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

HP:0000020 Urinary incontinence HP:0000510 Rod-cone dystrophy HP:0000514 Slow saccadic eye movements HP:0000597 Ophthalmoparesis HP:0000602 Ophthalmoplegia HP:0000623 Supranuclear ophthalmoplegia HP:0000639 Nystagmus HP:0000640 Gaze-evoked nystagmus HP:0000641 Dysmetric saccades HP:0000657 Oculomotor apraxia HP:0000726 Dementia HP:0001151 Impaired horizontal smooth pursuit HP:0001251 Ataxia HP:0001252 Hypotonia HP:0001257 Spasticity HP:0001260 Dysarthria HP:0001265 Hyporeflexia HP:0001272 Cerebellar atrophy HP:0001290 Generalized hypotonia HP:0001300 Parkinsonism HP:0001310 Dysmetria HP:0001332 Dystonia HP:0001336 Myoclonus HP:0002015 Dysphagia HP:0002063 Rigidity HP:0002066 Gait ataxia HP:0002067 Bradykinesia HP:0002070 Limb ataxia HP:0002072 Chorea HP:0002073 Progressive cerebellar ataxia HP:0002075 Dysdiadochokinesis HP:0002120 Cerebral cortical atrophy HP:0002172 Postural instability HP:0002174 Postural tremor HP:0002198 Dilated fourth ventricle HP:0002317 Unsteady gait HP:0002345 Action tremor HP:0002380 Fasciculations HP:0002495 Impaired vibratory sensation HP:0002503 Spinocerebellar tract degeneration HP:0002536 Abnormal cortical gyration HP:0002542 Olivopontocerebellar atrophy HP:0002839 Urinary bladder sphincter dysfunction HP:0003133 Abnormal spinocerebellar tract morphology HP:0003394 Muscle spasm HP:0003487 Babinski sign HP:0003693 Distal amyotrophy HP:0006801 Hyperactive deep tendon reflexes HP:0006955 Olivopontocerebellar hypoplasia HP:0008311 Spinal cord dorsal column hypomyelination HP:0012082 Cerebellar Purkinje layer atrophy HP:0012762 Cerebral white matter atrophy HP:0025461 Abnormal cell morphology HP:0030186 Kinetic tremor HP:0045007 Abnormal substantia nigra morphology

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 appear to stabilize the allele in transmission³. Among control alleles, two CAA interruptions are most common (~66%), followed by one (~33%), with three interruptions rare (<1%) across ancestry groups, though three CAA interruptions predominate among intermediate length alleles¹¹. CAG expansions in this locus also correlate with cognitive deficits in phonemic fluency, semantic fluency, and attentional matrices. Notably, attentional decline worsens with disease progression¹². Intermediate and expanded alleles also correlate with Parkinson's disease risk in a length-dependent manner, with ≥32 repeats associated with over four-fold increased risk in individuals of European ancestry, and the great majority of expanded alleles in this range carry CAA interruptions¹³.

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 repeats³.

Year

1996¹⁴

Location in Gene

Coding Exon 1

Gene Strand

Alleles

Ref. Motif

CTG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CTG

Pathogen. (gene)

CAG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

TTG

Interrup. (gene)

CAA

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

Dissecting the relationship between haplotypes around ATXN2 CAG repeats and the number of CAA interruptions by long-read sequencing.

Beoung Hun,Lee, Joe,Chan, Yuk Yee,Leung, Corey T,McMillan, Yuanquan,Song, Defne A,Amado, Kai,Wang

medRxiv : the preprint server for health sciences · 2026-07-22

pmid:42539086

Longitudinal study of cognitive and psychiatric functions in spinocerebellar ataxia types 1 and 2.

Roberto,Fancellu, Dominga,Paridi, Chiara,Tomasello, Marta,Panzeri, Anna,Castaldo, Silvia,Genitrini, Paola,Soliveri, Floriano,Girotti

Journal of neurology · 2013-12-01

pmid:24122064

Repeat expansions in Parkinson's disease and parkinsonism across ancestries: insights from a global genetic cohort.

Lara M,Lange, Catalina,Cerquera-Cleves, Ai Huey,Tan, Shen-Yang,Lim, Njideka U,Okubadejo, Chin-Hsien,Lin, Pin-Shiuan,Chen, Jung Hwan,Shin, Azlina,Ahmad-Annuar, Laurel A,Screven, Viorica,Chelban, Allison A,Dilliot, André,Fienemann, Kamalini Ghosh,Galvelis, Henry,Houlden, Hirotaka,Iwaki, Zane,Jaunmuktane, Patrick W,Cullinane, Thomas,Warner, Johanna,Junker, Yuliia,Kanana, Ignacio J Keller,Sarmiento, Christine,Klein, Pin-Jui,Kung, Hampton L,Leonard, Niccoló E,Mencacci, Mike A,Nalls, Raquel,Real, Samia Ben,Sassi, Joanne,Trinh, Dan,Vitale, Ana,Westenberger, Lesley Y,Wu, Andrew B,Singleton, Huw R,Morris, Katja,Lohmann, Cornelis,Blauwendraat, Peter,Heutink, Zih-Hua,Fang

medRxiv : the preprint server for health sciences · 2026-06-22

pmid:42396269

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)

Dissecting the relationship between haplotypes around ATXN2 CAG repeats and the number of CAA interruptions by long-read sequencing.

Beoung Hun,Lee, Joe,Chan, Yuk Yee,Leung, Corey T,McMillan, Yuanquan,Song, Defne A,Amado, Kai,Wang

medRxiv : the preprint server for health sciences · 2026-07-22

pmid:42539086

How Early Should I Refer My Patient? The Benefits of a Quick Ophthalmic Referral in Spinocerebellar Ataxias, a Case Series and Literature Review.

Andrea B,Fiscal-Carvajal, José L,De-León-Guerra, Cristian E,Salinas-Aguirre, Marisol,Ibarra-Ramírez, Marissa L,Fernández-de-Luna, Ingrid E,Estrada-Bellmann, Joel,Arenas-Estala, Luis D,Campos-Acevedo, Jibran,Mohamed-Noriega

Brain sciences · 2026-07-17

pmid:42512530

N140 Latency as a Novel Biomarker for the Evaluation of Somatosensory Dysfunction in Patients with Spinocerebellar Ataxia Type 2.

Joel,Gutiérrez, Rachel,Pérez-Lalana, Reidenis,Torres-Vega, Roberto,Rodríguez-Labrada, Bárbara A,Hernández, Mario,Fernández, Yaimee,Vázquez-Mojena, Norge,Santisteban-Velázquez, Zurina,Lestayo, Yamile,Garcia, Luis,Velázquez-Pérez

Cerebellum (London, England) · 2026-07-25

pmid:42501220

Repeat expansions in Parkinson's disease and parkinsonism across ancestries: insights from a global genetic cohort.

medRxiv : the preprint server for health sciences · 2026-06-22

pmid:42396269

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

Behavioral and Personality Changes as the First Manifestation of Spinocerebellar Ataxia Type 2.

Davide,Vilella, Daniele,Urso, Agnese,Valguarnera, Giuseppe,Volpe, Maria,Accadia, Chiara,Zecca, Alessandra,Vitulli, Roberto,De Blasi, Alessandro,Bertolino, Giancarlo,Logroscino

Cerebellum (London, England) · 2026-04-30

pmid:42060068

Locus SCA2 ATXN2

Disease

Locus

Alleles

gnomAD

References

Additional Literature