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

Typical: 30-39³; Range: 2-86⁴.

HPO Terms

–

Association

MendelianRiskModifier

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 29-32 repeat is associated with increased ALS risk^3,8,9. There is some evidence that all CAG-repeat expansions in ATXN2 may be a risk factor for ALS, regardless of length and interruptions¹⁰. CAA interruptions have been observed which appear to stabilize the allele in transmission³.

Mechanism

GoF/LoF

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

Detection

RP-PCR with fragment analysis is commonly used for detection, while Southern blotting is required to estimate size over 100 repeats [@genereviews:NBK1275].

Year

1996¹¹

Location in Gene

Coding Exon 1

Gene Strand

Alleles

Ref. Motif

CTG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CTG

Pathogenic (gene)

AGC

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

TTG

Interruption (gene)

AAC

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

4omim: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

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

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

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)

Genetic Variants and Clinical Characteristics of Young-Onset Parkinson's Disease in the Hakka Population of Western Fujian.

Li-Ying,Pan, Fang,Guo, Chong,Zheng, Xiao-Hong,Hu, Yan-Gui,Chen, Rong-Rong,Lin

Brain and behavior · 2026-06-01

pmid:42204920

Computational Short Tandem Repeat Genotyping Reveals Clinically Relevant Expansions in a Large Turkish Neurodegeneration Disease Cohort.

Zakhiriddin,Khojakulov, Robin J,Palvadeau, Müge,Kovancılar-Koç, Irmak,Atay, Irmak,Şahbaz, Şeyma,Tekgül, Ayça,Şahin, Esmer Zeynep Duru,Badakal, Tuğçe,Gül-Demirkale, Vildan,Çiftçi, Elif,Bayraktar, Ceren,Tunca, Natalia,Smolina, Fulya,Akçimen, Ayşe Nazlı,Başak

International journal of molecular sciences · 2026-05-13

pmid:42196324

Identification of FGF14 GAA Expansions in Polish Patients with Undiagnosed Cerebellar Ataxia - A Preliminary Study.

Marta,Matlawska, Karolina,Ziora-Jakutowicz, Marie-Josee,Dicaire, Joanna,Pera, David,Pellerin, Bernard,Brais, Pablo,Iruzubieta, Ewelina,Elert-Dobkowska, Anna,Sulek

Cerebellum (London, England) · 2026-05-07

pmid:42096001

Targeting the integrated stress response or Ataxin-2 alleviates neurodegeneration in PolyGR models of C9orf72 associated frontotemporal dementia and amyotrophic lateral sclerosis.

Nikki S,Harper, Joanne L,Sharpe, Jasmine,Speranza, Ravinder,Gulia, Jeffrey X,Chen, Scott P,Allen, Manpreet S,Atwal, Stuart,Pickering-Brown, Matthew R,Livesey, Craig L,Bennett, Andreas,Prokop, Albert R,La Spada, Ryan J H,West

Acta neuropathologica communications · 2026-05-05

pmid:42087256

Peripheral lymphocyte subsets in spinocerebellar Ataxia type 2: Insights into disease mechanisms and potential immunomodulation.

Yaimeé,Vázquez-Mojena, Roberto,Rodríguez-Labrada, Lisis,Martínez Martí, Irenia,Horruitiner Gutiérrez, Yanetsy,Córdova-Rodríguez, Rolando,Zamora-Fung, Mario E,Fernández-Herrera, Ricardo,Ortega Sanchez, Diana Iris,Zamora-Loyarte, Lilian,Leyva Medrano, Mabel,Feria Rodríguez, María de Los Angeles,Robinson-Agramonte, Nancy,Pavón-Fuentes, Luis,Velázquez-Pérez

Journal of neuroimmunology · 2026-04-19

pmid:42019185

The Role of D/H Isotope Exchange in Stabilizing Trinucleotide Repeat Expansions in the CAG Tract of the ATXN2 Gene.

A A,Dorohova, I M,Chernukha, L V,Fedulova, J L,Hernandez-Caceres, M I,Drobotenko, S S,Dzhimak

Doklady. Biochemistry and biophysics · 2026-03-30

pmid:41912844

Monitoring the Progression of Pre-Ataxic Gait in SCA2 with Inertial Sensors Over Four Years.

Luis,Velázquez-Pérez, Roberto,Rodríguez-Labrada, Yasmany,Gonzalez-Garcés, Frank J,Carrillo-Rodes, Julio C,Rodríguez-Díaz, Yaimeé,Vázquez-Mojena, Ulf,Ziemann, Georg,Auburger, Fay,Horak, Christopher,Gomez

Cerebellum (London, England) · 2026-03-25

pmid:41876820

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

Bi-allelic intermediate ATXN2 repeat expansions are associated with slow progressing, leg-onset familial ALS.

Koen Cedric,Demaegd, Wouter,Koole, Joke Jfa,van Vugt, Jan Willem,Dankbaar, Jeroen,Hendrikse, A,Nazlı Başak, Mamede,de Carvalho, Philippe,Corcia, Philippe,Codron, Emilien,Bernard, Claire,Guissart, Philippe,Couratier, Mónica,Povedano Panades, Pieter A,van Doorn, Bart P,Warrenburg, Johnathan,Cooper-Knock, R Jeroen,Pasterkamp, Wouter,van Rheenen, Philip,van Damme, Leonard H,van den Berg, Jan Herman,Veldink, Michael A,van Es

BMJ neurology open · 2026-02-18

pmid:41728197

Locus SCA2 ATXN2

Disease

Locus

Alleles

gnomAD

References

Additional Literature