Spinocerebellar ataxia type 12

disease

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Also known as SCA12spinocerebellar ataxia 12

Summary

Spinocerebellar ataxia type 12 (MONDO:0011439) is a disease caused by PPP2R2B (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
Causal gene: PPP2R2B (GenCC Strong)
Cohort genes: 1
ClinVar variants: 6
Phenotypes (HPO): 21
Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		40	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0001251	Ataxia	Frequent (30-79%)
HP:0001272	Cerebellar atrophy	Frequent (30-79%)
HP:0001300	Parkinsonism	Frequent (30-79%)
HP:0001317	Abnormal cerebellum morphology	Frequent (30-79%)
HP:0001347	Hyperreflexia	Frequent (30-79%)
HP:0002059	Cerebral atrophy	Frequent (30-79%)
HP:0002345	Action tremor	Frequent (30-79%)
HP:0002406	Limb dysmetria	Frequent (30-79%)
HP:0030188	Tremor by anatomical site	Frequent (30-79%)
HP:0000708	Atypical behavior	Occasional (5-29%)
HP:0000726	Dementia	Occasional (5-29%)
HP:0001288	Gait disturbance	Occasional (5-29%)
HP:0002067	Bradykinesia	Occasional (5-29%)
HP:0002080	Intention tremor	Occasional (5-29%)
HP:0002174	Postural tremor	Occasional (5-29%)
HP:0002317	Unsteady gait	Occasional (5-29%)
HP:0002375	Hypokinesia	Occasional (5-29%)
HP:0007010	Poor fine motor coordination	Occasional (5-29%)
HP:0007141	Sensorimotor neuropathy	Occasional (5-29%)
HP:0007256	Abnormal pyramidal sign	Occasional (5-29%)
HP:0100543	Cognitive impairment	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia type 12
Mondo ID	MONDO:0011439
MeSH	C565790
OMIM	604326
Orphanet	98762
DOID	DOID:0050962
ICD-11	1210063722
NCIT	C154316
SNOMED CT	719208005
UMLS	C1858501
MedGen	347653
GARD	0010476
Is cancer (heuristic)	no

Also known as: SCA12 · spinocerebellar ataxia 12 · spinocerebellar ataxia type 12

Data availability: 6 ClinVar variants · 3 GenCC gene-disease records · 5 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant cerebellar ataxia › autosomal dominant cerebellar ataxia type I › spinocerebellar ataxia type 12

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

6 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 1 benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
624067	NM_181675.4(PPP2R2B):c.707A>G (p.Asn236Ser)	PPP2R2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1712310	NM_181675.4(PPP2R2B):c.737C>A (p.Thr246Lys)	PPP2R2B	Uncertain significance	criteria provided, single submitter
3780484	NM_181675.4(PPP2R2B):c.37_57dup (p.Ser19_Tyr20insSerPheLeuArgAspHisSer)	PPP2R2B	Uncertain significance	criteria provided, single submitter
3780485	NM_181675.4(PPP2R2B):c.41_58del (p.Phe14_Ser19del)	PPP2R2B	Uncertain significance	criteria provided, single submitter
548555	NM_181675.4(PPP2R2B):c.119C>T (p.Ala40Val)	PPP2R2B	Uncertain significance	criteria provided, single submitter
5614	NM_181675.3(PPP2R2B):c.27CAG[(7_28)[ (p.Ser10[(7-28)])	LOC108660405	Benign	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PPP2R2B	Strong	Autosomal dominant	spinocerebellar ataxia type 12	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PPP2R2B	Orphanet:98762	Spinocerebellar ataxia type 12

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PPP2R2B	HGNC:9305	ENSG00000156475	Q00005	Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PPP2R2B	Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform	The B regulatory subunit might modulate substrate selectivity and catalytic activity, and might also direct the localization of the catalytic enzyme to a particular subcellular compartment.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PPP2R2B	Scaffold/PPI	no		PP2A_PR55, WD40_rpt, WD40/YVTN_repeat-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
ganglionic eminence	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PPP2R2B	244	broad	marker	sperm, cortical plate, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PPP2R2B	2,948

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PPP2R2B	Q00005	90.37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
apoptotic process	1	28.7×	0.035	PPP2R2B

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PPP2R2B	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PPP2R2B

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PPP2R2B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

Cohort genes: PPP2R2B