Autosomal recessive spastic paraplegia type 78

Summary

Autosomal recessive spastic paraplegia type 78 (MONDO:0014975) is a disease caused by ATP13A2 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ATP13A2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 972
• Phenotypes (HPO): 28

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		7	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

28 HPO clinical features (Orphanet curated; top 28 by frequency):

HPO ID	Term	Frequency
HP:0000486	Strabismus	Very frequent (80-99%)
HP:0001260	Dysarthria	Very frequent (80-99%)
HP:0001272	Cerebellar atrophy	Very frequent (80-99%)
HP:0001288	Gait disturbance	Very frequent (80-99%)
HP:0001347	Hyperreflexia	Very frequent (80-99%)
HP:0002073	Progressive cerebellar ataxia	Very frequent (80-99%)
HP:0002120	Cerebral cortical atrophy	Very frequent (80-99%)
HP:0003477	Peripheral axonal neuropathy	Very frequent (80-99%)
HP:0003482	EMG: axonal abnormality	Very frequent (80-99%)
HP:0003487	Babinski sign	Very frequent (80-99%)
HP:0007020	Progressive spastic paraplegia	Very frequent (80-99%)
HP:0007240	Progressive gait ataxia	Very frequent (80-99%)
HP:0100543	Cognitive impairment	Very frequent (80-99%)
HP:0000011	Neurogenic bladder	Frequent (30-79%)
HP:0000605	Supranuclear gaze palsy	Frequent (30-79%)
HP:0000666	Horizontal nystagmus	Frequent (30-79%)
HP:0001332	Dystonia	Frequent (30-79%)
HP:0001761	Pes cavus	Frequent (30-79%)
HP:0002079	Hypoplasia of the corpus callosum	Frequent (30-79%)
HP:0002478	Progressive spastic quadriplegia	Frequent (30-79%)
HP:0002518	Abnormal periventricular white matter morphology	Frequent (30-79%)
HP:0003390	Sensory axonal neuropathy	Frequent (30-79%)
HP:0007256	Abnormal pyramidal sign	Frequent (30-79%)
HP:0003202	Skeletal muscle atrophy	Excluded (0%)
HP:0000317	Facial myokymia	Very rare (<1-4%)
HP:0000726	Dementia	Very rare (<1-4%)
HP:0000738	Hallucinations	Very rare (<1-4%)
HP:0007153	Progressive extrapyramidal movement disorder	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive spastic paraplegia type 78
Mondo ID	MONDO:0014975
OMIM	617225
Orphanet	513436
DOID	DOID:0112348
UMLS	C5567893
MedGen	1799316
GARD	0017952
Is cancer (heuristic)	no

Also known as: ATP13A2 hereditary spastic paraplegia · hereditary spastic paraplegia caused by mutation in ATP13A2 · spastic paraplegia 78, autosomal recessive · spastic paraplegia 78, autosomal recessive; SPG78 · SPG78

Data availability: 972 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 spastic paraplegia type 78

Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, acromesomelic dysplasia 2B, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, hydrocephalus, nonsyndromic, autosomal recessive 1, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Bjornstad syndrome, Laron syndrome, autosomal recessive polycystic kidney disease, autosomal recessive inherited pseudoxanthoma elasticum, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, short-rib thoracic dysplasia 9 with or without polydactyly, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, congenital prothrombin deficiency, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, Nestor-Guillermo progeria syndrome, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, UV-sensitive syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, autosomal recessive hypohidrotic ectodermal dysplasia, Warburg micro syndrome, autosomal recessive primary microcephaly, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, de Barsy syndrome, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, autosomal recessive distal renal tubular acidosis, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, nephronophthisis, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, hearing loss, autosomal recessive, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, severe combined immunodeficiency due to CARMIL2 deficiency, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB2, autosomal recessive, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy

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

600 retrieved; paginated sample, class counts are floors:

251 likely benign, 237 uncertain significance, 50 conflicting classifications of pathogenicity, 25 pathogenic, 14 benign, 10 benign/likely benign, 9 likely pathogenic, 4 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1029840	NM_022089.4(ATP13A2):c.2529+1G>A	ATP13A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075283	NM_022089.4(ATP13A2):c.3136G>T (p.Glu1046Ter)	ATP13A2	Pathogenic	criteria provided, single submitter
1075284	NM_022089.4(ATP13A2):c.2146del (p.Asp715_Leu716insTer)	ATP13A2	Pathogenic	criteria provided, single submitter
1176183	NM_022089.4(ATP13A2):c.2116C>T (p.Gln706Ter)	ATP13A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1219	NM_022089.4(ATP13A2):c.1306+5G>A	ATP13A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1221	NM_022089.4(ATP13A2):c.1510G>C (p.Gly504Arg)	ATP13A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1333442	NM_022089.4(ATP13A2):c.688C>T (p.Gln230Ter)	ATP13A2	Pathogenic	criteria provided, single submitter
1385899	NM_022089.4(ATP13A2):c.1113del (p.His372fs)	ATP13A2	Pathogenic	criteria provided, single submitter
1442231	NM_022089.4(ATP13A2):c.619C>T (p.Gln207Ter)	ATP13A2	Pathogenic	criteria provided, single submitter
1456750	NC_000001.10:g.(?17316166)(17332293_?)del	ATP13A2	Pathogenic	criteria provided, single submitter
1458906	NC_000001.10:g.(?17330807)(17332293_?)del	ATP13A2	Pathogenic	criteria provided, single submitter
1751269	NM_022089.4(ATP13A2):c.604del (p.His202fs)	ATP13A2	Pathogenic	criteria provided, multiple submitters, no conflicts
1810422	NM_022089.4(ATP13A2):c.1045_1046del (p.Ser349fs)	ATP13A2	Pathogenic	criteria provided, single submitter
1968613	NM_022089.4(ATP13A2):c.3153dup (p.Ser1052fs)	ATP13A2	Pathogenic	criteria provided, single submitter
1996186	NM_022089.4(ATP13A2):c.2113C>T (p.Gln705Ter)	ATP13A2	Pathogenic	criteria provided, single submitter
1999337	NM_022089.4(ATP13A2):c.1825G>T (p.Glu609Ter)	ATP13A2	Pathogenic	criteria provided, single submitter
2013159	NM_022089.4(ATP13A2):c.1296dup (p.Ser433fs)	ATP13A2	Pathogenic	criteria provided, single submitter
2021882	NM_022089.4(ATP13A2):c.965del (p.Gln322fs)	ATP13A2	Pathogenic	criteria provided, single submitter
2022009	NM_022089.4(ATP13A2):c.2587del (p.Val863fs)	ATP13A2	Pathogenic	criteria provided, single submitter
2039313	NM_022089.4(ATP13A2):c.572dup (p.Arg192fs)	ATP13A2	Pathogenic	criteria provided, single submitter
2046647	NM_022089.4(ATP13A2):c.774G>A (p.Trp258Ter)	ATP13A2	Pathogenic	criteria provided, multiple submitters, no conflicts
2064277	NM_022089.4(ATP13A2):c.533_536dup (p.Gln179fs)	ATP13A2	Pathogenic	criteria provided, single submitter
2151865	NM_022089.4(ATP13A2):c.217dup (p.Val73fs)	ATP13A2	Pathogenic	criteria provided, single submitter
2179757	NM_022089.4(ATP13A2):c.1378del (p.Arg460fs)	ATP13A2	Pathogenic	criteria provided, single submitter
2419737	NM_022089.4(ATP13A2):c.213G>A (p.Trp71Ter)	ATP13A2	Pathogenic	criteria provided, single submitter
2629777	NM_022089.4(ATP13A2):c.1033_1034del (p.Leu345fs)	ATP13A2	Pathogenic	criteria provided, multiple submitters, no conflicts
2663862	NM_022089.4(ATP13A2):c.2097del (p.Ser700fs)	ATP13A2	Pathogenic	criteria provided, multiple submitters, no conflicts
2923611	NM_022089.4(ATP13A2):c.1932del (p.Ala646fs)	ATP13A2	Pathogenic	criteria provided, single submitter
2931003	NM_022089.4(ATP13A2):c.217del (p.Val73fs)	ATP13A2	Pathogenic	criteria provided, single submitter
1031329	NM_022089.4(ATP13A2):c.3151_3152del (p.Phe1051fs)	ATP13A2	Likely pathogenic	criteria provided, single submitter

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	Strong	Autosomal recessive	autosomal recessive spastic paraplegia type 78	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: 0.