Spinocerebellar ataxia type 6 (SCA6) is the most common subtype of autosomal dominant cerebellar ataxia type III (ADCA type III) characterized by late-onset and slowly progressive gait ataxia and other cerebellar signs such as impaired muscle coordination and nystagmus¹. Ao et al. have proposed that this expansion may have effects on chronotype, differing by sex and menopausal status, as well as depression severity².

Prevalence

2.65 100,000

13-15% of global SCA prevalence, estimated to be 0.02-31/100,000^3,4: resultant estimate is 0.3-5/100,000. Found across ethnicities/ancestries, with population-dependent prevalence³.

Age of Onset

Typical: 43-52³; Range: 16⁵- 73³.

HPO Terms

HP:0000504 Abnormality of vision HP:0000639 Nystagmus HP:0000643 Blepharospasm HP:0000651 Diplopia HP:0000763 Sensory neuropathy HP:0001251 Ataxia HP:0001260 Dysarthria HP:0001272 Cerebellar atrophy HP:0001310 Dysmetria HP:0001332 Dystonia HP:0001347 Hyperreflexia HP:0001350 Slurred speech HP:0002015 Dysphagia HP:0002017 Nausea and vomiting HP:0002066 Gait ataxia HP:0002073 Progressive cerebellar ataxia HP:0002078 Truncal ataxia HP:0002080 Intention tremor HP:0002083 Migraine without aura HP:0002120 Cerebral cortical atrophy HP:0002172 Postural instability HP:0002311 Incoordination HP:0002317 Unsteady gait HP:0002321 Vertigo HP:0002359 Frequent falls HP:0002505 Loss of ambulation HP:0003487 Babinski sign HP:0007670 Abnormal vestibulo-ocular reflex HP:0007772 Impaired smooth pursuit HP:0007979 Gaze-evoked horizontal nystagmus HP:0010544 Vertical nystagmus HP:0030511 Bradyopsia HP:0030842 Choking episodes

Association

Mendelian

Locus

hg19 chr19:13318672-13318712

hg38 chr19:13207858-13207898

t2t chr19:13333136-13333176

Details

The intermediate range (19-20 motifs)^6,3can be associated with a premutation, reduced penetrance, atypical phenotype, or a disease state when homozygous³. When the longer allele is > 22 motifs, the short allele does not play a role in pathogenicity/age of onset, but expansions of 21-22 motifs have age of onset influenced by the smaller allele⁶. For individuals with a longest allele of 19-20, the presence of a second allele of 19-20 likely increases the risk of developing SCA6⁶. Undiagnosed carriers of pathogenic range repeats in CACNA1A exhibit significant cerebellar volume loss and elevated NEFL levels before clinical diagnosis, also seen in other loci⁷.

Mechanism

GoF/LoF

Polyglutamine expansions associated with increased expression of altered product leading to impaired gene binding and transcription factor function as well as cellular toxicity³.

Detection

Expansions have been detected by PCR fragment analysis⁸.

Year

1997⁹

Location in Gene

Coding, Last Exon: 47 or 48

Gene Strand

Alleles

Ref. Motif

CTG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CTG

Pathogen. (gene)

CAG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interrup. (gene)

–

gnomAD

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0008457

Sex- and Depression-specific Effects of Non-pathogenic CAG Repeats in

Linjun,Ao, Raymond,Noordam, N,Ahmad Aziz, Yuri,Milaneschi, Diana,van Heemst, Frits R,Rosendaal, Brenda W J H,Penninx, Ko Willems,van Dijk, Tamar,Sofer, Heming,Wang, Tariq,Faquih

medRxiv : the preprint server for health sciences · 2025-11-27

pmid:41358280

Spinocerebellar Ataxia Type 6

Hannah L.,Casey, Christopher M.,Gomez

GeneReviews® · 1993-01-01

genereviews:NBK1140

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

Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics.

Shinsuke,Fujioka, Christina,Sundal, Zbigniew K,Wszolek

Orphanet journal of rare diseases · 2013-01-18

pmid:23331413

Redefining the Pathogenic CAG Repeat Units Threshold in

Yuya,Hatano, Tomohiko,Ishihara, Sachiko,Hirokawa, Hidetoshi,Date, Yuji,Takahashi, Hidehiro,Mizusawa, Osamu,Onodera

Neurology. Genetics · 2025-02-21

pmid:39996131

Population-scale repeat expansions elucidate disease risk and brain atrophy.

Vijay Kumar,Pounraja, Jae Hoon,Sul, Joseph,Herman, Sean,O'Keeffe, Veera,Rajagopal, Xiaodong,Bai, Michael D,Kessler, Neelroop,Parikshak, Karl,Landheer, Xingmin,Zhang, Sean,Yu, Lance,Zhang, Michelle G,LeBlanc, Jennifer,Rico-Varela, Frederic,Grau, Sarah,Wolf, Sriramkumar,Sundaramoorthy, Farshid,Sepehrband, Eli A,Stahl, Yuda,Huo, Mohsin,Ahmed, Susan,Croll, William,Salerno, John D,Overton, Jonathan,Marchini, Jeffrey,Reid, Luca A,Lotta, Aris,Baras, Goncalo R,Abecasis, Giovanni,Coppola, Sahar,Gelfman

Nature · 2026-04-08

pmid:41951733

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

Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel.

O,Zhuchenko, J,Bailey, P,Bonnen, T,Ashizawa, D W,Stockton, C,Amos, W B,Dobyns, S H,Subramony, H Y,Zoghbi, C C,Lee

Nature genetics · 1997-01-01

pmid:8988170

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

Replication analysis of the PRKN V380L (rs1801582) variant in a Japanese cohort of spinocerebellar ataxia type 3.

Ekaterina,Nadbitova, Nobuyuki,Takei, Sachiko,Hirokawa, Yuya,Hatano, Tomohiko,Ishihara, Osamu,Onodera, Yuka Mitsuhashi,Koike

BMC neurology · 2026-06-23

pmid:42337487

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

Detection of short tandem repeat expansions on a targeted neurological gene panel using STRipy improves the diagnostic rate for ataxias.

Carolin K,Scriba, Chiara,Folland, Michael,Black, Jessica,Baker, Daniel,Abromeit, Samantha,Saw, Mei-Ting,Chiew, Rebecca,Gooding, Nigel G,Laing, Mark R,Davis, Gianina,Ravenscroft

Brain communications · 2026-03-16

pmid:42038259

Metformin improves RAN protein pathology, alternative splicing, and behavioral phenotypes in SCA8 mice.

Lisa El,Romano, Setsuki,Tsukagoshi, Emily E,Davey-Osuch, Ramadan,Ajredini, Kamat,Manasi, Tala Vr,Ortiz, Eduardo,Rijos, Nathan J,Bourgon, S Elaine,Ames, Timothy J,Garrett, John D,Cleary, Eric T,Wang, Laura Pw,Ranum

Life science alliance · 2026-03-02

pmid:41771688

Short tandem repeat expansions in patients with neurodegenerative dementia.

Yuan,Zhu, Xuewen,Xiao, Yiliang,Liu, Zheng,Wang, Tengfei,Luo, Tianyan,Xu, Qijie,Yang, Xiaoli,Hao, Cong,Zhang, Sizhe,Zhang, Shilin,Luo, Yafang,Zhou, Xinxin,Liao, Yun,Tian, Ling,Weng, Liangjuan,Fang, Beisha,Tang, Bin,Jiao, Jinchen,Li, Lu,Shen

EBioMedicine · 2026-02-26

pmid:41762523

The genetic landscape of spinocerebellar ataxias in Taiwan: Insights from 876 genetically confirmed cases.

Shih-Chun,Lan, Cheng-Tsung,Hsiao, Kang-Yang,Jih, Yi-Chu,Liao, Yi-Chung,Lee

Parkinsonism & related disorders · 2025-10-12

pmid:41082794

Repeat Variants, Biomarkers, and Molecular Signatures in Parkinson's Disease:

Jose Miguel,Laffita-Mesa, Martin,Paucar, Per,Svenningsson

International journal of molecular sciences · 2025-09-20

pmid:41009775

Ocular Motor and Vestibular Profile in Spinocerebellar Ataxia Type 27B: Toward a Practical Bedside Diagnostic Framework.

Leonardo Eleuterio,Ariello, Daniel R,Gold, Weiyi,Mu, Michael C,Schubert, Claire,Allen, Ashley,Paul, David P W,Rastall