SCA8 ATXN8OS

Spinocerebellar ataxia type 8 (SCA8) is a subtype of type I autosomal dominant cerebellar ataxia (ADCA type I) characterized by cerebellar ataxia and cognitive dysfunction in almost three quarters of patients and pyramidal and sensory signs in approximately a third of patients¹.

Prevalence

0.5 100,000

<1/100,000²; expansion in 1:100-1200 chromosomes³. Found across ethnicities/ancestries, with population-dependent prevalence³.

Age of Onset Details

Typical: third to fifth decade (20-49); Range: 0³- 76⁴.

Locus

hg19

chr13:70713515-70713561

hg38

chr13:70139383-70139429

t2t

chr13:69361243-69361270

Details

Two genes span the CTG/CAG repeat and are expressed in opposite directions: ATXN8, a nearly pure polyglutamine repeat protein in the CAG direction, and ATXN8OS, which is transcribed to a noncoding CUG repeat RNA⁵. Reduced penetrance is found in alleles of all sizes, although penetrance appears higher at 71+ repeats and repeats at 50-70 appear less likely to result in disease^3,6. Roda et al. suggested that the ATXN8 or ATXN8OS gene should not be evaluated in isolation as a candidate gene for spinocerebellar degenerative disease⁷. CCG/CGG interruptions in high-penetrance SCA8 families increase RAN translation and protein toxicity⁸; Interruptions in CTG/CAG expansion by 1 or more CCG/CGG, CTA/TAG, CTC/GAG, CCA/TGG, or CTT/AAG trinucleotides have been observed in full-penetrance repeats^5,3.

Mechanism

GoF

Polyglutamine/toxic gain-of-function^9,3.

Year

1999¹⁰

Location in Gene

Coding Exon 1, or 3' UTR depending on transcript

Gene Strand

Alleles

Ref. Motif

CTG

Pathogenic (ref.)

CTG

Pathogenic (gene)

CTG

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:0012116

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

Spinocerebellar Ataxia Type 8

John Douglas,Cleary, S. H.,Subramony, Laura PW,Ranum

GeneReviews® · 1993-01-01

genereviews:NBK1268

A prospective trial comparing programmable targeted long-read sequencing and short-read genome sequencing for genetic diagnosis of cerebellar ataxia

Haloom,Rafehi, Liam G.,Fearnley, Justin,Read, Penny,Snell, Kayli C.,Davies, Liam,Scott, Greta,Gillies, Genevieve C.,Thompson, Tess A.,Field, Aleena,Eldo, Simon,Bodek, Ernest,Butler, Luke,Chen, John,Drago, Himanshu,Goel, Anna,Hackett, G. Michael,Halmagyi, Andrew,Hannaford, Katya,Kotschet, Kishore R.,Kumar, Smitha,Kumble, Matthew,Lee-Archer, Abhishek,Malhotra, Mark,Paine, Michael,Poon, Kate,Pope, Katrina,Reardon, Steven,Ring, Anne,Ronan, Matthew,Silsby, Renee,Smyth, Chloe,Stutterd, Mathew,Wallis, John,Waterston, Thomas,Wellings, Kirsty,West, Christine,Wools, Kathy H.C.,Wu, David J.,Szmulewicz, Martin B.,Delatycki, Melanie,Bahlo, Paul J.,Lockhart

Genome Research · 2025-02-27

doi:10.1101/gr.279634.124

Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8.

Melinda L,Moseley, Tao,Zu, Yoshio,Ikeda, Wangcai,Gao, Anne K,Mosemiller, Randy S,Daughters, Gang,Chen, Marcy R,Weatherspoon, H Brent,Clark, Timothy J,Ebner, John W,Day, Laura P W,Ranum

Nature genetics · 2006-06-25

pmid:16804541

RNA-mediated neurodegeneration in repeat expansion disorders.

Peter K,Todd, Henry L,Paulson

Annals of neurology · 2010-03-01

pmid:20373340

SCA8 should not be tested in isolation for ataxia.

Ricardo H,Roda, Alice B,Schindler, Craig,Blackstone

Neurology. Genetics · 2017-04-21

pmid:28451643

CCG•CGG interruptions in high-penetrance SCA8 families increase RAN translation and protein toxicity.

Barbara A,Perez, Hannah K,Shorrock, Monica,Banez-Coronel, Tao,Zu, Lisa El,Romano, Lauren A,Laboissonniere, Tammy,Reid, Yoshio,Ikeda, Kaalak,Reddy, Christopher M,Gomez, Thomas,Bird, Tetsuo,Ashizawa, Lawrence J,Schut, Alfredo,Brusco, J Andrew,Berglund, Lis F,Hasholt, Jorgen E,Nielsen, S H,Subramony, Laura Pw,Ranum

EMBO molecular medicine · 2021-10-11

pmid:34632710

omim:608768

An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8).

M D,Koob, M L,Moseley, L J,Schut, K A,Benzow, T D,Bird, J W,Day, L P,Ranum

Nature genetics · 1999-04-01

pmid:10192387

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

Cognitive-predominant spinocerebellar ataxia type 8 with posterior cingulate cortex hypoperfusion mimicking early-onset Alzheimer's disease: A case report.

Yuki,Nakagawa, Atsuhiko,Sugiyama, Shigeki,Hirano, Masahiro,Namiki, Satoshi,Kuwabara

Journal of Alzheimer's disease reports · 2025-10-08

pmid:41079917

Association of Non-Coding Repeat Expansions with Parkinson's Disease Risk: Evidence from a UK Biobank-Based Whole-Genome Sequencing Study.

Zhen,Hu, Qin-Qin,Yan, Jing-Jin,Wan, Yu,Fan, Jun,Liu

Movement disorders : official journal of the Movement Disorder Society · 2025-10-11

pmid:41074692

Spinocerebellar ataxias masquerading as movement disorders: clinical and genetic characterization.

Shanshan,Wei, Zhe,Zhao, Nan,Li, Xuan,Guo, Jiannan,Chen, Jing,Hu

Frontiers in neurology · 2025-09-10

pmid:41001200

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

Hemichorea as the sole clinical manifestation of spinocerebellar ataxia type 8: a case report.

Makoto,Kobayashi

BMC neurology · 2025-09-01

pmid:40890648

Whole genome sequencing analysis in primary lateral sclerosis (PLS) patients reveals mutations in neurological diseases-causing genes.

Arianna,Manini, Alberto,Brusati, Maurizio,Grassano, Giulia,Scacciatella, Silvia,Peverelli, Jacopo,Spagliardi, Viviana,Pensato, Alberto,Doretti, Rosario,Vasta, Umberto,Manera, Antonio,Canosa, Maura,Brunetti, Davide,Gentilini, Stefano,Messina, Federico,Verde, Cristina,Moglia, Claudia,Morelli, Eleonora,Dalla Bella, Pamela J,Keagle, John E,Landers, Cinzia,Gellera, Giuseppe,Lauria Pinter, Adriano,Chiò, Antonia,Ratti, Andrea,Calvo, Vincenzo,Silani, Nicola,Ticozzi

Journal of neurology · 2025-08-22

pmid:40844737

Non-coding repeat analyses in patients with Parkinson's disease.

Makito,Hirano, Makoto,Samukawa, Satoko,Miyatake, Yuko,Yamagishi, Chiharu,Isono, Rino,Yoshikawa, Kazumasa,Saigoh, Atsushi,Terayama, Yuji,Higashimoto, Eriko,Koshimizu, Takeshi,Mizuguchi, Kanako,Fujii, Yoshiyuki,Mitsui, Naomichi,Matsumoto, Yoshitaka,Nagai

Frontiers in neurology · 2025-07-22

pmid:40765612

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