Spinocerebellar ataxia 7

Summary

Spinocerebellar ataxia 7 (MONDO:0016163) is a disease caused by ATXN7 (GenCC Definitive), with 2 cohort genes and 6 clinical trials. Top therapeutic interventions include riluzole, troriluzole, and rimtuzalcap.

At a glance

• Prevalence: 1-9 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ATXN7 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 10
• Phenotypes (HPO): 32
• Clinical trials: 6

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

32 HPO clinical features (Orphanet curated; top 32 by frequency):

HPO ID	Term	Frequency
HP:0001251	Ataxia	Obligate (100%)
HP:0001260	Dysarthria	Obligate (100%)
HP:0001310	Dysmetria	Obligate (100%)
HP:0001347	Hyperreflexia	Obligate (100%)
HP:0000548	Cone/cone-rod dystrophy	Very frequent (80-99%)
HP:0002015	Dysphagia	Very frequent (80-99%)
HP:0000572	Visual loss	Frequent (30-79%)
HP:0000597	Ophthalmoparesis	Frequent (30-79%)
HP:0000602	Ophthalmoplegia	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0001098	Abnormal fundus morphology	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001268	Mental deterioration	Frequent (30-79%)
HP:0001270	Motor delay	Frequent (30-79%)
HP:0001272	Cerebellar atrophy	Frequent (30-79%)
HP:0001319	Neonatal hypotonia	Frequent (30-79%)
HP:0001324	Muscle weakness	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001635	Congestive heart failure	Frequent (30-79%)
HP:0002059	Cerebral atrophy	Frequent (30-79%)
HP:0002075	Dysdiadochokinesis	Frequent (30-79%)
HP:0002310	Orofacial dyskinesia	Frequent (30-79%)
HP:0003474	Somatic sensory dysfunction	Frequent (30-79%)
HP:0003487	Babinski sign	Frequent (30-79%)
HP:0007663	Reduced visual acuity	Frequent (30-79%)
HP:0011968	Feeding difficulties	Frequent (30-79%)
HP:0012452	Restless legs	Frequent (30-79%)
HP:0000608	Macular degeneration	Occasional (5-29%)
HP:0000613	Photophobia	Occasional (5-29%)
HP:0000618	Blindness	Occasional (5-29%)
HP:0000709	Psychosis	Occasional (5-29%)
HP:0012047	Hemeralopia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia 7
Mondo ID	MONDO:0016163
OMIM	164500
Orphanet	208508, 94147
DOID	DOID:0050958
NCIT	C126562
SNOMED CT	715726000
UMLS	C0752125
MedGen	156006
GARD	0020405
Is cancer (heuristic)	no

Also known as: ADCA, type II · ADCA2 · ADCAII · ataxia with pigmentary retinopathy · ATXN7 autosomal dominant cerebellar ataxia type II · autosomal dominant cerebellar ataxia type 2 · autosomal dominant cerebellar ataxia type II · autosomal dominant cerebellar ataxia type II caused by mutation in ATXN7 · cerebellar syndrome-pigmentary maculopathy syndrome · OPCA III · OPCA3 · SCA7 · spinocerebellar ataxia 7 · spinocerebellar ataxia type 7

Data availability: 10 ClinVar variants · 2 GenCC gene-disease records · 12 cell lines.

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 › spinocerebellar ataxia 7

Related subtypes (15): GRID2-related autosomal dominant spinocerebellar ataxia, spinocerebellar ataxia 27A, spinocerebellar ataxia 9, spinocerebellar ataxia 43, autosomal dominant cerebellar ataxia type I, autosomal dominant cerebellar ataxia type III, autosomal dominant cerebellar ataxia type IV, spinocerebellar ataxia 49, spinocerebellar ataxia 48, spinocerebellar ataxia 44, spinocerebellar ataxia 47, spinocerebellar ataxia 50, spinocerebellar ataxia 27B, late-onset, spinocerebellar ataxia 51, spinocerebellar ataxia 52

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:

6 uncertain significance, 2 benign, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
562100	NG_008227.1:g.53130CAG[38_130]	ATXN7	Pathogenic	no assertion criteria provided
626311	NM_001377405.1(ATXN7):c.89AGC[233] (p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln)	ATXN7	Pathogenic	criteria provided, single submitter
1298305	NM_001377405.1(ATXN7):c.2528C>T (p.Ser843Leu)	ATXN7	Uncertain significance	criteria provided, single submitter
1691553	NM_001377405.1(ATXN7):c.2120G>A (p.Arg707His)	ATXN7	Uncertain significance	criteria provided, single submitter
3589518	NM_001377405.1(ATXN7):c.1373G>A (p.Cys458Tyr)	ATXN7	Uncertain significance	criteria provided, single submitter
638341	NM_001377405.1(ATXN7):c.1594G>A (p.Gly532Ser)	ATXN7	Uncertain significance	criteria provided, single submitter
638436	NM_001377405.1(ATXN7):c.112_113insCGCCGC (p.Gln37_Gln38insProPro)	ATXN7	Uncertain significance	criteria provided, single submitter
3764751	NC_000023.11:g.103577174dup	TCEAL4	Uncertain significance	no assertion criteria provided
2953	NM_000333.4:c.89ACG[7_17]	ATXN7	Benign	no assertion criteria provided
931863	NM_001377405.1(ATXN7):c.2654_2656del (p.Leu885del)	ATXN7	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
ATXN7	Definitive	Autosomal dominant	spinocerebellar ataxia 7	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATXN7	Orphanet:94147	Spinocerebellar ataxia type 7

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
ATXN7	HGNC:10560	ENSG00000163635	O15265	Ataxin-7	gencc,clinvar
TCEAL4	HGNC:26121	ENSG00000133142	Q96EI5	Transcription elongation factor A protein-like 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATXN7	Ataxin-7	Acts as a component of the SAGA (aka STAGA) transcription coactivator-HAT complex.
TCEAL4	Transcription elongation factor A protein-like 4	May be involved in transcriptional regulation.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATXN7	Other/Unknown	no		SCA7_dom, Ataxin-7-like_regulator
TCEAL4	Transcription factor	no		TF_A-like/BEX

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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
jejunal mucosa	1
mucosa of paranasal sinus	1
superficial temporal artery	1
body of uterus	1
left ovary	1
right ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATXN7	290	ubiquitous	marker	mucosa of paranasal sinus, jejunal mucosa, superficial temporal artery
TCEAL4	294	ubiquitous	marker	right ovary, left ovary, body of uterus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATXN7	1,788
TCEAL4	871

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATXN7	O15265	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TCEAL4	Q96EI5	61.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Deubiquitination	1	124.1×	0.024	ATXN7
Chromatin organization	1	81.6×	0.024	ATXN7
HATs acetylate histones	1	79.3×	0.024	ATXN7
Chromatin modifying enzymes	1	72.3×	0.024	ATXN7
Ub-specific processing proteases	1	53.1×	0.026	ATXN7
Post-translational protein modification	1	19.2×	0.061	ATXN7
Metabolism of proteins	1	12.4×	0.081	ATXN7

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
nucleus organization	1	561.7×	0.008	ATXN7
negative regulation of microtubule depolymerization	1	495.6×	0.008	ATXN7
regulation of DNA repair	1	276.3×	0.009	ATXN7
regulation of RNA splicing	1	218.9×	0.009	ATXN7
microtubule cytoskeleton organization	1	121.2×	0.013	ATXN7
visual perception	1	79.5×	0.017	ATXN7
positive regulation of DNA-templated transcription	1	27.9×	0.041	ATXN7
regulation of transcription by RNA polymerase II	1	11.7×	0.086	ATXN7

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
ATXN7	0	0
TCEAL4	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
ATXN7	5	Binding:5

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	ATXN7, TCEAL4

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)
ATXN7	5	—
TCEAL4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3
PHASE2/PHASE3	1
PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03660917	PHASE2/PHASE3	RECRUITING	Riluzole in Patients With Spinocerebellar Ataxia Type 7
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
NCT05826171	Not specified	ACTIVE_NOT_RECRUITING	Priming Motor Learning Through Exercise in People With Spinocerebellar Ataxia
NCT04288128	Not specified	COMPLETED	Integrated Functional Evaluation of the Cerebellum

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
RILUZOLE	4	1
TRORILUZOLE	3	1
RIMTUZALCAP	2	1