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

Typical: 26-50; Range: 8-62^3,4.

HPO Terms

HP:0000317 Facial myokymia HP:0000496 Abnormality of eye movement HP:0000708 Atypical behavior HP:0000716 Depression HP:0000726 Dementia HP:0000739 Anxiety HP:0000746 Delusion HP:0001251 Ataxia HP:0001260 Dysarthria HP:0001272 Cerebellar atrophy HP:0001288 Gait disturbance HP:0001300 Parkinsonism HP:0001310 Dysmetria HP:0001317 Abnormal cerebellum morphology HP:0001347 Hyperreflexia HP:0002059 Cerebral atrophy HP:0002067 Bradykinesia HP:0002073 Progressive cerebellar ataxia HP:0002075 Dysdiadochokinesis HP:0002080 Intention tremor HP:0002120 Cerebral cortical atrophy HP:0002174 Postural tremor HP:0002317 Unsteady gait HP:0002345 Action tremor HP:0002346 Head tremor HP:0002375 Hypokinesia HP:0002406 Limb dysmetria HP:0002530 Axial dystonia HP:0007010 Poor fine motor coordination HP:0007141 Sensorimotor neuropathy HP:0007256 Abnormal pyramidal sign HP:0030188 Tremor by anatomical site HP:0100543 Cognitive impairment

Association

Mendelian

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 51-78⁵; intermediate alleles are associated with reduced penetrance⁶.

Mechanism

GoF

Polyalanine gain of function associated with RAN translation⁷.

Detection

RP-PCR generally detects expansions, while PCR fragment analysis approximates allele size. Large expansions may require Southern blot confirmation^8,9.

Year

1999⁹

Location in Gene

5' UTR

Gene Strand

Alleles

Ref. Motif

CTG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CTG

Pathogen. (gene)

CAG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interrup. (gene)

–

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

3omim:604326

Abnormal Amyloidogenesis Identified in Plasma of Patients with Spinocerebellar Ataxia Type 12.

Rebecca,Banerjee, Swarnava,Sengupta, Jyoti,Rungta, Sabbir,Ansari, Sattwika,Banerjee, Bishmita,Biswas, Rakhi,Pal, Sumantra,Chattarji, Supriyo,Choudhury, Hrishikesh,Kumar

Cerebellum (London, England) · 2026-05-09

pmid:42105155

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

8pmid:35262663

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)

Detection of short tandem repeat expansions on a targeted neurological gene panel using STRipy improves the diagnostic rate for ataxias.

Carolin K,Scriba, Chiara,Folland, Michael,Black, Jessica,Baker, Daniel,Abromeit, Samantha,Saw, Mei-Ting,Chiew, Rebecca,Gooding, Nigel G,Laing, Mark R,Davis, Gianina,Ravenscroft

Brain communications · 2026-03-16

pmid:42038259

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

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

Locus SCA12 PPP2R2B

Disease

Locus

Alleles

gnomAD

References

Additional Literature