SCA2 ATXN2

A subtype of type I autosomal dominant cerebellar ataxia (ADCA type I) characterized by truncal ataxia, dysarthria, slowed saccades and less commonly ophthalmoparesis and chorea¹.

Prevalence

1.5 100,000

1-2/100,000 (population-dependent)². Cases have been found across ethnicities/ancestries, with population-dependent prevalence³.

Age of Onset Details

Typical: 30-39³; Range: 2-86⁴.

Locus

hg19

chr12:112036753-112036823

hg38

chr12:111598949-111599019

t2t

chr12:111575873-111575940

Details

Full penetrance of single alleles occurs at ~35 repeats^3,5and pathogenic expansions have been documented as large as 500 repeats⁶. 33-34 length repeats are associated with reduced penetrance and later onset (age >50 years)³. Homozygous 31 repeat alleles may lead to recessive disease⁷, while a single 30-32 repeat is associated with increased ALS risk^3,8. There is some evidence that all CAG-repeat expansions in ATXN2 may be a risk factor for ALS, regardless of length and interruptions⁹. Interruptions observed include CAA, CGG, CGC, which appear to stabilize the allele in transmission³. May confer risk for amyotrophic lateral sclerosis¹⁰.

Mechanism

GoF/LoF

Polyglutamine cytoplasmic aggregates leading to cellular apoptosis; RAN translation implicated³.

Year

1996¹¹

Location in Gene

Coding Exon 1

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:0008458

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 2

Stefan M.,Pulst

GeneReviews® · 1993-01-01

genereviews:NBK1275

omim:183090

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

Childhood-onset ataxia: testing for large CAG-repeats in SCA2 and SCA7.

Rong,Mao, Arthur S,Aylsworth, Nicholas,Potter, William G,Wilson, Galen,Breningstall, Myra J,Wick, Dusica,Babovic-Vuksanovic, Martha,Nance, Marc C,Patterson, Christopher M,Gomez, Karen,Snow

American journal of medical genetics · 2002-07-15

pmid:12116207

Homozygous 31 trinucleotide repeats in the SCA2 allele are pathogenic for cerebellar ataxia.

Maya,Tojima, Gaku,Murakami, Rie,Hikawa, Hodaka,Yamakado, Hirofumi,Yamashita, Ryosuke,Takahashi, Masaru,Matsui

Neurology. Genetics · 2018-10-16

pmid:30533529

Amyotrophic lateral sclerosis risk for spinocerebellar ataxia type 2 ATXN2 CAG repeat alleles: a meta-analysis.

Annalese G,Neuenschwander, Khanh K,Thai, Karla P,Figueroa, Stefan M,Pulst

JAMA neurology · 2014-12-01

pmid:25285812

An observational study of pleiotropy and penetrance of amyotrophic lateral sclerosis associated with CAG-repeat expansion of ATXN2.

Koen C,Demaegd, Aoife,Kernan, Johnathan,Cooper-Knock, Joke J F A,van Vugt, Calum,Harvey, Tobias,Moll, David,O'Brien, Sarah,Gornall, Luke,Drury, Sali M K,Farhan, Patrick A,Dion, Guy A,Rouleau, Andrea,Western, Paul J,Parsons, Benjamin,Mclean, Michael,Benatar, Leonard H,van den Berg, Philip,Van Damme, Jan,Willem Dankbaar, Jeroen,Hendrikse, Wouter,Koole, Charlotte,de Bie, Esther,Hobson, Jan H,Veldink, Bart,van de Warrenburg, R Jeroen,Pasterkamp, Wouter,van Rheenen, Janine,Kirby, Pamela J,Shaw, Michael A,van Es

European journal of human genetics : EJHG · 2025-02-16

pmid:39956874

Gijs H P,Tazelaar, Steven,Boeynaems, Mathias,De Decker, Joke J F A,van Vugt, Lindy,Kool, H Stephan,Goedee, Russell L,McLaughlin, William,Sproviero, Alfredo,Iacoangeli, Matthieu,Moisse, Maarten,Jacquemyn, Dirk,Daelemans, Annelot M,Dekker, Rick A,van der Spek, Henk-Jan,Westeneng, Kevin P,Kenna, Abdelilah,Assialioui, Nica,Da Silva, Mónica,Povedano, Jesus S Mora,Pardina, Orla,Hardiman, François,Salachas, Stéphanie,Millecamps, Patrick,Vourc'h, Philippe,Corcia, Philippe,Couratier, Karen E,Morrison, Pamela J,Shaw, Christopher E,Shaw, R Jeroen,Pasterkamp, John E,Landers, Ludo,Van Den Bosch, Wim,Robberecht, Ammar,Al-Chalabi, Leonard H,van den Berg, Philip,Van Damme, Jan H,Veldink, Michael A,van Es

Brain communications · 2020-05-19

pmid:32954321

Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT.

K,Sanpei, H,Takano, S,Igarashi, T,Sato, M,Oyake, H,Sasaki, A,Wakisaka, K,Tashiro, Y,Ishida, T,Ikeuchi, R,Koide, M,Saito, A,Sato, T,Tanaka, S,Hanyu, Y,Takiyama, M,Nishizawa, N,Shimizu, Y,Nomura, M,Segawa, K,Iwabuchi, I,Eguchi, H,Tanaka, H,Takahashi, S,Tsuji

Nature genetics · 1996-11-01

pmid:8896556

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)

Valosin-Containing Protein as a therapeutic target in CAG repeat-driven Spinocerebellar ataxias: Integrative transcriptomic and computational insights.

Surbhi,Singh, Deepika,Joshi, Janki,Makani, Suchitra,Singh, Janhavi,Yadav, Shraddha,Chaurasiya, Chandmayee,Mohanty, Anand,Kumar, Royana,Singh

Computational biology and chemistry · 2025-12-11

pmid:41435767

The role of disease-associated short tandem repeats in amyotrophic lateral sclerosis.

Joke J F A,van Vugt, Ramona A J,Zwamborn, Egor,Dolzhenko, Michael A,Eberle, Ben,Weisburd, Erwin,Bekema, Maarten,Kooyman, Bi-Nan,Wang, Erik-Jan,Kamsteeg, Monique,Losekoot, Frank,Baas, Camilla,Novy, Helle,Høyer, Ruben P A,van Eijk, Michael A,van Es, Wouter,van Rheenen, Ammar,Al-Chalabi, Leonard H,van den Berg, Jan H,Veldink

Brain communications · 2025-12-09

pmid:41426430

PolyQ Expansion Controls Biomolecular Condensation and Aggregation of the N-Terminal Fragments of Ataxin-2.

Yin-Hu,Liu, Heng-Tong,Duan, Lei-Lei,Jiang, Hong-Yu,Hu

International journal of molecular sciences · 2025-11-28

pmid:41373690

Novel and rare variants in amyotrophic lateral sclerosis genes identified in Malaysian patients.

Nurul Angelyn,Zulhairy-Liong, Suzanna,Edgar, Melina,Ellis, Danqing,Zhu, Kaitao,Lai, David Paul,Capelle, Sakinah,Sabirin, Eu Way,Pek, Prasana,Nair, Chui Munn,Ang, Marina L,Kennerson, Nortina,Shahrizaila, Azlina,Ahmad-Annuar

Amyotrophic lateral sclerosis & frontotemporal degeneration · 2025-12-08

pmid:41359433

Identification of expanded and interrupted ATXN2 repeat expansions in Parkinson's disease and Lewy Body Dementia cohorts.

Longfei,Wang, Michael,Milton, Liam G,Fearnley, Oneil G,Bhalala, Melanie,Bahlo, Haloom,Rafehi

NPJ Parkinson's disease · 2025-11-27

pmid:41310328

Multiomics approach identifies SERPINB1 as candidate biomarker for spinocerebellar ataxia type 2.

Luis E,Almaguer-Mederos, Jana,Key, Nesli-Ece,Sen, Julia,Canet-Pons, Claudia,Döring, David,Meierhofer, Suzana,Gispert-Sánchez, Dany,Cuello-Almarales, Dennis,Almaguer-Gotay, Lidia M,Osorio-González, Raúl,Aguilera-Rodríguez, Jacqueline,Medrano-Montero, Georg,Auburger

Scientific reports · 2025-11-26

pmid:41298695

Unraveling the genetic landscape of ALS in Greece: identification of known and novel causative variants in a 353-patient cohort.

Chrisoula,Kartanou, Zoi,Kontogeorgiou, Theodoros,Loupis, Dimitrios M,Vrachnos, Nikolaos,Ragazos, Ifigenia,Spyropoulou, Maria,Petraki, Chrysoula,Koniari, Stavroula,Aristeidou, Eleftheria,Koropouli, Ariadne,Daponte, Michail,Rentzos, Elisabeth,Kapaki, Marios,Panas, Periklis,Makrythanasis, Leonidas,Stefanis, Georgios,Koutsis, Georgia,Karadima

Amyotrophic lateral sclerosis & frontotemporal degeneration · 2025-11-06

pmid:41196070

Genetic and Clinical Insights into ALS/FTD: Profiling a Rare Cohort to Explore Spectrum Heterogeneity.

Ana,Marjanovic, Elka,Stefanova, Vanja,Viric, Aleksa,Palibrk, Gorana,Mandić Stojmenović, Tanja,Stojković, Lenka,Stojadinovic, Ivana,Basta, Ivana,Novakovic, Zorica,Stević, Milena,Jankovic

Journal of personalized medicine · 2025-09-28

pmid:41149812

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