parkinsonism due to ATP13A2 deficiency

Summary

parkinsonism due to ATP13A2 deficiency (MONDO:0017809) 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
• ClinVar variants: 1
• Phenotypes (HPO): 18
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

18 HPO clinical features (Orphanet curated; top 18 by frequency):

HPO ID	Term	Frequency
HP:0002063	Rigidity	Very frequent (80-99%)
HP:0001332	Dystonia	Frequent (30-79%)
HP:0001336	Myoclonus	Frequent (30-79%)
HP:0001337	Tremor	Frequent (30-79%)
HP:0002067	Bradykinesia	Frequent (30-79%)
HP:0002172	Postural instability	Frequent (30-79%)
HP:0002506	Diffuse cerebral atrophy	Frequent (30-79%)
HP:0002548	Parkinsonism with favorable response to dopaminergic medication	Frequent (30-79%)
HP:0003487	Babinski sign	Frequent (30-79%)
HP:0025331	Upgaze palsy	Frequent (30-79%)
HP:0100543	Cognitive impairment	Frequent (30-79%)
HP:0001260	Dysarthria	Occasional (5-29%)
HP:0001288	Gait disturbance	Occasional (5-29%)
HP:0001324	Muscle weakness	Occasional (5-29%)
HP:0002339	Abnormal caudate nucleus morphology	Occasional (5-29%)
HP:0012378	Fatigue	Occasional (5-29%)
HP:0000716	Depression	Very rare (<1-4%)
HP:0002174	Postural tremor	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	parkinsonism due to ATP13A2 deficiency
Mondo ID	MONDO:0017809
Orphanet	314632
SNOMED CT	789657008
UMLS	C5230619
MedGen	1687881
GARD	0017427
Is cancer (heuristic)	no

Also known as: CLN12 disease

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record.

Disease family

Classification path: disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › basal ganglia disorder › parkinsonian disorder › Parkinson disease › young-onset Parkinson disease › juvenile-onset Parkinson disease › Kufor-Rakeb syndrome › parkinsonism due to ATP13A2 deficiency

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

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
128469	NM_022089.4(ATP13A2):c.2836A>T (p.Ile946Phe)	ATP13A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · 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
ATP13A2	Supportive	Autosomal recessive	parkinsonism due to ATP13A2 deficiency	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATP13A2	Orphanet:306674	Kufor-Rakeb syndrome
ATP13A2	Orphanet:314632	CLN12 disease
ATP13A2	Orphanet:513436	Autosomal recessive spastic paraplegia type 78

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
ATP13A2	HGNC:30213	ENSG00000159363	Q9NQ11	Polyamine-transporting ATPase 13A2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATP13A2	Polyamine-transporting ATPase 13A2	ATPase which acts as a lysosomal polyamine exporter with high affinity for spermine.

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)
ATP13A2	Transcription factor	no		P_typ_ATPase, P-type_TPase_V, ATPase_P-typ_transduc_dom_A_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
prefrontal cortex	1
right frontal lobe	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATP13A2	249	ubiquitous	marker	right frontal lobe, right hemisphere of cerebellum, prefrontal cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP13A2	2,267

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATP13A2	Q9NQ11	25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Ion transport by P-type ATPases	1	207.6×	0.014	ATP13A2
Ion channel transport	1	96.0×	0.016	ATP13A2
Transport of small molecules	1	25.1×	0.040	ATP13A2

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
spermine transmembrane transport	1	16852.0×	0.001	ATP13A2
extracellular exosome biogenesis	1	8426.0×	0.001	ATP13A2
regulation of autophagosome size	1	5617.3×	0.001	ATP13A2
regulation of lysosomal protein catabolic process	1	5617.3×	0.001	ATP13A2
polyamine transmembrane transport	1	4213.0×	0.001	ATP13A2
regulation of chaperone-mediated autophagy	1	3370.4×	0.001	ATP13A2
autophagosome organization	1	3370.4×	0.001	ATP13A2
negative regulation of lysosomal protein catabolic process	1	3370.4×	0.001	ATP13A2
regulation of intracellular protein transport	1	2808.7×	0.001	ATP13A2
regulation of autophagy of mitochondrion	1	2808.7×	0.001	ATP13A2
cellular response to manganese ion	1	2407.4×	0.001	ATP13A2
regulation of protein localization to nucleus	1	2106.5×	0.001	ATP13A2
autophagosome-lysosome fusion	1	1203.7×	0.002	ATP13A2
intracellular monoatomic cation homeostasis	1	1123.5×	0.002	ATP13A2
positive regulation of exosomal secretion	1	1123.5×	0.002	ATP13A2
protein localization to lysosome	1	1053.2×	0.002	ATP13A2
regulation of mitochondrion organization	1	842.6×	0.002	ATP13A2
lysosomal transport	1	702.2×	0.002	ATP13A2
regulation of neuron apoptotic process	1	702.2×	0.002	ATP13A2
cellular response to zinc ion	1	674.1×	0.002	ATP13A2
intracellular zinc ion homeostasis	1	481.5×	0.003	ATP13A2
positive regulation of protein secretion	1	343.9×	0.004	ATP13A2
lipid homeostasis	1	337.0×	0.004	ATP13A2
regulation of macroautophagy	1	295.6×	0.004	ATP13A2
intracellular iron ion homeostasis	1	244.2×	0.005	ATP13A2
monoatomic ion transmembrane transport	1	208.1×	0.006	ATP13A2
cellular response to oxidative stress	1	154.6×	0.007	ATP13A2
intracellular calcium ion homeostasis	1	145.3×	0.007	ATP13A2
autophagy	1	110.1×	0.009	ATP13A2
positive regulation of gene expression	1	38.7×	0.026	ATP13A2

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
ATP13A2	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	ATP13A2

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)
ATP13A2	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
NCT04613089	Not specified	RECRUITING	Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database