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

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

HPO Terms

–

Association

Mendelian

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.

Detection

Short-read genome sequencing has been reported to underestimate expansion size [@pmid:40015980; @genereviews:NBK1268]. RP-PCR has detected large expansions while long-read sequencing and Southern blotting estimated size more accurately [@genereviews:NBK1268].

Year

1999¹⁰

Location in Gene

Coding Exon 1, or 3' UTR depending on transcript

Gene Strand

Alleles

Ref. Motif

CTG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CTG

Pathogenic (gene)

CTG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

CCG, CTA, CTC, CCA, CTT

Interruption (gene)

CCG, ACT, CCT, ACC, CTT

gnomAD

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 · 2025-04-14

pmid:40015980

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

9omim: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)

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

Generation of an induced pluripotent stem cell line (KCGMHi003-A) from a patient with spinocerebellar ataxia type 8 (SCA8).

Min-Yu,Lan, Sheng-Jye,Lim, Huai-En,Lu, Meng-Han,Tsai

Stem cell research · 2025-12-05

pmid:41353794

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

Locus SCA8 ATXN8OS

Disease

Locus

Alleles

gnomAD

References

Additional Literature