CAT interruptions⁷can lead to reduced penetrance at comparable lengths². Regardless, intermediate alleles are considered premutations which may lead to disease upon transmission². CAA interruptions have also been reported, but not linked to any phenotypic consequences⁸.

Mechanism

GoF/LoF

Polyglutamine expansion leading to toxic gain of function with eventual misregulation-based loss of function/dominant negative^2,9.

Detection

PCR fragment analysis is commonly used for sizing [@genereviews:NBK1184]. Standard fragment analysis does not resolve CAT interruptions, which require targeted analysis like RP-PCR or Sanger sequencing [@pmid:34635619; @genereviews:NBK1184].

Year

1993¹⁰

Location in Gene

Coding Exon 8

Gene Strand

Alleles

Ref. Motif

CTG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CTG

Pathogenic (gene)

AGC

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

ATG, TTG

Interruption (gene)

ATC, AAC

gnomAD

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0008119

Spinocerebellar Ataxia Type 1

Puneet,Opal, Tetsuo,Ashizawa

GeneReviews® · 1993-01-01

genereviews:NBK1184

UpToDate

url:https://www.uptodate.com/contents/autosomal-dominant-spinocerebellar-ataxias

Spinocerebellar ataxia: variable age of onset and linkage to human leukocyte antigen in a large kindred.

H Y,Zoghbi, M S,Pollack, L A,Lyons, R E,Ferrell, S P,Daiger, A L,Beaudet

Annals of neurology · 1988-06-01

pmid:3165612

Clinical features and natural history of spinocerebellar ataxia type 1.

H,Sasaki, T,Fukazawa, T,Yanagihara, T,Hamada, K,Shima, A,Matsumoto, K,Hashimoto, N,Ito, A,Wakisaka, K,Tashiro

Acta neurologica Scandinavica · 1996-01-01

pmid:8825276

The Frequency of Intermediate Alleles in Patients with Cerebellar Phenotypes.

Elena,Capacci, Silvia,Bagnoli, Giulia,Giacomucci, Costanza Maria,Rapillo, Alessandra,Govoni, Valentina,Bessi, Cristina,Polito, Irene,Giotti, Alice,Brogi, Elisabetta,Pelo, Sandro,Sorbi, Benedetta,Nacmias, Camilla,Ferrari

Cerebellum (London, England) · 2023-10-31

pmid:37906407

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

The role of interruptions in polyQ in the pathology of SCA1.

Rajesh P,Menon, Suran,Nethisinghe, Serena,Faggiano, Tommaso,Vannocci, Human,Rezaei, Sally,Pemble, Mary G,Sweeney, Nicholas W,Wood, Mary B,Davis, Annalisa,Pastore, Paola,Giunti

PLoS genetics · 2013-07-25

pmid:23935513

Combined overexpression of ATXN1L and mutant ATXN1 knockdown by AAV rescue motor phenotypes and gene signatures in SCA1 mice.

Ellie M,Carrell, Megan S,Keiser, Ashley B,Robbins, Beverly L,Davidson

Molecular therapy. Methods & clinical development · 2022-04-12

pmid:35573049

Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1.

H T,Orr, M Y,Chung, S,Banfi, T J,Kwiatkowski, A,Servadio, A L,Beaudet, A E,McCall, L A,Duvick, L P,Ranum, H Y,Zoghbi

Nature genetics · 1993-07-01

pmid:8358429

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)

Computational Short Tandem Repeat Genotyping Reveals Clinically Relevant Expansions in a Large Turkish Neurodegeneration Disease Cohort.

Zakhiriddin,Khojakulov, Robin J,Palvadeau, Müge,Kovancılar-Koç, Irmak,Atay, Irmak,Şahbaz, Şeyma,Tekgül, Ayça,Şahin, Esmer Zeynep Duru,Badakal, Tuğçe,Gül-Demirkale, Vildan,Çiftçi, Elif,Bayraktar, Ceren,Tunca, Natalia,Smolina, Fulya,Akçimen, Ayşe Nazlı,Başak

International journal of molecular sciences · 2026-05-13

pmid:42196324

Mutant ATXN1 impacts human and mouse microglia and contributes to cognitive, mood, and motor deficits in SCA1 mice.

Adem,Selimovic, Gourango,Talukdar, Gavin,Fuchs, Vamika,Sharma, Khadija N,Abbas, Sriyan C,Reddy, Eshaan,Parnerkar, Ian M,Brooks, Ying,Zhang, Michael,Koob, Yasushi,Nakagawa, Harry,Orr, Marija,Cvetanovic

bioRxiv : the preprint server for biology · 2026-02-17

pmid:41727128

Valosin-Containing Protein as a therapeutic target in CAG repeat-driven Spinocerebellar ataxias: Integrative transcriptomic and computational insights.

Surbhi,Singh, Deepika,Joshi, Janki,Makani, Suchitra,Singh, Janhavi,Yadav, Shraddha,Chaurasiya, Chandmayee,Mohanty, Anand,Kumar, Royana,Singh

Computational biology and chemistry · 2025-12-11

pmid:41435767

The role of disease-associated short tandem repeats in amyotrophic lateral sclerosis.

Joke J F A,van Vugt, Ramona A J,Zwamborn, Egor,Dolzhenko, Michael A,Eberle, Ben,Weisburd, Erwin,Bekema, Maarten,Kooyman, Bi-Nan,Wang, Erik-Jan,Kamsteeg, Monique,Losekoot, Frank,Baas, Camilla,Novy, Helle,Høyer, Ruben P A,van Eijk, Michael A,van Es, Wouter,van Rheenen, Ammar,Al-Chalabi, Leonard H,van den Berg, Jan H,Veldink

Brain communications · 2025-12-09

pmid:41426430

Unbiased human genomic characterization of polyglutamine disorder genes to guide biological understanding and therapeutic strategies.

Kevin Lucy,Namuli, Britt I,Drögemöller, Galen E B,Wright

HGG advances · 2025-11-17

pmid:41254939

Genetic and Clinical Insights into ALS/FTD: Profiling a Rare Cohort to Explore Spectrum Heterogeneity.

Ana,Marjanovic, Elka,Stefanova, Vanja,Viric, Aleksa,Palibrk, Gorana,Mandić Stojmenović, Tanja,Stojković, Lenka,Stojadinovic, Ivana,Basta, Ivana,Novakovic, Zorica,Stević, Milena,Jankovic

Journal of personalized medicine · 2025-09-28

pmid:41149812

The Case of Spinocerebellar Ataxias in Amazonas (Northern Brazil): An Analysis of Disease Frequency from a Geographic, Historical, and Genetic-Evolutionary Perspective.

Diana Vieira,Brito, Marcus Vinicius,Della Coletta, Giselle Benevides Monteiro,Ferreira, Sabrina Rodrigues,da Silva, Patricia Batista de,Azevedo, Cleiton,Fantin

Cerebellum (London, England) · 2025-09-03

pmid:40900235

Diagnostic yield and limitations of whole-genome sequencing for hereditary cerebellar ataxia.

Wai Yan,Yau, Roisin,Sullivan, Emer,O'Connor, David,Pellerin, Michael H,Parkinson, Paola,Giunti, Marie-Josée,Dicaire, Matt C,Danzi, Stephan,Züchner, Bernard,Brais, Nicholas W,Wood, Henry,Houlden, Jana,Vandrovcova

Brain communications · 2025-05-17

pmid:40488180

Accurate Quantification of Mutant and Wild-Type polyQ Proteins Using Simple Western Capillary Immunoassays.

Bas,Röttgering, Janwillem,Testerink, Rudie,Weij, Chantal,Beekman, Nicole,Datson

Molecular neurobiology · 2025-05-31

pmid:40450087

Locus SCA1 ATXN1

Disease

Locus

Alleles

gnomAD

References

Additional Literature