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

chr5:146258291-146258322

hg38

chr5:146878728-146878759

t2t

chr5:147414734-147414765

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

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)

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 · 2024-11-20

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

Role of Bβ1 overexpression in the pathogenesis of SCA12.

Chengqian,Zhou, Fan,Tang, Tao,Dong, Hans B,Liu, Leon,Deng, Russell L,Margolis, Pan P,Li

Movement disorders : official journal of the Movement Disorder Society · 2024-05-26

pmid:38798069

Molecular clues unveiling spinocerebellar ataxia type-12 pathogenesis.

Manish,Kumar, Shweta,Sahni, Vivekanand,A, Deepak,Kumar, Neetu,Kushwah, Divya,Goel, Himanshi,Kapoor, Achal K,Srivastava, Mohammed,Faruq

iScience · 2024-04-18

pmid:38711441

Early-onset familial essential tremor is associated with nucleotide expansions of spinocerebellar ataxia in China.

Zhilin,Zheng, Zeyu,Zhu, Jiali,Pu, Chen,Zhou, Lanxiao,Cao, Dayao,Lv, Jinyu,Lu, Gaohua,Zhao, Yanxing,Chen, Jun,Tian, Xinzhen,Yin, Baorong,Zhang, Yaping,Yan, Guohua,Zhao

Molecular biology reports · 2024-01-16

pmid:38227102

Copy Number Variant Analysis of Spinocerebellar Ataxia Genes in a Cohort of Dutch Patients With Cerebellar Ataxia.

Fatemeh,Ghorbani, Eddy N,de Boer, Marloes,Benjamins-Stok, Corien C,Verschuuren-Bemelmans, Jurjen,Knapper, Jelkje,de Boer-Bergsma, Jeroen J,de Vries, Birgit,Sikkema-Raddatz, Dineke S,Verbeek, Helga,Westers, Cleo C,van Diemen

Neurology. Genetics · 2023-02-02

pmid:38058854

Clinical, Radiological, and Genetic Profile of Spinocerebellar Ataxia 12: A Hospital-Based Cohort Analysis.

Valakunja Harikrishna,Ganaraja, Vikram V,Holla, Albert,Stezin, Nitish,Kamble, Ravi,Yadav, Meera,Purushottam, Sanjeev,Jain, Pramod Kumar,Pal

Tremor and other hyperkinetic movements (New York, N.Y.) · 2022-04-21

pmid:35531119

Frequency of spinocerebellar ataxia mutations in patients with multiple system atrophy.

Anna I,Wernick, Ronald L,Walton, Alexandra I,Soto-Beasley, Shunsuke,Koga, Michael G,Heckman, Rebecca R,Valentino, Lukasz M,Milanowski, Dorota,Hoffman-Zacharska, Dariusz,Koziorowski, Anhar,Hassan, Ryan J,Uitti, William P,Cheshire, Wolfgang,Singer, Zbigniew K,Wszolek, Dennis W,Dickson, Phillip A,Low, Owen A,Ross

Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2021-01-27

pmid:33502644