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.

Prevalence

2.65 100,000

13-15% of global SCA prevalence, estimated to be 0.02-31/100,000^2,3: resultant estimate is 0.3-5/100,000. Found across ethnicities/ancestries, with population-dependent prevalence².

Age of Onset Details

Typical: 43-52²; Range: 16⁴- 73².

Locus

hg19

chr19:13318672-13318712

hg38

chr19:13207858-13207898

t2t

chr19:13333136-13333176

Details

The intermediate range (19-20 motifs)^5,2can be associated with a premutation, reduced penetrance, atypical phenotype, or a disease state when homozygous². 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 allele⁵. For individuals with a longest allele of 19-20, the presence of a second allele of 19-20 likely increases the risk of developing SCA6⁵.

Mechanism

GoF/LoF

Polyglutamine expansions associated increased expression of altered product leading to impaired gene binding and transcription factor function as well as cellular toxicity².

Year

1997⁶

Location in Gene

Coding, Last Exon: 47 or 48

Gene Strand

Alleles

Ref. Motif

CTG

Pathogenic (ref.)

CTG

Pathogenic (gene)

AGC

gnomAD

Pathogenic Genotype (%): % of individuals predicted to be affected based on their genotype

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0008457

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)

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

Diagnosis of hereditary ataxias: a real-world single center experience.

Adriana,Meli, Vincenzo,Montano, Giovanni,Palermo, Antonella,Fogli, Anna,Rocchi, Annalisa Lo,Gerfo, Rossella,Maltomini, Ludovica,Cori, Antonio,Siniscalchi, Clara,Bernardini, Giulia,Cecchi, Gabriele,Siciliano, Roberto,Ceravolo, Maria Adelaide,Caligo, Michelangelo,Mancuso, Piervito,Lopriore

Journal of neurology · 2025-01-15

pmid:39812846