Spinocerebellar ataxia type 29

Summary

Spinocerebellar ataxia type 29 (MONDO:0007298) is a disease caused by ITPR1 (GenCC Strong), with 2 cohort genes and 2 clinical trials.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: ITPR1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 83
• Phenotypes (HPO): 20
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		50	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

20 HPO clinical features (Orphanet curated; top 20 by frequency):

HPO ID	Term	Frequency
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0001260	Dysarthria	Very frequent (80-99%)
HP:0001310	Dysmetria	Very frequent (80-99%)
HP:0002066	Gait ataxia	Very frequent (80-99%)
HP:0002080	Intention tremor	Very frequent (80-99%)
HP:0002194	Delayed gross motor development	Very frequent (80-99%)
HP:0010862	Delayed fine motor development	Very frequent (80-99%)
HP:0000570	Abnormal saccadic eye movements	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0000657	Oculomotor apraxia	Frequent (30-79%)
HP:0001270	Motor delay	Frequent (30-79%)
HP:0001272	Cerebellar atrophy	Frequent (30-79%)
HP:0001290	Generalized hypotonia	Frequent (30-79%)
HP:0002075	Dysdiadochokinesis	Frequent (30-79%)
HP:0006855	Cerebellar vermis atrophy	Frequent (30-79%)
HP:0012434	Delayed social development	Frequent (30-79%)
HP:0100543	Cognitive impairment	Frequent (30-79%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0025405	Visual fixation instability	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	spinocerebellar ataxia type 29
Mondo ID	MONDO:0007298
MeSH	C537206
OMIM	117360
Orphanet	208513
DOID	DOID:0050978
ICD-11	359640365
SNOMED CT	715825009
UMLS	C1861732
MedGen	350085
GARD	0010480
Is cancer (heuristic)	no

Also known as: ACV · cerebellar ataxia early-onset nonprogressive · congenital nonprogressive spinocerebellar ataxia · SCA29 · spinocerebellar ataxia 29 · spinocerebellar ataxia 29, congenital nonprogressive · spinocerebellar ataxia type 29

Data availability: 83 ClinVar variants · 4 GenCC gene-disease records · 3 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 › autosomal dominant cerebellar ataxia type I › spinocerebellar ataxia type 29

Related subtypes (29): Machado-Joseph disease, spinocerebellar ataxia type 34, spinocerebellar ataxia type 1, spinocerebellar ataxia type 2, spinocerebellar ataxia type 4, cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome, autosomal dominant cerebellar ataxia, deafness and narcolepsy, spinocerebellar ataxia type 12, spinocerebellar ataxia type 13, spinocerebellar ataxia type 14, spinocerebellar ataxia type 15/16, spinocerebellar ataxia type 17, spinocerebellar ataxia type 19/22, spinocerebellar ataxia type 21, spinocerebellar ataxia type 18, spinocerebellar ataxia type 20, spinocerebellar ataxia type 25, spinocerebellar ataxia type 8, spinocerebellar ataxia type 27, spinocerebellar ataxia type 23, spinocerebellar ataxia type 28, spinocerebellar ataxia type 35, spinocerebellar ataxia type 32, spinocerebellar ataxia type 36, cerebellar dysfunction with variable cognitive and behavioral abnormalities, spinocerebellar ataxia type 37, spinocerebellar ataxia type 40, spinocerebellar ataxia 46, neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism

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

83 retrieved; paginated sample, class counts are floors:

24 uncertain significance, 14 conflicting classifications of pathogenicity, 10 likely pathogenic, 10 benign, 10 benign/likely benign, 6 pathogenic/likely pathogenic, 6 pathogenic, 3 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1027413	NM_001378452.1(ITPR1):c.722G>A (p.Arg241Lys)	ITPR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208786	NM_001378452.1(ITPR1):c.800C>T (p.Thr267Met)	ITPR1	Pathogenic	criteria provided, multiple submitters, no conflicts
235922	NM_001378452.1(ITPR1):c.7660G>A (p.Gly2554Arg)	ITPR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
253023	NM_001378452.1(ITPR1):c.5504T>C (p.Leu1835Pro)	ITPR1	Pathogenic	no assertion criteria provided
2579948	NM_001378452.1(ITPR1):c.1700A>G (p.Tyr567Cys)	ITPR1	Pathogenic	criteria provided, multiple submitters, no conflicts
265201	NM_001378452.1(ITPR1):c.805C>T (p.Arg269Trp)	ITPR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39572	NM_001378452.1(ITPR1):c.1804A>G (p.Asn602Asp)	ITPR1	Pathogenic	no assertion criteria provided
503523	NM_001378452.1(ITPR1):c.1702A>G (p.Arg568Gly)	ITPR1	Pathogenic	criteria provided, single submitter
503525	NM_001378452.1(ITPR1):c.7352T>C (p.Leu2451Pro)	ITPR1	Pathogenic	criteria provided, single submitter
559630	NM_001378452.1(ITPR1):c.7793T>C (p.Ile2598Thr)	ITPR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
586057	NM_001378452.1(ITPR1):c.800C>G (p.Thr267Arg)	ITPR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
633506	NM_001378452.1(ITPR1):c.742_744del (p.Glu248del)	ITPR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1213800	NM_001378452.1(ITPR1):c.4691T>C (p.Leu1564Pro)	BRRIAR	Likely pathogenic	criteria provided, single submitter
1027414	NM_001378452.1(ITPR1):c.2843G>A (p.Gly948Glu)	ITPR1	Likely pathogenic	criteria provided, single submitter
1050804	NM_001378452.1(ITPR1):c.7798A>C (p.Thr2600Pro)	ITPR1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1285490	NM_001378452.1(ITPR1):c.1534G>A (p.Glu512Lys)	ITPR1	Likely pathogenic	criteria provided, single submitter
216945	NM_001378452.1(ITPR1):c.830G>T (p.Ser277Ile)	ITPR1	Likely pathogenic	criteria provided, single submitter
243076	NM_001378452.1(ITPR1):c.7784G>C (p.Gly2595Ala)	ITPR1	Likely pathogenic	criteria provided, single submitter
3377491	NM_001378452.1(ITPR1):c.7301C>T (p.Thr2434Ile)	ITPR1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
585154	NM_001378452.1(ITPR1):c.4333G>A (p.Val1445Met)	ITPR1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
915289	NM_001378452.1(ITPR1):c.1510A>G (p.Arg504Gly)	ITPR1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
981273	NM_001378452.1(ITPR1):c.1531A>G (p.Arg511Gly)	ITPR1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
39571	NM_001378452.1(ITPR1):c.4684G>A (p.Val1562Met)	BRRIAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1050806	NM_001378452.1(ITPR1):c.755C>T (p.Thr252Ile)	ITPR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1321595	NM_001378452.1(ITPR1):c.7474G>A (p.Gly2492Ser)	ITPR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1350168	NM_001378452.1(ITPR1):c.106C>T (p.Arg36Cys)	ITPR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1468074	NM_001378452.1(ITPR1):c.5006C>A (p.Thr1669Lys)	ITPR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1802278	NM_001378452.1(ITPR1):c.1813C>G (p.Leu605Val)	ITPR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3376847	NM_001378452.1(ITPR1):c.823G>A (p.Ala275Thr)	ITPR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345716	NM_001378452.1(ITPR1):c.2732C>T (p.Ala911Val)	ITPR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · Orphanet: 3 · 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
ITPR1	Definitive	Autosomal dominant	aniridia-cerebellar ataxia-intellectual disability syndrome	17

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ITPR1	Orphanet:1065	Aniridia-cerebellar ataxia-intellectual disability syndrome
ITPR1	Orphanet:208513	Spinocerebellar ataxia type 29
ITPR1	Orphanet:98769	Spinocerebellar ataxia type 15/16

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
ITPR1	HGNC:6180	ENSG00000150995	Q14643	Inositol 1,4,5-trisphosphate-gated calcium channel ITPR1	gencc,clinvar
BRRIAR	HGNC:59155			BHLHE40 and RIG-I regulating ITPR1 antisense RNA	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ITPR1	Inositol 1,4,5-trisphosphate-gated calcium channel ITPR1	Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER).

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
Ion channel	1	55.8×	0.036
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ITPR1	Ion channel	yes		InsP3_rcpt, RIH_dom, Ion_trans_dom
BRRIAR	Other/Unknown	no

Expression context

Cohort genes with no expression data: 1.

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	1

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	1
cauda epididymis	1
primary visual cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ITPR1	284	ubiquitous	marker	cauda epididymis, Brodmann (1909) area 23, primary visual cortex
BRRIAR

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITPR1	3,483
BRRIAR	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ITPR1	Q14643

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 51. 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
CLEC7A (Dectin-1) induces NFAT activation	1	1038.2×	0.008	ITPR1
Nitric oxide stimulates guanylate cyclase	1	815.7×	0.008	ITPR1
Elevation of cytosolic Ca2+ levels	1	713.8×	0.008	ITPR1
Platelet calcium homeostasis	1	713.8×	0.008	ITPR1
cGMP effects	1	713.8×	0.008	ITPR1
VEGFR2 mediated cell proliferation	1	571.0×	0.008	ITPR1
Effects of PIP2 hydrolysis	1	456.8×	0.008	ITPR1
Role of phospholipids in phagocytosis	1	456.8×	0.008	ITPR1
Anti-inflammatory response favouring Leishmania parasite infection	1	393.8×	0.008	ITPR1
Leishmania parasite growth and survival	1	393.8×	0.008	ITPR1
FCERI mediated Ca+2 mobilization	1	356.9×	0.008	ITPR1
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	1	356.9×	0.008	ITPR1
Signaling by the B Cell Receptor (BCR)	1	346.1×	0.008	ITPR1
G-protein mediated events	1	326.3×	0.008	ITPR1
DAG and IP3 signaling	1	317.2×	0.008	ITPR1
Beta-catenin independent WNT signaling	1	292.8×	0.008	ITPR1
FCGR3A-mediated IL10 synthesis	1	292.8×	0.008	ITPR1
Fcgamma receptor (FCGR) dependent phagocytosis	1	278.5×	0.008	ITPR1
Platelet homeostasis	1	278.5×	0.008	ITPR1
Fc epsilon receptor (FCERI) signaling	1	271.9×	0.008	ITPR1
Opioid Signalling	1	265.6×	0.008	ITPR1
PLC beta mediated events	1	265.6×	0.008	ITPR1
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1	265.6×	0.008	ITPR1
C-type lectin receptors (CLRs)	1	237.9×	0.009	ITPR1
Signaling by VEGF	1	219.6×	0.009	ITPR1
Regulation of insulin secretion	1	219.6×	0.009	ITPR1
Ion homeostasis	1	203.9×	0.009	ITPR1
Ca2+ pathway	1	178.4×	0.010	ITPR1
Integration of energy metabolism	1	175.7×	0.010	ITPR1
Leishmania infection	1	163.1×	0.010	ITPR1

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
release of sequestered calcium ion into cytosol by endoplasmic reticulum	1	8426.0×	0.002	ITPR1
voluntary musculoskeletal movement	1	2808.7×	0.002	ITPR1
phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway	1	2106.5×	0.002	ITPR1
epithelial fluid transport	1	2106.5×	0.002	ITPR1
negative regulation of calcium-mediated signaling	1	2106.5×	0.002	ITPR1
ligand-gated ion channel signaling pathway	1	1872.4×	0.002	ITPR1
calcium import into the mitochondrion	1	1203.7×	0.002	ITPR1
regulation of calcium-mediated signaling	1	1123.5×	0.002	ITPR1
endoplasmic reticulum calcium ion homeostasis	1	842.6×	0.003	ITPR1
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	1	481.5×	0.005	ITPR1
regulation of cytosolic calcium ion concentration	1	383.0×	0.005	ITPR1
release of sequestered calcium ion into cytosol	1	343.9×	0.005	ITPR1
positive regulation of insulin secretion	1	255.3×	0.006	ITPR1
regulation of autophagy	1	240.7×	0.006	ITPR1
protein homotetramerization	1	237.3×	0.006	ITPR1
post-embryonic development	1	205.5×	0.007	ITPR1
single fertilization	1	183.2×	0.007	ITPR1
calcium ion transport	1	181.2×	0.007	ITPR1
cell morphogenesis	1	157.5×	0.007	ITPR1
response to hypoxia	1	95.8×	0.011	ITPR1
positive regulation of apoptotic process	1	56.7×	0.018	ITPR1
signal transduction	1	16.1×	0.062	ITPR1

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
ITPR1	0	0
BRRIAR	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
ITPR1	13	Binding:12, Functional:1

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	1	ITPR1
E	Difficult family or no structure, no drug	1	BRRIAR

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)
ITPR1	13	—
BRRIAR	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT06840366	Not specified	COMPLETED	Motor Rehabilitation and Physical, Mental and Cognitive Health in Patients With Stroke