Spinocerebellar ataxia, autosomal recessive 25

Summary

Spinocerebellar ataxia, autosomal recessive 25 (MONDO:0033115) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia, autosomal recessive 25
Mondo ID	MONDO:0033115
OMIM	617584
DOID	DOID:0080259
UMLS	C4539808
MedGen	1618081
GARD	0025786
Is cancer (heuristic)	no

Also known as: SCAR25 · spinocerebellar ataxia, autosomal recessive 25

Data availability: 1 ClinVar variant · 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 recessive disease › autosomal recessive cerebellar ataxia › spinocerebellar ataxia, autosomal recessive 25

Related subtypes (28): Charlevoix-Saguenay spastic ataxia, infantile-onset autosomal recessive nonprogressive cerebellar ataxia, autosomal recessive spinocerebellar ataxia 7, autosomal recessive ataxia, Beauce type, RIDDLE syndrome, autosomal recessive ataxia due to ubiquinone deficiency, autosomal recessive spinocerebellar ataxia 10, ataxia with oculomotor apraxia type 3, autosomal recessive spinocerebellar ataxia 14, autosomal recessive spinocerebellar ataxia 16, Lichtenstein-Knorr syndrome, autosomal recessive spinocerebellar ataxia 20, spinocerebellar ataxia, autosomal recessive 22, spinocerebellar ataxia, autosomal recessive 24, autosomal recessive cerebellar ataxia - epilepsy - intellectual disability syndrome, autosomal recessive congenital cerebellar ataxia, autosomal recessive metabolic cerebellar ataxia, autosomal recessive degenerative and progressive cerebellar ataxia, autosomal recessive syndromic cerebellar ataxia, spinocerebellar ataxia, autosomal recessive, with axonal neuropathy, spinocerebellar ataxia, autosomal recessive 29, spinocerebellar ataxia, autosomal recessive 30, spinocerebellar ataxia, autosomal recessive 31, spinocerebellar ataxia, autosomal recessive 27, spinocerebellar ataxia, autosomal recessive 28, spinocerebellar ataxia, autosomal recessive 26, spinocerebellar ataxia, autosomal recessive 32, spinocerebellar ataxia, autosomal recessive 33

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

1 retrieved; paginated sample, class counts are floors:

1 no classifications from unflagged records

ClinVar	Variant (HGVS)	Gene	Classification	Review
430932	NM_004849.4(ATG5):c.366A>T (p.Glu122Asp)	ATG5	no classifications from unflagged records	no classifications from unflagged records

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
ATG5	Moderate	Autosomal recessive	spinocerebellar ataxia, autosomal recessive 25	3

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
ATG5	HGNC:589	ENSG00000057663	Q9H1Y0	Autophagy protein 5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATG5	Autophagy protein 5	Involved in autophagic vesicle formation.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATG5	Other/Unknown	no		Atg5, Atg5_HR, Atg5_UblA_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
colonic mucosa	1
mucosa of sigmoid colon	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATG5	283	ubiquitous	marker	primordial germ cell in gonad, colonic mucosa, mucosa of sigmoid colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATG5	4,799

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATG5	Q9H1Y0	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Mitophagy	1	1038.2×	0.005	ATG5
Receptor Mediated Mitophagy	1	1038.2×	0.005	ATG5
PINK1-PRKN Mediated Mitophagy	1	356.9×	0.007	ATG5
Negative regulators of DDX58/IFIH1 signaling	1	326.3×	0.007	ATG5
Selective autophagy	1	278.5×	0.007	ATG5
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1	253.8×	0.007	ATG5
Autophagy	1	148.3×	0.010	ATG5
Macroautophagy	1	115.3×	0.011	ATG5
Innate Immune System	1	25.5×	0.044	ATG5
Immune System	1	13.0×	0.077	ATG5

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
antigen processing and presentation of endogenous antigen	1	8426.0×	0.001	ATG5
otolith development	1	8426.0×	0.001	ATG5
positive regulation of viral translation	1	8426.0×	0.001	ATG5
negative stranded viral RNA replication	1	5617.3×	0.001	ATG5
cellular response to nitrosative stress	1	5617.3×	0.001	ATG5
response to fluoride	1	5617.3×	0.001	ATG5
negative regulation of autophagic cell death	1	5617.3×	0.001	ATG5
regulation of cytokine production involved in immune response	1	4213.0×	0.001	ATG5
response to fungus	1	4213.0×	0.001	ATG5
axonal transport	1	4213.0×	0.001	ATG5
positive regulation of stress granule assembly	1	3370.4×	0.001	ATG5
positive regulation of mucus secretion	1	3370.4×	0.001	ATG5
chaperone-mediated autophagy	1	2808.7×	0.001	ATG5
regulation of autophagosome maturation	1	2808.7×	0.001	ATG5
response to iron(II) ion	1	2407.4×	0.001	ATG5
aggrephagy	1	1685.2×	0.002	ATG5
cellular response to nitrogen starvation	1	1532.0×	0.002	ATG5
ventricular cardiac muscle cell development	1	1532.0×	0.002	ATG5
negative thymic T cell selection	1	1404.3×	0.002	ATG5
negative regulation of defense response to virus	1	1296.3×	0.002	ATG5
mucus secretion	1	1296.3×	0.002	ATG5
cardiac muscle cell apoptotic process	1	1203.7×	0.002	ATG5
negative regulation of phagocytosis	1	991.3×	0.002	ATG5
piecemeal microautophagy of the nucleus	1	936.2×	0.002	ATG5
regulation of release of sequestered calcium ion into cytosol	1	936.2×	0.002	ATG5
heart contraction	1	766.0×	0.002	ATG5
regulation of reactive oxygen species metabolic process	1	732.7×	0.002	ATG5
postsynaptic modulation of chemical synaptic transmission	1	674.1×	0.002	ATG5
regulation of cilium assembly	1	601.9×	0.003	ATG5
negative regulation of cardiac muscle cell apoptotic process	1	543.6×	0.003	ATG5

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
ATG5	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	ATG5

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)
ATG5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.