Spinocerebellar ataxia type 23

Summary

Spinocerebellar ataxia type 23 (MONDO:0012449) is a disease caused by PDYN (GenCC Strong), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PDYN (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 73
• Phenotypes (HPO): 10
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

10 HPO clinical features (Orphanet curated; top 10 by frequency):

HPO ID	Term	Frequency
HP:0001347	Hyperreflexia	Very frequent (80-99%)
HP:0002066	Gait ataxia	Very frequent (80-99%)
HP:0002070	Limb ataxia	Very frequent (80-99%)
HP:0002073	Progressive cerebellar ataxia	Very frequent (80-99%)
HP:0000514	Slow saccadic eye movements	Frequent (30-79%)
HP:0001260	Dysarthria	Frequent (30-79%)
HP:0001310	Dysmetria	Frequent (30-79%)
HP:0003487	Babinski sign	Frequent (30-79%)
HP:0006886	Impaired distal vibration sensation	Frequent (30-79%)
HP:0010831	Impaired proprioception	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia type 23
Mondo ID	MONDO:0012449
MeSH	C537201
OMIM	610245
Orphanet	101108
DOID	DOID:0050973
ICD-11	1340267869
SNOMED CT	718772002
UMLS	C1853250
MedGen	339942
GARD	0009950
Is cancer (heuristic)	no

Also known as: SCA23 · spinocerebellar ataxia 23 · spinocerebellar ataxia type 23

Data availability: 73 ClinVar variants · 3 GenCC gene-disease records.

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 23

Related subtypes (29): Machado-Joseph disease, spinocerebellar ataxia type 29, spinocerebellar ataxia type 34, spinocerebellar ataxia type 1, spinocerebellar ataxia type 2, spinocerebellar ataxia type 4, cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome, autosomal dominant cerebellar ataxia, deafness and narcolepsy, spinocerebellar ataxia type 12, spinocerebellar ataxia type 13, spinocerebellar ataxia type 14, spinocerebellar ataxia type 15/16, spinocerebellar ataxia type 17, spinocerebellar ataxia type 19/22, spinocerebellar ataxia type 21, spinocerebellar ataxia type 18, spinocerebellar ataxia type 20, spinocerebellar ataxia type 25, spinocerebellar ataxia type 8, spinocerebellar ataxia type 27, spinocerebellar ataxia type 28, spinocerebellar ataxia type 35, spinocerebellar ataxia type 32, spinocerebellar ataxia type 36, cerebellar dysfunction with variable cognitive and behavioral abnormalities, spinocerebellar ataxia type 37, spinocerebellar ataxia type 40, spinocerebellar ataxia 46, neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism

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

73 retrieved; paginated sample, class counts are floors:

37 uncertain significance, 17 benign, 10 conflicting classifications of pathogenicity, 4 likely benign, 3 benign/likely benign, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
18459	NM_024411.5(PDYN):c.643C>T (p.Arg215Cys)	PDYN	Pathogenic	no assertion criteria provided
18461	NM_024411.5(PDYN):c.634C>T (p.Arg212Trp)	PDYN	Likely pathogenic	criteria provided, single submitter
1298300	NM_024411.5(PDYN):c.635G>A (p.Arg212Gln)	PDYN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
18458	NM_024411.5(PDYN):c.414G>T (p.Arg138Ser)	PDYN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
211896	NM_024411.5(PDYN):c.658_659del (p.Trp220fs)	PDYN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
337813	NM_024411.5(PDYN):c.*1071G>A	PDYN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
337831	NM_024411.5(PDYN):c.*231C>G	PDYN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
586213	NM_024411.5(PDYN):c.691C>A (p.Arg231=)	PDYN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
898048	NM_024411.5(PDYN):c.*760G>C	PDYN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
337836	NM_024411.5(PDYN):c.520C>T (p.Arg174Cys)	PDYN-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
447932	NM_024411.5(PDYN):c.716G>A (p.Arg239Gln)	PDYN-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
728105	NM_024411.5(PDYN):c.582C>T (p.Asp194=)	PDYN-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1806152	NM_024411.5(PDYN):c.630C>G (p.Phe210Leu)	PDYN	Uncertain significance	criteria provided, single submitter
18460	NM_024411.5(PDYN):c.632T>C (p.Leu211Ser)	PDYN	Uncertain significance	criteria provided, single submitter
190223	NM_024411.5(PDYN):c.217A>G (p.Thr73Ala)	PDYN	Uncertain significance	no assertion criteria provided
337806	NM_024411.5(PDYN):c.*1532C>T	PDYN	Uncertain significance	criteria provided, single submitter
337812	NM_024411.5(PDYN):c.*1157T>G	PDYN	Uncertain significance	criteria provided, single submitter
337816	NM_024411.5(PDYN):c.*847T>C	PDYN	Uncertain significance	criteria provided, single submitter
337825	NM_024411.5(PDYN):c.*522C>T	PDYN	Uncertain significance	criteria provided, single submitter
337837	NM_024411.5(PDYN):c.501C>T (p.Asp167=)	PDYN	Uncertain significance	criteria provided, single submitter
337841	NM_024411.5(PDYN):c.-42A>T	PDYN	Uncertain significance	criteria provided, single submitter
337842	NM_024411.5(PDYN):c.-162A>G	PDYN	Uncertain significance	criteria provided, single submitter
895049	NM_024411.5(PDYN):c.*556C>A	PDYN	Uncertain significance	criteria provided, single submitter
895051	NM_024411.5(PDYN):c.*320C>T	PDYN	Uncertain significance	criteria provided, single submitter
896420	NM_024411.5(PDYN):c.*1336G>C	PDYN	Uncertain significance	criteria provided, single submitter
896421	NM_024411.5(PDYN):c.*1065C>T	PDYN	Uncertain significance	criteria provided, single submitter
896495	NM_024411.5(PDYN):c.724G>A (p.Glu242Lys)	PDYN	Uncertain significance	criteria provided, multiple submitters, no conflicts
898047	NM_024411.5(PDYN):c.*872C>A	PDYN	Uncertain significance	criteria provided, single submitter
898117	NM_024411.5(PDYN):c.691C>T (p.Arg231Trp)	PDYN	Uncertain significance	criteria provided, multiple submitters, no conflicts
898118	NM_024411.5(PDYN):c.571G>T (p.Gly191Trp)	PDYN	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
PDYN	Strong	Autosomal dominant	spinocerebellar ataxia type 23	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PDYN	Orphanet:101108	Spinocerebellar ataxia type 23

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PDYN	HGNC:8820	ENSG00000101327	P01213	Proenkephalin-B	gencc,clinvar
PDYN-AS1	HGNC:53462	ENSG00000233896		PDYN antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PDYN	Proenkephalin-B	Leu-enkephalins compete with and mimic the effects of opiate drugs.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PDYN	Other/Unknown	no		Proenkphlin_B, Opioid_neupept
PDYN-AS1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
caudate nucleus	1
nucleus accumbens	1
putamen	1
bone marrow cell	1
granulocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PDYN	85	tissue_specific	marker	nucleus accumbens, caudate nucleus, putamen
PDYN-AS1	53	tissue_specific	yes	granulocyte, bone marrow cell, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDYN	2,052
PDYN-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PDYN	P01213	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
G-protein activation	1	475.8×	0.008	PDYN
Opioid Signalling	1	265.6×	0.008	PDYN
Peptide ligand-binding receptors	1	74.2×	0.018	PDYN
G alpha (i) signalling events	1	39.0×	0.026	PDYN

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
sensory perception	1	1404.3×	0.002	PDYN
neuropeptide signaling pathway	1	172.0×	0.009	PDYN
chemical synaptic transmission	1	77.3×	0.013	PDYN

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDYN	0	0
PDYN-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PDYN	1	Binding:1

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	2	PDYN, PDYN-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PDYN	1	—
PDYN-AS1	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