Cayman type cerebellar ataxia

Summary

Cayman type cerebellar ataxia (MONDO:0011025) is a disease caused by ATCAY (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: ATCAY (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 139
• Phenotypes (HPO): 11
• Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

11 HPO clinical features (Orphanet curated; top 11 by frequency):

HPO ID	Term	Frequency
HP:0002470	Nonprogressive cerebellar ataxia	Very frequent (80-99%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0001260	Dysarthria	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001290	Generalized hypotonia	Frequent (30-79%)
HP:0001321	Cerebellar hypoplasia	Frequent (30-79%)
HP:0002066	Gait ataxia	Frequent (30-79%)
HP:0002078	Truncal ataxia	Frequent (30-79%)
HP:0002080	Intention tremor	Frequent (30-79%)
HP:0002136	Broad-based gait	Frequent (30-79%)
HP:0000479	Abnormal retinal morphology	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Cayman type cerebellar ataxia
Mondo ID	MONDO:0011025
MeSH	C563363
OMIM	601238
Orphanet	94122
DOID	DOID:0060694
SNOMED CT	717332007
UMLS	C1832585
MedGen	331319
GARD	0016836
Is cancer (heuristic)	no

Also known as: ataxia, cerebellar, Cayman type · ATCAY · Cayman ataxia · Cayman type cerebellar ataxia · cerebellar ataxia, Cayman type

Data availability: 139 ClinVar variants · 4 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 recessive disease › autosomal recessive cerebellar ataxia › autosomal recessive congenital cerebellar ataxia › Cayman type cerebellar ataxia

Related subtypes (6): autosomal recessive spinocerebellar ataxia 2, cerebellar ataxia, intellectual disability, and dysequilibrium, autosomal recessive spinocerebellar ataxia 17, Joubert syndrome and related disorders, CAMOS syndrome, congenital cerebellar ataxia due to RNU12 mutation

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

139 retrieved; paginated sample, class counts are floors:

85 uncertain significance, 28 benign, 10 likely benign, 7 conflicting classifications of pathogenicity, 6 benign/likely benign, 3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2491	NM_033064.5(ATCAY):c.[903C>G;965+3G>T]		Pathogenic	no assertion criteria provided
1319958	NM_033064.5(ATCAY):c.602_608del (p.Asp201fs)	ATCAY	Pathogenic	no assertion criteria provided
4293711	NM_033064.5(ATCAY):c.556G>T (p.Glu186Ter)	ATCAY	Pathogenic	criteria provided, single submitter
328984	NM_033064.5(ATCAY):c.36C>T (p.Asn12=)	ATCAY	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
329118	NM_033064.5(ATCAY):c.162C>T (p.Asn54=)	ATCAY	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
329141	NM_033064.5(ATCAY):c.405G>A (p.Ala135=)	ATCAY	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
329150	NM_033064.5(ATCAY):c.717G>A (p.Thr239=)	ATCAY	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
710642	NM_033064.5(ATCAY):c.1106+10A>T	ATCAY	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
715321	NM_033064.5(ATCAY):c.98G>A (p.Gly33Glu)	ATCAY	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
789346	NM_033064.5(ATCAY):c.1053G>A (p.Glu351=)	ATCAY	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029011	NM_033064.5(ATCAY):c.370G>A (p.Val124Met)	ATCAY	Uncertain significance	criteria provided, multiple submitters, no conflicts
2412765	NM_033064.5(ATCAY):c.552C>G (p.Tyr184Ter)	ATCAY	Uncertain significance	criteria provided, single submitter
2439308	NM_033064.5(ATCAY):c.-41-1022G>A	ATCAY	Uncertain significance	criteria provided, single submitter
2439309	NM_033064.5(ATCAY):c.1043A>G (p.Glu348Gly)	ATCAY	Uncertain significance	criteria provided, single submitter
328983	NM_033064.5(ATCAY):c.-198C>G	ATCAY	Uncertain significance	criteria provided, single submitter
329143	NM_033064.5(ATCAY):c.478G>A (p.Gly160Arg)	ATCAY	Uncertain significance	criteria provided, single submitter
329146	NM_033064.5(ATCAY):c.555C>A (p.Gly185=)	ATCAY	Uncertain significance	criteria provided, single submitter
329147	NM_033064.5(ATCAY):c.568G>A (p.Ala190Thr)	ATCAY	Uncertain significance	criteria provided, single submitter
329154	NM_033064.5(ATCAY):c.*143G>A	ATCAY	Uncertain significance	criteria provided, single submitter
329157	NM_033064.5(ATCAY):c.*266C>T	ATCAY	Uncertain significance	criteria provided, single submitter
329159	NM_033064.5(ATCAY):c.*391C>A	ATCAY	Uncertain significance	criteria provided, single submitter
329160	NM_033064.5(ATCAY):c.*441G>A	ATCAY	Uncertain significance	criteria provided, single submitter
329163	NM_033064.5(ATCAY):c.*496C>A	ATCAY	Uncertain significance	criteria provided, single submitter
329164	NM_033064.5(ATCAY):c.*681A>G	ATCAY	Uncertain significance	criteria provided, single submitter
329165	NM_033064.5(ATCAY):c.*687C>A	ATCAY	Uncertain significance	criteria provided, single submitter
329166	NM_033064.5(ATCAY):c.*728T>C	ATCAY	Uncertain significance	criteria provided, single submitter
329167	NM_033064.5(ATCAY):c.*740G>A	ATCAY	Uncertain significance	criteria provided, single submitter
329169	NM_033064.5(ATCAY):c.*813G>C	ATCAY	Uncertain significance	criteria provided, single submitter
329171	NM_033064.5(ATCAY):c.*939G>A	ATCAY	Uncertain significance	criteria provided, single submitter
329174	NM_033064.5(ATCAY):c.*1167G>A	ATCAY	Uncertain significance	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
ATCAY	Strong	Autosomal recessive	Cayman type cerebellar ataxia	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATCAY	Orphanet:94122	Cerebellar ataxia, Cayman type

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
ATCAY	HGNC:779	ENSG00000167654	Q86WG3	Caytaxin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATCAY	Caytaxin	Functions in the development of neural tissues, particularly the postnatal maturation of the cerebellar cortex.

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)
ATCAY	Other/Unknown	no		CRAL-TRIO_dom, Bcl2-/adenovirus-E1B, CRAL-TRIO_dom_sf

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
Brodmann (1909) area 23	1
cortical plate	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATCAY	150	broad	marker	middle temporal gyrus, cortical plate, Brodmann (1909) area 23

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATCAY	531

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATCAY	Q86WG3	70.68

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
obsolete negative regulation of glutamate metabolic process	1	16852.0×	3e-04	ATCAY
mitochondrion distribution	1	2106.5×	0.001	ATCAY
regulation of protein localization	1	205.5×	0.008	ATCAY
neuron projection development	1	122.1×	0.010	ATCAY
apoptotic process	1	28.7×	0.035	ATCAY

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
ATCAY	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	ATCAY

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)
ATCAY	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