X-linked non progressive cerebellar ataxia

Summary

X-linked non progressive cerebellar ataxia (MONDO:0010404) is a disease with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 16
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0002470	Nonprogressive cerebellar ataxia	Very frequent (80-99%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0001152	Saccadic smooth pursuit	Frequent (30-79%)
HP:0001270	Motor delay	Frequent (30-79%)
HP:0001320	Cerebellar vermis hypoplasia	Frequent (30-79%)
HP:0001321	Cerebellar hypoplasia	Frequent (30-79%)
HP:0002078	Truncal ataxia	Frequent (30-79%)
HP:0002080	Intention tremor	Frequent (30-79%)
HP:0002312	Clumsiness	Frequent (30-79%)
HP:0002317	Unsteady gait	Frequent (30-79%)
HP:0002345	Action tremor	Frequent (30-79%)
HP:0002359	Frequent falls	Frequent (30-79%)
HP:0002464	Spastic dysarthria	Frequent (30-79%)
HP:0008935	Generalized neonatal hypotonia	Frequent (30-79%)
HP:0001249	Intellectual disability	Excluded (0%)
HP:0003487	Babinski sign	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	X-linked non progressive cerebellar ataxia
Mondo ID	MONDO:0010404
MeSH	C567478
OMIM	300703
Orphanet	314978
DOID	DOID:0111833
SNOMED CT	766818009
UMLS	C2678048
MedGen	394718
GARD	0017439
Is cancer (heuristic)	no

Also known as: SCAX5 · spinocerebellar ataxia, X-linked 5 · spinocerebellar ataxia, X-linked 5, X-linked recessive · X-linked spinocerebellar ataxia type 5

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › X-linked disease › X-linked cerebellar ataxia › X-linked non progressive cerebellar ataxia

Related subtypes (8): ataxia - deafness - intellectual disability syndrome, fragile X-associated tremor/ataxia syndrome, X-linked sideroblastic anemia with ataxia, X-linked spinocerebellar ataxia type 3, X-linked spinocerebellar ataxia type 4, X-linked progressive cerebellar ataxia, spinocerebellar ataxia, X-linked 2, X-linked intellectual disability-ataxia-apraxia syndrome

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
ATP2B3	Strong	X-linked	X-linked progressive cerebellar ataxia	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATP2B3	Orphanet:314978	X-linked non progressive cerebellar ataxia

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
ATP2B3	HGNC:816	ENSG00000067842	Q16720	Plasma membrane calcium-transporting ATPase 3	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATP2B3	Plasma membrane calcium-transporting ATPase 3	ATP-driven Ca(2+) ion pump involved in the maintenance of basal intracellular Ca(2+) levels at the presynaptic terminals.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATP2B3	Transcription factor	no	7.2.2.10	P_typ_ATPase, ATPase_P-typ_cation-transptr_N, ATPase_P-typ_cation-transptr_C

Expression context

Cohort genes with no expression data: 0.

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
Brodmann (1909) area 23	1
endothelial cell	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATP2B3	145	tissue_specific	yes	endothelial cell, Brodmann (1909) area 23, middle temporal gyrus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP2B3	3,203

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATP2B3	Q16720	74.57

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Reduction of cytosolic Ca++ levels	1	951.7×	0.007	ATP2B3
Platelet calcium homeostasis	1	713.8×	0.007	ATP2B3
Platelet homeostasis	1	278.5×	0.010	ATP2B3
Ion transport by P-type ATPases	1	207.6×	0.010	ATP2B3
Ion homeostasis	1	203.9×	0.010	ATP2B3
Cardiac conduction	1	108.8×	0.015	ATP2B3
Ion channel transport	1	96.0×	0.015	ATP2B3
Muscle contraction	1	77.2×	0.016	ATP2B3
Hemostasis	1	36.0×	0.031	ATP2B3
Transport of small molecules	1	25.1×	0.040	ATP2B3

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
calcium ion export across plasma membrane	1	2808.7×	0.001	ATP2B3
regulation of cardiac conduction	1	842.6×	0.002	ATP2B3
regulation of cytosolic calcium ion concentration	1	383.0×	0.003	ATP2B3
monoatomic ion transmembrane transport	1	208.1×	0.005	ATP2B3

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
ATP2B3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ATP2B3	7.2.2.10	P-type Ca2+ transporter

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	ATP2B3

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)
ATP2B3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

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