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

–

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 analysis [@pmid:35573049].

Year

1997⁸

Location in Gene

Coding, Last Exon: 47 or 48

Gene Strand

Alleles

Ref. Motif

CTG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CTG

Pathogenic (gene)

AGC

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interruption (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

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)

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

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

Nature · 2026-04-08

pmid:41951733

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

Non-Huntington's disease chorea: an expanding universe with acquired causes.

Francisco,Cardoso, Débora,Maia, Ricardo,Maciel, Jonathan,Carr, Taku,Hatano, Alexandra,Durr, Werner,Poewe

Brain : a journal of neurology · 2026-01-30

pmid:41612618

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

Cerebellum (London, England) · 2025-09-04

pmid:40906330

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

Locus SCA6 CACNA1A

Disease

Locus

Alleles

gnomAD

References

Additional Literature