Curation SCA12 PPP2R2B

Gene PPP2R2B

Disease SCA12

Inheritance AD

Score

7 + 1.5 = 8.5 / 18

Genetic + experimental = total

Classification

Moderate

Refuted

Moderate

Definitive

Last Updated 08/11/2025

Pubs Reviewed 3

Publication Span 24.58 years

Publication Interval 24.58 years

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.

All criTRia Curations Locus Page

Genetic evidence

Total: 7

Per page

Category	Type	Citation	Score	Details
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

Per page

Category	Type	Citation	Score	Details
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.

Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.