SCA12 PPP2R2B

Spinocerebellar ataxia type 12 (SCA12) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I). It is characterized by the presence of action tremor associated with relatively mild cerebellar ataxia. Associated pyramidal and extrapyramidal signs and dementia have been reported¹.

Prevalence

Frequent in India; rare in other populations².

Age of Onset Details

Typical: 26-50; Range: 8-56³.

Locus

hg19

chr5:146258290-146258322

hg38

chr5:146878727-146878759

t2t

chr5:147414733-147414780

Details

Benign range is 6-32 repeats, intermediate range 40-49, and pathogenic range is 51-78⁴; intermediate alleles are associated with reduced penetrance⁵.

Mechanism

GoF

Polyalanine gain of function associated with RAN translation⁶.

Year

1999⁷

Location in Gene

5' UTR

Gene Strand

Alleles

Ref. Motif

GCT

Pathogenic (ref.)

GCT

Pathogenic (gene)

AGC

gnomAD

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0011439

Spinocerebellar ataxias in Asia: Prevalence, phenotypes and management.

Teije,van Prooije, Norlinah Mohamed,Ibrahim, Shahrul,Azmin, Bart,van de Warrenburg

Parkinsonism & related disorders · 2021-10-22

pmid:34711523

omim:604326

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

SCA12 is a rare locus for autosomal dominant cerebellar ataxia: a study of an Indian family.

H,Fujigasaki, I C,Verma, A,Camuzat, R L,Margolis, C,Zander, A S,Lebre, L,Jamot, R,Saxena, I,Anand, S E,Holmes, C A,Ross, A,Dürr, A,Brice

Annals of neurology · 2001-01-01

pmid:11198281

Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications.

Indhu-Shree,Rajan-Babu, Egor,Dolzhenko, Michael A,Eberle, Jan M,Friedman

Nature reviews. Genetics · 2024-03-11

pmid:38467784

Expansion of a novel CAG trinucleotide repeat in the 5' region of PPP2R2B is associated with SCA12.

S E,Holmes, E E,O'Hearn, M G,McInnis, D A,Gorelick-Feldman, J J,Kleiderlein, C,Callahan, N G,Kwak, R G,Ingersoll-Ashworth, M,Sherr, A J,Sumner, A H,Sharp, U,Ananth, W K,Seltzer, M A,Boss, A M,Vieria-Saecker, J T,Epplen, O,Riess, C A,Ross, R L,Margolis

Nature genetics · 1999-12-01

pmid:10581021

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)

Precision Diagnosis of Wilson Disease Using a MultiGene Panel: Insights From a Prospective Cohort Study.

Jie,Lin, You-Liang,Wang, Yongqiang,Qu, Senwei,Dong, Yaofeng,Fang, Rukai,Chen, Ying,Ding, Weihong,Lin, Jian,Chen, Naiqing,Cai, Ning,Wang, Wan-Jin,Chen, Yi,Lin, Zhiqiang,Wang

Neurology. Genetics · 2026-03-03

pmid:41788301

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

Mitochondrial quality control gene expression in peripheral blood mononuclear cells of SCA12 patients.

Sabbir,Ansari, Jyoti,Rungta, Rebecca,Banerjee, Swarnava,Sengupta, Bishmita,Biswas, Rakhi,Pal, Sanjit,Dey, Sumantra,Chattarji, Jacky,Ganguly, Supriyo,Choudhury, Hrishikesh,Kumar

Parkinsonism & related disorders · 2026-02-12

pmid:41691974

Non-Huntington's disease chorea: an expanding universe with acquired causes.

Francisco,Cardoso, Débora,Maia, Ricardo,Maciel, Jonathan,Carr, Taku,Hatano, Alexandra,Durr, Werner,Poewe

Brain : a journal of neurology · 2026-01-30

pmid:41612618

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

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

De novo missense variants in the PP2A regulatory subunit PPP2R2B in a neurodevelopmental syndrome: potential links to mitochondrial dynamics and spinocerebellar ataxias.

Priyanka,Sandal, Chian Ju,Jong, Ronald A,Merrill, Grace J,Kollman, Austin H,Paden, Eric G,Bend, Jennifer,Sullivan, Rebecca C,Spillmann, Vandana,Shashi, Anneke T,Vulto-van Silfhout, Rolph,Pfundt, Bert B A,de Vries, Pan P,Li, Louise S,Bicknell, Stefan,Strack

Human molecular genetics · 2025-01-29

pmid:39565297

Non-motor symptoms in patients with Spinocerebellar ataxia type 12.

Purba,Basu, Supriyo,Choudhury, Siddhartha Sankar,Mondal, Ummatul,Siddique, Simin,Rahman, Jacky,Ganguly, Soumava,Mukherjee, Nilam,Singh, Mona,Tiwari, Hrishikesh,Kumar

Frontiers in neurology · 2024-10-14

pmid:39469072

Tremor-associated short tandem repeat intermediate and pathogenic expansions in familial essential tremor.

Xun,Zhou, Runcheng,He, Sheng,Zeng, Mingqiang,Li, Hongxu,Pan, Yuwen,Zhao, Zhenhua,Liu, Qian,Xu, Jifeng,Guo, Xinxiang,Yan, Jinchen,Li, Beisha,Tang, Qiying,Sun

Brain communications · 2024-06-29

pmid:38961870