Spinocerebellar ataxia type 10

Summary

Spinocerebellar ataxia type 10 (MONDO:0011330) is a disease caused by ATXN10 (GenCC Strong), with 1 cohort gene and 4 clinical trials. Top therapeutic interventions include troriluzole and rimtuzalcap.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: ATXN10 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 13
• Phenotypes (HPO): 30
• Clinical trials: 4

Clinical features

Signs & symptoms

Clinical features (HPO)

30 HPO clinical features (Orphanet curated; top 30 by frequency):

HPO ID	Term	Frequency
HP:0001260	Dysarthria	Very frequent (80-99%)
HP:0002066	Gait ataxia	Very frequent (80-99%)
HP:0002073	Progressive cerebellar ataxia	Very frequent (80-99%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0000640	Gaze-evoked nystagmus	Frequent (30-79%)
HP:0001272	Cerebellar atrophy	Frequent (30-79%)
HP:0001310	Dysmetria	Frequent (30-79%)
HP:0002075	Dysdiadochokinesis	Frequent (30-79%)
HP:0002080	Intention tremor	Frequent (30-79%)
HP:0002141	Gait imbalance	Frequent (30-79%)
HP:0002168	Scanning speech	Frequent (30-79%)
HP:0002197	Generalized-onset seizure	Frequent (30-79%)
HP:0002317	Unsteady gait	Frequent (30-79%)
HP:0007772	Impaired smooth pursuit	Frequent (30-79%)
HP:0011198	EEG with generalized epileptiform discharges	Frequent (30-79%)
HP:0030186	Kinetic tremor	Frequent (30-79%)
HP:0100660	Dyskinesia	Frequent (30-79%)
HP:0000012	Urinary urgency	Occasional (5-29%)
HP:0000716	Depression	Occasional (5-29%)
HP:0000718	Aggressive behavior	Occasional (5-29%)
HP:0000741	Apathy	Occasional (5-29%)
HP:0001265	Hyporeflexia	Occasional (5-29%)
HP:0001290	Generalized hypotonia	Occasional (5-29%)
HP:0001347	Hyperreflexia	Occasional (5-29%)
HP:0002061	Lower limb spasticity	Occasional (5-29%)
HP:0002133	Status epilepticus	Occasional (5-29%)
HP:0002360	Sleep abnormality	Occasional (5-29%)
HP:0002384	Focal impaired awareness seizure	Occasional (5-29%)
HP:0003487	Babinski sign	Occasional (5-29%)
HP:0011153	Focal motor seizure	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia type 10
Mondo ID	MONDO:0011330
MeSH	C566874
OMIM	603516
Orphanet	98761
DOID	DOID:0050960
ICD-11	157300879
SNOMED CT	715754007
UMLS	C1963674
MedGen	369786
GARD	0010474
Is cancer (heuristic)	no

Also known as: SCA10 · spinocerebellar ataxia 10 · spinocerebellar ataxia type 10

Data availability: 13 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 IV › spinocerebellar ataxia type 10

Related subtypes (1): dentatorubral-pallidoluysian atrophy

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

13 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 4 pathogenic, 1 likely benign, 1 not provided, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
39003	NM_013236.3(ATXN10):c.1173+54822_1173+54826ATTCT(360_370)	ATXN10	Pathogenic	no assertion criteria provided
39004	NM_013236.3(ATXN10):c.1173+54822_1173+54826ATTCT(400_760)	ATXN10	Pathogenic	no assertion criteria provided
39006	NM_013236.3(ATXN10):c.1173+54822_1173+54826ATTCT[850]	ATXN10	Pathogenic	no assertion criteria provided
39005	NM_013236.3(ATXN10):c.1173+54822_1173+54826ATTCT(800_4500)	LOC107181287	Pathogenic	no assertion criteria provided
1298306	NM_013236.4(ATXN10):c.404G>T (p.Gly135Val)	ATXN10	Uncertain significance	no assertion criteria provided
1708088	NM_013236.4(ATXN10):c.1165C>T (p.Gln389Ter)	ATXN10	Uncertain significance	criteria provided, single submitter
3065797	NM_013236.4(ATXN10):c.647+1G>A	ATXN10	Uncertain significance	criteria provided, single submitter
3779389	NM_013236.4(ATXN10):c.1174-11604ATTCT[13]	ATXN10	Uncertain significance	criteria provided, single submitter
930239	NM_013236.4(ATXN10):c.13A>G (p.Arg5Gly)	ATXN10	Uncertain significance	criteria provided, single submitter
930719	NM_013236.4(ATXN10):c.116+4A>T	LOC130067689	Uncertain significance	criteria provided, single submitter
196455	NM_013236.4(ATXN10):c.321G>A (p.Thr107=)	ATXN10	Likely benign	criteria provided, multiple submitters, no conflicts
999	NM_013236.5(ATXN10):c.1173+54822_1173ATTCT[10_32]	ATXN10	Benign	no assertion criteria provided
39007	NM_013236.3(ATXN10):c.1173+54822_1173+54826ATTCT[280]	ATXN10	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
ATXN10	Strong	Autosomal dominant	spinocerebellar ataxia type 10	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATXN10	Orphanet:98761	Spinocerebellar ataxia type 10

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
ATXN10	HGNC:10549	ENSG00000130638	Q9UBB4	Ataxin-10	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATXN10	Ataxin-10	May play a role in the regulation of cytokinesis.

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)
ATXN10	Other/Unknown	no		ARM-like, ARM-type_fold, Ataxin-10_domain

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
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATXN10	298	ubiquitous	marker	cortical plate, ventricular zone, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATXN10	1,589

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATXN10	Q9UBB4	90.03

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
regulation of cytokinesis	1	421.3×	0.012	ATXN10
neuron projection development	1	122.1×	0.020	ATXN10
cilium assembly	1	73.6×	0.022	ATXN10
cell division	1	46.2×	0.022	ATXN10
nervous system development	1	45.9×	0.022	ATXN10

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATXN10	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
ATXN10	7	Binding:7

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	ATXN10

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)
ATXN10	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2
PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03701399	PHASE3	ACTIVE_NOT_RECRUITING	Troriluzole in Adult Participants With Spinocerebellar Ataxia
NCT04301284	PHASE2	WITHDRAWN	Study of CAD-1883 for Spinocerebellar Ataxia
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04495426	Not specified	UNKNOWN	Genetic Mechanism of Conserved Ancestral Haplotype in SCA10

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TRORILUZOLE	3	1
RIMTUZALCAP	2	1