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

HP:0000496 Abnormality of eye movement HP:0000514 Slow saccadic eye movements HP:0000543 Optic disc pallor HP:0000597 Ophthalmoparesis HP:0000623 Supranuclear ophthalmoplegia HP:0000639 Nystagmus HP:0000640 Gaze-evoked nystagmus HP:0000641 Dysmetric saccades HP:0000648 Optic atrophy HP:0001151 Impaired horizontal smooth pursuit HP:0001252 Hypotonia HP:0001257 Spasticity HP:0001260 Dysarthria HP:0001265 Hyporeflexia HP:0001272 Cerebellar atrophy HP:0001283 Bulbar palsy HP:0001284 Areflexia HP:0001288 Gait disturbance HP:0001290 Generalized hypotonia HP:0001310 Dysmetria HP:0001324 Muscle weakness HP:0001332 Dystonia HP:0001347 Hyperreflexia HP:0001350 Slurred speech HP:0002015 Dysphagia HP:0002067 Bradykinesia HP:0002070 Limb ataxia HP:0002071 Abnormality of extrapyramidal motor function HP:0002072 Chorea HP:0002073 Progressive cerebellar ataxia HP:0002075 Dysdiadochokinesis HP:0002078 Truncal ataxia HP:0002141 Gait imbalance HP:0002168 Scanning speech HP:0002174 Postural tremor HP:0002198 Dilated fourth ventricle HP:0002354 Memory impairment HP:0002363 Abnormal brainstem morphology HP:0002380 Fasciculations HP:0002460 Distal muscle weakness HP:0002483 Bulbar signs HP:0002495 Impaired vibratory sensation HP:0002503 Spinocerebellar tract degeneration HP:0002542 Olivopontocerebellar atrophy HP:0002839 Urinary bladder sphincter dysfunction HP:0002878 Respiratory failure HP:0003202 Skeletal muscle atrophy HP:0003394 Muscle spasm HP:0003401 Paresthesia HP:0003431 Decreased motor nerve conduction velocity HP:0003448 Decreased sensory nerve conduction velocity HP:0003487 Babinski sign HP:0003693 Distal amyotrophy HP:0003701 Proximal muscle weakness HP:0006801 Hyperactive deep tendon reflexes HP:0006937 Impaired distal tactile sensation HP:0007001 Loss of Purkinje cells in the cerebellar vermis HP:0007006 Dorsal column degeneration HP:0007078 Decreased amplitude of sensory action potentials HP:0007263 Spinocerebellar atrophy HP:0007328 Impaired pain sensation HP:0007338 Hypermetric saccades HP:0007366 Atrophy/Degeneration affecting the brainstem HP:0007377 Abnormality of somatosensory evoked potentials HP:0007928 Abnormal flash visual evoked potentials HP:0009830 Peripheral neuropathy HP:0010831 Impaired proprioception HP:0025331 Upgaze palsy HP:0025401 Staring gaze HP:0030216 Inertia HP:0040129 Abnormal nerve conduction velocity HP:0100543 Cognitive impairment HP:0410011 Abnormality of masticatory muscle

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 sizing². Standard fragment analysis does not resolve CAT interruptions, which require targeted analysis like RP-PCR or Sanger sequencing^10,2.

Year

1993¹¹

Location in Gene

Coding Exon 8

Gene Strand

Alleles

Ref. Motif

CTG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CTG

Pathogen. (gene)

CAG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

GAT, TTG

Interrup. (gene)

ATC, CAA

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

Detection Methods and Status of CAT Interruption of

Ja-Hyun,Jang, Sun Joo,Yoon, Sun-Kyung,Kim, Jin Whan,Cho, Jong-Won,Kim

Annals of laboratory medicine · 2022-03-01

pmid:34635619

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)

Repeat expansions in Parkinson's disease and parkinsonism across ancestries: insights from a global genetic cohort.

Lara M,Lange, Catalina,Cerquera-Cleves, Ai Huey,Tan, Shen-Yang,Lim, Njideka U,Okubadejo, Chin-Hsien,Lin, Pin-Shiuan,Chen, Jung Hwan,Shin, Azlina,Ahmad-Annuar, Laurel A,Screven, Viorica,Chelban, Allison A,Dilliot, André,Fienemann, Kamalini Ghosh,Galvelis, Henry,Houlden, Hirotaka,Iwaki, Zane,Jaunmuktane, Patrick W,Cullinane, Thomas,Warner, Johanna,Junker, Yuliia,Kanana, Ignacio J Keller,Sarmiento, Christine,Klein, Pin-Jui,Kung, Hampton L,Leonard, Niccoló E,Mencacci, Mike A,Nalls, Raquel,Real, Samia Ben,Sassi, Joanne,Trinh, Dan,Vitale, Ana,Westenberger, Lesley Y,Wu, Andrew B,Singleton, Huw R,Morris, Katja,Lohmann, Cornelis,Blauwendraat, Peter,Heutink, Zih-Hua,Fang

medRxiv : the preprint server for health sciences · 2026-06-22

pmid:42396269

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

Locus SCA1 ATXN1

Disease

Locus

Alleles

gnomAD

References

Additional Literature