Spinocerebellar ataxia type 25

disease

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Also known as SCA25spinocerebellar ataxia 25

Summary

Spinocerebellar ataxia type 25 (MONDO:0012103) is a disease with 1 cohort gene and 1 clinical trial.

At a glance

Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
Cohort genes: 1
ClinVar variants: 15
Phenotypes (HPO): 23
Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		10	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

23 HPO clinical features (Orphanet curated; top 23 by frequency):

HPO ID	Term	Frequency
HP:0002073	Progressive cerebellar ataxia	Very frequent (80-99%)
HP:0007328	Impaired pain sensation	Frequent (30-79%)
HP:0007663	Reduced visual acuity	Frequent (30-79%)
HP:0011468	Facial tics	Frequent (30-79%)
HP:0031422	Abnormal morphology of the cerebellar cortex	Frequent (30-79%)
HP:0100275	Diffuse cerebellar atrophy	Frequent (30-79%)
HP:0000012	Urinary urgency	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0000763	Sensory neuropathy	Frequent (30-79%)
HP:0001761	Pes cavus	Frequent (30-79%)
HP:0002066	Gait ataxia	Frequent (30-79%)
HP:0002464	Spastic dysarthria	Frequent (30-79%)
HP:0002522	Areflexia of lower limbs	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0002936	Distal sensory impairment	Frequent (30-79%)
HP:0003387	Decreased number of large peripheral myelinated nerve fibers	Frequent (30-79%)
HP:0003445	EMG: neuropathic changes	Frequent (30-79%)
HP:0003487	Babinski sign	Frequent (30-79%)
HP:0006937	Impaired distal tactile sensation	Frequent (30-79%)
HP:0000317	Facial myokymia	Occasional (5-29%)
HP:0002013	Vomiting	Occasional (5-29%)
HP:0002574	Episodic abdominal pain	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia type 25
Mondo ID	MONDO:0012103
MeSH	C537202
OMIM	608703
Orphanet	101111
DOID	DOID:0050974
ICD-11	8347192
SNOMED CT	718770005
UMLS	C1837518
MedGen	373347
GARD	0009996
Is cancer (heuristic)	no

Also known as: SCA25 · spinocerebellar ataxia 25

Data availability: 15 ClinVar variants · 2 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 25

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

15 retrieved; paginated sample, class counts are floors:

5 likely pathogenic, 4 uncertain significance, 4 conflicting classifications of pathogenicity, 1 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1695428	NM_033109.5(PNPT1):c.2069+3A>G	PNPT1	Pathogenic	no assertion criteria provided
215010	NM_033109.5(PNPT1):c.1519G>T (p.Ala507Ser)	PNPT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1695429	NM_033109.5(PNPT1):c.2014-3C>G	PNPT1	Likely pathogenic	criteria provided, single submitter
3220865	NM_033109.5(PNPT1):c.162-2A>C	PNPT1	Likely pathogenic	criteria provided, single submitter
3775873	NM_033109.5(PNPT1):c.2143C>T (p.Arg715Ter)	PNPT1	Likely pathogenic	criteria provided, single submitter
3780459	NM_033109.5(PNPT1):c.984del (p.Pro329fs)	PNPT1	Likely pathogenic	criteria provided, single submitter
4277372	NM_033109.5(PNPT1):c.2043del (p.Tyr682fs)	PNPT1	Likely pathogenic	criteria provided, single submitter
1342762	NM_033109.5(PNPT1):c.40C>T (p.Arg14Trp)	PNPT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
209185	NM_033109.5(PNPT1):c.1525G>A (p.Val509Ile)	PNPT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
215005	NM_033109.5(PNPT1):c.493C>T (p.Pro165Ser)	PNPT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
996028	NM_033109.5(PNPT1):c.2213G>A (p.Arg738His)	PNPT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1015538	NM_033109.5(PNPT1):c.2039C>T (p.Ala680Val)	PNPT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1370924	NM_033109.5(PNPT1):c.1972C>T (p.His658Tyr)	PNPT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1482633	NM_033109.5(PNPT1):c.736A>G (p.Lys246Glu)	PNPT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3906987	NM_033109.5(PNPT1):c.2182G>A (p.Gly728Ser)	PNPT1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 3 · 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
PNPT1	Moderate	Autosomal dominant	spinocerebellar ataxia type 25	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PNPT1	Orphanet:101111	Spinocerebellar ataxia type 25
PNPT1	Orphanet:319514	Combined oxidative phosphorylation defect type 13
PNPT1	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

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
PNPT1	HGNC:23166	ENSG00000138035	Q8TCS8	Polyribonucleotide nucleotidyltransferase 1, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PNPT1	Polyribonucleotide nucleotidyltransferase 1, mitochondrial	RNA-binding protein implicated in numerous RNA metabolic processes.

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)
PNPT1	Scaffold/PPI	no	2.7.7.8	ExoRNase_PH_dom1, S1_domain, KH_dom

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
left ventricle myocardium	1
secondary oocyte	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PNPT1	258	ubiquitous	marker	left ventricle myocardium, secondary oocyte, tibialis anterior

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PNPT1	3,741

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PNPT1	Q8TCS8	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 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
Mitochondrial RNA degradation	1	1631.4×	6e-04	PNPT1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
RNA import into mitochondrion	1	16852.0×	6e-04	PNPT1
nuclear polyadenylation-dependent mRNA catabolic process	1	16852.0×	6e-04	PNPT1
mitochondrial RNA 5’-end processing	1	8426.0×	6e-04	PNPT1
mitochondrial mRNA catabolic process	1	5617.3×	6e-04	PNPT1
positive regulation of mitochondrial RNA catabolic process	1	5617.3×	6e-04	PNPT1
mitochondrial RNA 3’-end processing	1	5617.3×	6e-04	PNPT1
rRNA import into mitochondrion	1	5617.3×	6e-04	PNPT1
mitochondrial mRNA polyadenylation	1	4213.0×	6e-04	PNPT1
positive regulation of miRNA catabolic process	1	4213.0×	6e-04	PNPT1
mitochondrial RNA catabolic process	1	2808.7×	8e-04	PNPT1
regulation of cellular respiration	1	2808.7×	8e-04	PNPT1
regulation of cellular senescence	1	1404.3×	0.001	PNPT1
positive regulation of mRNA catabolic process	1	1203.7×	0.002	PNPT1
response to growth hormone	1	1123.5×	0.002	PNPT1
protein homotrimerization	1	991.3×	0.002	PNPT1
cellular response to interferon-beta	1	526.6×	0.003	PNPT1
response to cAMP	1	510.7×	0.003	PNPT1
liver regeneration	1	510.7×	0.003	PNPT1
mRNA catabolic process	1	495.6×	0.003	PNPT1
RNA catabolic process	1	455.5×	0.003	PNPT1
cellular response to oxidative stress	1	154.6×	0.007	PNPT1
mitochondrion organization	1	151.8×	0.007	PNPT1
protein homooligomerization	1	122.1×	0.009	PNPT1
mRNA processing	1	78.8×	0.013	PNPT1

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
PNPT1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PNPT1	2.7.7.8	polyribonucleotide nucleotidyltransferase

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	PNPT1

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)
PNPT1	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: PNPT1