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)

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

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

PolyQ-Expansion of Ataxin-2 Disrupts Microtubule Stability and Impairs Axon Outgrowth.

Sun K,Kim, Vladimir I,Gelfand

The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025-10-01

pmid:40908144

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

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

Influence of ATXN2 intermediate CAG repeats, 9bp duplication and alternative splicing on SCA3 pathogenesis.

Marilena,Lauerer, Jennifer,Faber, Nicolas,Casadei, Magda M,Santana, Georg,Auburger, Michaela,Pogoda, Jakob,Admard, Lea,Kaupp, Patricia Laura,Kos, Mafalda,Raposo, Manuela,Lima, Luis Pereira,de Almeida, Hector,Garcia-Moreno, Paola,Giunti, Jeroen,de Vries, Bart P,van de Warrenburg, Judith,van Gaalen, Marcus,Grobe-Einsler, Berkan,Koyak, Kathrin,Reetz, Friedrich,Erdlenbruch, Heike,Jacobi, Jon,Infante, Holger,Hengel, Ludger,Schöls, Thomas,Klockgether, Olaf,Rieß, Jeannette,Hübener-Schmid

Acta neuropathologica communications · 2025-07-19

pmid:40684213

Establishment of a humanized SCA2 mouse model carrying a CAA disruption preventing CAG repeat expansion in pathogenic genes.

Yao,Zhang, Yufei,Li, Lin,Zhang, Zhaoqing,Li, Keqin,Lin, Kai,Huang, Zhaoqing,Yang, Shaohui,Ma, Hao,Sun, Xiaochao,Zhang

Animal models and experimental medicine · 2025-06-24

pmid:40556342

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