Spinocerebellar ataxia, autosomal recessive 24

Summary

Spinocerebellar ataxia, autosomal recessive 24 (MONDO:0014934) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia, autosomal recessive 24
Mondo ID	MONDO:0014934
OMIM	617133
DOID	DOID:0111615
UMLS	C4310699
MedGen	934666
GARD	0025035
Is cancer (heuristic)	no

Also known as: autosomal recessive cerebellar ataxia caused by mutation in UBA5 · SCAR24 · spinocerebellar ataxia, autosomal recessive 24 · spinocerebellar ataxia, autosomal recessive 24; SCAR24 · spinocerebellar ataxia, autosomal recessive type 24 · UBA5 autosomal recessive cerebellar ataxia

Data availability: 10 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 recessive disease › autosomal recessive cerebellar ataxia › spinocerebellar ataxia, autosomal recessive 24

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, 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 25, 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

10 retrieved; paginated sample, class counts are floors:

2 pathogenic/likely pathogenic, 2 pathogenic, 2 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 benign, 1 pathogenic/likely pathogenic/pathogenic, low penetrance, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1197851	NM_024818.6(UBA5):c.799C>T (p.Gln267Ter)	NPHP3-ACAD11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265745	NM_024818.6(UBA5):c.1111G>A (p.Ala371Thr)	NPHP3-ACAD11	Pathogenic/Likely pathogenic/Pathogenic, low penetrance	criteria provided, multiple submitters, no conflicts
265756	NM_024818.6(UBA5):c.736C>T (p.Arg246Ter)	NPHP3-ACAD11	Pathogenic	no assertion criteria provided
265757	NM_024818.6(UBA5):c.928A>G (p.Lys310Glu)	NPHP3-ACAD11	Pathogenic	no assertion criteria provided
265749	NM_024818.6(UBA5):c.562C>T (p.Arg188Ter)	UBA5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3024304	NM_024818.6(UBA5):c.542G>A (p.Cys181Tyr)	NPHP3-ACAD11	Likely pathogenic	criteria provided, single submitter
4845701	NM_024818.4:c.-823C>A	UBA5	Likely pathogenic	criteria provided, single submitter
1409798	NM_024818.6(UBA5):c.214C>T (p.Arg72Cys)	NPHP3-ACAD11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3382847	NM_024818.6(UBA5):c.692C>T (p.Pro231Leu)	NPHP3-ACAD11	Uncertain significance	criteria provided, single submitter
1684231	NM_024818.6(UBA5):c.1024+32T>C	UBA5	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
UBA5	Moderate	Autosomal recessive	spinocerebellar ataxia, autosomal recessive 24	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UBA5	Orphanet:442835	Non-specific early-onset epileptic encephalopathy

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
UBA5	HGNC:23230	ENSG00000081307	Q9GZZ9	Ubiquitin-like modifier-activating enzyme 5	gencc,clinvar
NPHP3-ACAD11	HGNC:48351	ENSG00000274810		NPHP3-ACAD11 readthrough (NMD candidate)	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UBA5	Ubiquitin-like modifier-activating enzyme 5	E1-like enzyme which specifically catalyzes the first step in ufmylation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UBA5	Enzyme (other)	yes	6.2.1.45	ThiF_NAD_FAD-bd, D-isomer_DH_CS1, Ubiquitin-activating_enz
NPHP3-ACAD11	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
body of pancreas	1
right adrenal gland	1
right adrenal gland cortex	1
calcaneal tendon	1
endometrium	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UBA5	287	ubiquitous	marker	body of pancreas, right adrenal gland, right adrenal gland cortex
NPHP3-ACAD11	133	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UBA5	2,500
NPHP3-ACAD11	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
UBA5	Q9GZZ9	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Dengue Virus Attachment and Entry	1	259.6×	0.008	UBA5
Antigen processing: Ubiquitination & Proteasome degradation	1	37.2×	0.027	UBA5

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
protein K69-linked ufmylation	1	3370.4×	0.001	UBA5
protein ufmylation	1	2407.4×	0.001	UBA5
regulation of type II interferon production	1	2106.5×	0.001	UBA5
regulation of intracellular estrogen receptor signaling pathway	1	1872.4×	0.001	UBA5
megakaryocyte differentiation	1	1203.7×	0.001	UBA5
reticulophagy	1	702.2×	0.002	UBA5
neuromuscular process	1	526.6×	0.002	UBA5
erythrocyte differentiation	1	267.5×	0.004	UBA5
response to endoplasmic reticulum stress	1	166.8×	0.006	UBA5

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
UBA5	0	0
NPHP3-ACAD11	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
UBA5	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
UBA5	6.2.1.45	E1 ubiquitin-activating enzyme

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	1	UBA5
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	NPHP3-ACAD11

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)
UBA5	2	—
NPHP3-ACAD11	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.