Spinocerebellar ataxia type 17

Summary

Spinocerebellar ataxia type 17 (MONDO:0011781) is a disease caused by TBP (GenCC Definitive), with 1 cohort gene and 2 clinical trials. Top therapeutic interventions include rimtuzalcap.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: TBP (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 11
• Phenotypes (HPO): 19
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		100	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated
Point prevalence	<1 / 1 000 000	0.047	Japan	Validated
Point prevalence	1-9 / 1 000 000	0.16	United Kingdom	Validated

Signs & symptoms

Clinical features (HPO)

19 HPO clinical features (Orphanet curated; top 19 by frequency):

HPO ID	Term	Frequency
HP:0001251	Ataxia	Very frequent (80-99%)
HP:0001288	Gait disturbance	Very frequent (80-99%)
HP:0000473	Torticollis	Frequent (30-79%)
HP:0000643	Blepharospasm	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0001257	Spasticity	Frequent (30-79%)
HP:0001268	Mental deterioration	Frequent (30-79%)
HP:0001272	Cerebellar atrophy	Frequent (30-79%)
HP:0001300	Parkinsonism	Frequent (30-79%)
HP:0001332	Dystonia	Frequent (30-79%)
HP:0002063	Rigidity	Frequent (30-79%)
HP:0002072	Chorea	Frequent (30-79%)
HP:0002529	Neuronal loss in central nervous system	Frequent (30-79%)
HP:0004305	Involuntary movements	Frequent (30-79%)
HP:0007058	Generalized cerebral atrophy/hypoplasia	Frequent (30-79%)
HP:0007256	Abnormal pyramidal sign	Frequent (30-79%)
HP:0007366	Atrophy/Degeneration affecting the brainstem	Frequent (30-79%)
HP:0012082	Cerebellar Purkinje layer atrophy	Frequent (30-79%)
HP:0002356	Writer’s cramp	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia type 17
Mondo ID	MONDO:0011781
MeSH	C563505, C564616, C565866
OMIM	164700, 213100, 607136
Orphanet	98759
DOID	DOID:0050967
ICD-11	1173627424
NCIT	C179861
SNOMED CT	719249005
UMLS	C1846707
MedGen	337637
GARD	0010469
Is cancer (heuristic)	no

Also known as: cerebelloparenchymal disorder II · CPD2 · HDL4 · Huntington disease-like 4 · olivopontocerebellar atrophy 5 · olivopontocerebellar atrophy type 5 · OPCA V · OPCA with dementia and extrapyramidal signs · SCA 17 · SCA17 · spinocerebellar ataxia 17 · spinocerebellar ataxia type 17

Data availability: 11 ClinVar variants · 4 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › cerebelloparenchymal disorder › spinocerebellar ataxia type 17

Related subtypes (1): myoclonic cerebellar dyssynergia

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

11 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 2 benign/likely benign, 2 pathogenic, 2 benign, 1 pathogenic; risk factor, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
2576597	NM_003194.5(TBP):c.225GCA[25] (p.Gln95_Ala96insGlnGlnGlnGlnGlnGln)	LOC108663996	Pathogenic	criteria provided, single submitter
3572894	NM_003194.5(TBP):c.215_216insGCAACAACAACAGCAGCAGCAGCAGCAGCAGCAGCAGCA (p.Gln95_Ala96insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln)	LOC108663996	Pathogenic	criteria provided, single submitter
562072	NG_008165.1:g.12526CAR[46_?]	LOC108663996	Pathogenic; risk factor	no assertion criteria provided
634587	NM_003194.5(TBP):c.221_222insGC (p.Gln75fs)	LOC108663996	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1299293	NM_003194.5(TBP):c.231_243del (p.Gln77fs)	LOC108663996	Uncertain significance	criteria provided, single submitter
3780695	NM_003194.5(TBP):c.216_217insT (p.Gln73fs)	LOC108663996	Uncertain significance	criteria provided, single submitter
1033982	NM_003194.5(TBP):c.410C>T (p.Pro137Leu)	TBP	Uncertain significance	criteria provided, multiple submitters, no conflicts
3065444	NM_003194.5(TBP):c.231del (p.Gln77fs)	LOC108663996	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
403524	NM_003194.5(TBP):c.228_229del (p.Gln77fs)	LOC108663996	Benign	criteria provided, multiple submitters, no conflicts
522261	NM_003194.5(TBP):c.216_218del (p.Gln95del)	LOC108663996	Benign	criteria provided, multiple submitters, no conflicts
130558	NM_003194.5(TBP):c.216A>G (p.Gln72=)	TBP	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

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
TBP	Definitive	Autosomal dominant	spinocerebellar ataxia type 17	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TBP	Orphanet:98759	Spinocerebellar ataxia type 17

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
TBP	HGNC:11588	ENSG00000112592	P20226	TATA-box-binding protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TBP	TATA-box-binding protein	The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription.

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)
TBP	Other/Unknown	no		TBP, TBP_dom_sf, TBP_CS

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
left testis	1
right testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TBP	246	ubiquitous	marker	left testis, right testis, testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TBP	7,225

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TBP	P20226	77

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 42. 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
RNA Polymerase III Transcription Initiation From Type 2 Promoter	1	423.0×	0.010	TBP
RNA Polymerase III Transcription Initiation From Type 1 Promoter	1	407.9×	0.010	TBP
RNA Polymerase III Transcription Initiation From Type 3 Promoter	1	407.9×	0.010	TBP
Positive epigenetic regulation of rRNA expression	1	346.1×	0.010	TBP
RNA Polymerase III Transcription Initiation	1	335.9×	0.010	TBP
RNA Polymerase I Transcription Termination	1	326.3×	0.010	TBP
RNA Polymerase III Transcription	1	326.3×	0.010	TBP
RNA Polymerase I Promoter Clearance	1	292.8×	0.010	TBP
RNA Polymerase I Transcription	1	285.5×	0.010	TBP
RNA Polymerase III Abortive And Retractive Initiation	1	278.5×	0.010	TBP
Negative epigenetic regulation of rRNA expression	1	259.6×	0.010	TBP
HIV Transcription Initiation	1	233.1×	0.010	TBP
RNA Polymerase II HIV Promoter Escape	1	233.1×	0.010	TBP
RNA Polymerase II Promoter Escape	1	233.1×	0.010	TBP
RNA Polymerase II Transcription Pre-Initiation And Promoter Opening	1	233.1×	0.010	TBP
RNA Polymerase II Transcription Initiation	1	233.1×	0.010	TBP
RNA Polymerase II Transcription Initiation And Promoter Clearance	1	233.1×	0.010	TBP
RNA Polymerase I Transcription Initiation	1	223.9×	0.010	TBP
Transcription of the HIV genome	1	173.0×	0.012	TBP
SIRT1 negatively regulates rRNA expression	1	170.4×	0.012	TBP
Late Phase of HIV Life Cycle	1	167.9×	0.012	TBP
HIV Life Cycle	1	160.8×	0.012	TBP
RNA polymerase II transcribes snRNA genes	1	154.3×	0.012	TBP
RNA Polymerase II Pre-transcription Events	1	137.6×	0.012	TBP
Regulation of TP53 Activity	1	132.8×	0.012	TBP
ESR-mediated signaling	1	128.3×	0.012	TBP
B-WICH complex positively regulates rRNA expression	1	121.5×	0.012	TBP
RNA Polymerase I Promoter Escape	1	121.5×	0.012	TBP
HIV Infection	1	119.0×	0.012	TBP
Regulation of TP53 Activity through Phosphorylation	1	117.7×	0.012	TBP

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
DNA-templated transcription initiation	1	936.2×	0.005	TBP
transcription by RNA polymerase III	1	766.0×	0.005	TBP
transcription initiation at RNA polymerase II promoter	1	374.5×	0.005	TBP
mRNA transcription by RNA polymerase II	1	330.4×	0.005	TBP
RNA polymerase II preinitiation complex assembly	1	271.8×	0.005	TBP
positive regulation of transcription initiation by RNA polymerase II	1	271.8×	0.005	TBP
transcription by RNA polymerase II	1	70.5×	0.016	TBP
spermatogenesis	1	35.2×	0.028	TBP

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
TBP	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	TBP

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)
TBP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
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
RIMTUZALCAP	2	1