SCA6 CACNA1A

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. has proposed that this expansion may have effects on chronotype, differing by sex and menopausal status, as well as depresssion 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 Details

Typical: 43-52³; Range: 16⁵- 73³.

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.

Mechanism

GoF/LoF

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

Year

1997⁷

Location in Gene

Coding, Last Exon: 47 or 48

Gene Strand

Alleles

Ref. Motif

CTG

Pathogenic (ref.)

CTG

Pathogenic (gene)

AGC

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 <i>CACNA1A</i> for Spinocerebellar Ataxia Type 6

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

Neurology Genetics · 2025-04-01

doi:10.1212/NXG.0000000000200245

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)

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

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

GAA-FGF14 Expansions and CACNA1A Variants: Phenotypic Overlap and Diagnostic Implications.

Elisabetta,Indelicato, Zofia,Fleszar, David,Pellerin, Wolfgang,Nachbauer, Stephan,Zuchner, Andreas,Traschütz, Matthias,Amprosi, Ludger,Schöls, Tobias B,Haack, Bernard,Brais, Sylvia,Boesch, Matthis,Synofzik

Movement disorders : official journal of the Movement Disorder Society · 2025-08-19

pmid:40879304

Comprehensive identification of pathogenic tandem repeat expansions in sporadic amyotrophic lateral sclerosis: advantages of long-read vs. short-read sequencing.

Eleonora,Sabetta, Karin,Rallmann, Jonas,Bergquist, Pille,Taba, Abigail L,Pfaff, Bal Hari,Poudel, Davide,Ferrari, Massimo,Locatelli, Sulev,Kõks

Experimental biology and medicine (Maywood, N.J.) · 2025-07-17

pmid:40746751

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

Homozygous CAG Repeat Expansion in Spinocerebellar Ataxia Type 6: Longitudinal Analysis of Vestibulo-Ocular Reflex Findings.

Jae-Myung,Kim, Tai-Seung,Nam, Jae-Hwan,Choi, Seung-Han,Lee

Cerebellum (London, England) · 2025-04-07

pmid:40189664