Spinocerebellar ataxia type 8

disease

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Also known as SCA8spinocerebellar ataxia 8

Summary

Spinocerebellar ataxia type 8 (MONDO:0012116) is a disease with 2 cohort genes and 3 clinical trials. Top therapeutic interventions include troriluzole and rimtuzalcap.

At a glance

Prevalence: Unknown (Worldwide)
Cohort genes: 2
ClinVar variants: 4
Phenotypes (HPO): 23
Clinical trials: 3

Clinical features

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0000802	Impotence	Frequent (30-79%)
HP:0001251	Ataxia	Frequent (30-79%)
HP:0001257	Spasticity	Frequent (30-79%)
HP:0001272	Cerebellar atrophy	Frequent (30-79%)
HP:0001332	Dystonia	Frequent (30-79%)
HP:0001347	Hyperreflexia	Frequent (30-79%)
HP:0002063	Rigidity	Frequent (30-79%)
HP:0002066	Gait ataxia	Frequent (30-79%)
HP:0002067	Bradykinesia	Frequent (30-79%)
HP:0002070	Limb ataxia	Frequent (30-79%)
HP:0002172	Postural instability	Frequent (30-79%)
HP:0002317	Unsteady gait	Frequent (30-79%)
HP:0002464	Spastic dysarthria	Frequent (30-79%)
HP:0006855	Cerebellar vermis atrophy	Frequent (30-79%)
HP:0000020	Urinary incontinence	Occasional (5-29%)
HP:0000273	Facial grimacing	Occasional (5-29%)
HP:0000716	Depression	Occasional (5-29%)
HP:0002015	Dysphagia	Occasional (5-29%)
HP:0002495	Impaired vibratory sensation	Occasional (5-29%)
HP:0002835	Aspiration	Occasional (5-29%)
HP:0007772	Impaired smooth pursuit	Occasional (5-29%)
HP:0012110	Hypoplasia of the pons	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia type 8
Mondo ID	MONDO:0012116
OMIM	608768
Orphanet	98760
DOID	DOID:0050959
ICD-11	1735913595
SNOMED CT	715753001
UMLS	C1837454
MedGen	332457
GARD	0004956
Is cancer (heuristic)	no

Also known as: SCA8 · spinocerebellar ataxia 8 · spinocerebellar ataxia type 8

Data availability: 4 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 8

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

4 retrieved; paginated sample, class counts are floors:

2 likely pathogenic, 1 benign, 1 pathogenic; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
562101	NR_002717.2(ATXN8OS):n.1103CTG[(107_127)]	ATXN8	Pathogenic; risk factor	no assertion criteria provided
3257724	NR_002717.2:n.894CTA[(3)]CTG[(317_330)]	ATXN8OS	Likely pathogenic	criteria provided, single submitter
3897714	NR_002717.2:n.894CTA[1]CTG[144_150]	ATXN8OS	Likely pathogenic	criteria provided, single submitter
192	NR_002717.2(ATXN8OS):n.1103CTG[15_40]	ATXN8	Benign	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 2 · 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
ATXN8	Moderate	Autosomal dominant	spinocerebellar ataxia type 8	2
ATXN8OS	Moderate	Autosomal dominant	spinocerebellar ataxia type 8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATXN8OS	Orphanet:98760	Spinocerebellar ataxia type 8
ATXN8	Orphanet:98760	Spinocerebellar ataxia type 8

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ATXN8OS	HGNC:10561	ENSG00000230223	P0DMR3	Putative protein ATXN8OS	gencc,clinvar
ATXN8	HGNC:32925	ENSG00000288330	Q156A1	Ataxin-8	gencc,clinvar

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)
ATXN8OS	Other/Unknown	no
ATXN8	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
male germ line stem cell (sensu Vertebrata) in testis	1
pleura	1
primordial germ cell in gonad	1
bone marrow cell	1
cortical plate	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATXN8OS	110		marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, pleura
ATXN8	35			bone marrow cell, cortical plate, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATXN8OS	0
ATXN8	0

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATXN8	Q156A1	97.39
ATXN8OS	P0DMR3	38.88

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
ATXN8OS	0	0
ATXN8	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	ATXN8OS, ATXN8

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)
ATXN8OS	0	—
ATXN8	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	1
PHASE2	1
Not specified	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

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TRORILUZOLE	3	1
RIMTUZALCAP	2	1

Cohort genes: ATXN8OS, ATXN8
Drugs: Troriluzole