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

chr19:13318673-13318712

hg38

chr19:13207859-13207898

t2t

chr19:13333137-13333176

Details

The intermediate range (19 motifs)^5,2can be associated with a premutation, reduced penetrance, atypical phenotype, or a disease state when homozygous².

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

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

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

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

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)

Screening for SCA27B, CANVAS and other repeat expansion disorders in Greek patients with late-onset cerebellar ataxia suggests a need to update current diagnostic algorithms.

Georgios,Koutsis, Chrisoula,Kartanou, Zoi,Kontogeorgiou, Chrysoula,Koniari, Alexandros,Mitrousias, David,Pellerin, Marie-Jose,Dicaire, Pablo,Iruzubieta, Matt C,Danzi, Konstantinos,Athanassopoulos, Nikolaos,Ragazos, Maria,Stamelou, Michail,Rentzos, Evangelos,Anagnostou, Stephan,Zuchner, Bernard,Brais, Henry,Houlden, Marios,Panas, Leonidas,Stefanis, Georgia,Karadima

Journal of the neurological sciences · 2024-11-15

pmid:39571249

Genetic profiles of multiple system atrophy revealed by exome sequencing, long-read sequencing and spinocerebellar ataxia repeat expansion analysis.

Xu-Ying,Li, Hong,Lai, Xian,Li, Fanxi,Xu, Yang,Song, Zhanjun,Wang, Qibin,Li, Ruichai,Lin, Zhiheng,Xu, Chaodong,Wang

European journal of neurology · 2024-08-17

pmid:39152783

Spinocerebellar Ataxias: Phenotypic Spectrum of PolyQ versus Non-Repeat Expansion Forms.

João,Moura, Jorge,Oliveira, Mariana,Santos, Sara,Costa, Lénia,Silva, Carolina,Lemos, José,Barros, Jorge,Sequeiros, Joana,Damásio

Cerebellum (London, England) · 2024-07-24

pmid:39048885

Tremor-associated short tandem repeat intermediate and pathogenic expansions in familial essential tremor.

Xun,Zhou, Runcheng,He, Sheng,Zeng, Mingqiang,Li, Hongxu,Pan, Yuwen,Zhao, Zhenhua,Liu, Qian,Xu, Jifeng,Guo, Xinxiang,Yan, Jinchen,Li, Beisha,Tang, Qiying,Sun

Brain communications · 2024-06-29

pmid:38961870

Early-onset familial essential tremor is associated with nucleotide expansions of spinocerebellar ataxia in China.

Zhilin,Zheng, Zeyu,Zhu, Jiali,Pu, Chen,Zhou, Lanxiao,Cao, Dayao,Lv, Jinyu,Lu, Gaohua,Zhao, Yanxing,Chen, Jun,Tian, Xinzhen,Yin, Baorong,Zhang, Yaping,Yan, Guohua,Zhao

Molecular biology reports · 2024-01-16

pmid:38227102

The Cerebellar Cognitive Affective/Schmahmann Syndrome Scale in Spinocerebellar Ataxias.

Louisa P,Selvadurai, Susan L,Perlman, Tetsuo,Ashizawa, George R,Wilmot, Chiadi U,Onyike, Liana S,Rosenthal, Vikram G,Shakkottai, Henry L,Paulson, Sub H,Subramony, Khalaf O,Bushara, Sheng-Han,Kuo, Cameron,Dietiker, Michael D,Geschwind, Alexandra B,Nelson, Christopher M,Gomez, Puneet,Opal, Theresa A,Zesiewicz, Trevor,Hawkins, Talene A,Yacoubian, Peggy C,Nopoulos, Sharon J,Sha, Peter E,Morrison, Karla P,Figueroa, Stefan M,Pulst, Jeremy D,Schmahmann

Cerebellum (London, England) · 2024-01-02

pmid:38165578

Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis.

Yufen,Peng, Qi,Tu, Yao,Han, Liang,Gao, Chenyi,Wan

Open life sciences · 2023-12-12

pmid:38152578

Prevalence of repeat expansions causing autosomal dominant spinocerebellar ataxias in Hokkaido, the northernmost island of Japan.

Keiichi,Mizushima, Yuka,Shibata, Shinichi,Shirai, Masaaki,Matsushima, Satoko,Miyatake, Ikuko,Iwata, Hiroaki,Yaguchi, Naomichi,Matsumoto, Ichiro,Yabe

Journal of human genetics · 2023-10-17

pmid:37848721

Genome-wide identification of tandem repeats associated with splicing variation across 49 tissues in humans.

Kohei,Hamanaka, Daisuke,Yamauchi, Eriko,Koshimizu, Kei,Watase, Kaoru,Mogushi, Kinya,Ishikawa, Hidehiro,Mizusawa, Naomi,Tsuchida, Yuri,Uchiyama, Atsushi,Fujita, Kazuharu,Misawa, Takeshi,Mizuguchi, Satoko,Miyatake, Naomichi,Matsumoto

Genome research · 2023-03-27

pmid:37307504