SCA12_PPP2R2B
- Gene
- PPP2R2B
- Disease
- SCA12
- Inheritance
- AD
- Classification
- Moderate
- Total Score
- 8.5
- Publications Reviewed
- 3
- Publication Span
- 24.58 years
- Last Updated
- 08/11/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt
Description
Spinocerebellar ataxia 12 (SCA12) is an autosomal dominant repeat expansion disorder associated with a CAG repeat expansion in the 5′ region/promoter of PPP2R2B. Reported families support segregation of expanded alleles with an adult-onset phenotype that often begins with coarse action tremor of the hands/head and later develops cerebellar ataxia; incomplete/age-dependent penetrance has been reported. The locus is rare globally but enriched in a northern Indian founder population. PPP2R2B encodes the brain-enriched PP2A-PR55β regulatory subunit; the pathogenic mechanism is still incompletely established, with proposed regulatory effects and possible gain-of-function/RAN-translation mechanisms.
Genetic evidence
Total: 7
| Singular Evidence | Probands | PMID:34711523 | 6 | SCA12 is described as relatively frequent in a northern Indian endogamous community due to a founder effect, caused by PPP2R2B repeat expansion, rare outside India, and characterized initially by coarse action tremor with later cerebellar signs. |
| Collective Evidence | Allele | PMID:38467784 | 1 | PPP2R2B SCA12 is listed as an autosomal dominant promoter CAG repeat expansion disorder with proposed gain-of-function/polyalanine and RAN-translation mechanisms; this is locus-specific but not primary allele-size correlation data. |
Experimental evidence
Total: 1.5
| Function | Biochemical function | PMID:10581021 | 0.5 | Gene-level evidence: PPP2R2B encodes brain-specific PP2A-PR55β, a regulatory subunit of protein phosphatase PP2A; PP2A is implicated in cell-cycle progression, tau phosphorylation, and apoptosis. Not SCA12-repeat-specific functional proof. |
| Function | Protein interaction | PMID:10581021 | 0.5 | Gene-level evidence: PR55β/PPP2R2B is described as a regulatory subunit of the trimeric PP2A holoenzyme. This supports pathway context but is not a direct SCA12 repeat-expansion protein-interaction assay. |
| Function | Regulatory impact | PMID:10581021 | 0.5 | Locus-specific regulatory context: the SCA12 CAG repeat lies in the 5′ region/putative 5′ UTR near PPP2R2B transcription-start and promoter elements; patient lymphoblastoid cells had no detectable PPP2R2B RNA or protein, so direct regulatory impact was not demonstrated in disease-relevant tissue. |
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.