ATP13A2

Chr 1AR

ATPase cation transporting 13A2

Also known as: CLN12, HSA9947, KRPPD, PARK9, SPG78

This gene encodes a P5-type ATPase that transports inorganic cations and localizes to the lysosome membrane. Biallelic mutations cause Kufor-Rakeb syndrome (a juvenile-onset parkinsonism with pyramidal signs and dementia) and autosomal recessive spastic paraplegia 78. Mutations can cause disease through multiple mechanisms depending on the variant type, with the gene showing moderate constraint against loss-of-function variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.582 OMIM phenotypes
Clinical SummaryATP13A2
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Gene-Disease Validity (ClinGen)
Kufor-Rakeb syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.58LOEUF
pLI 0.000
Z-score 4.12
OE 0.42 (0.300.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.40Z-score
OE missense 0.85 (0.800.91)
624 obs / 730.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.42 (0.300.58)
00.351.4
Missense OE0.85 (0.800.91)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 24 / 57.8Missense obs/exp: 624 / 730.5Syn Z: -0.54
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateATP13A2-related Parkinson diseaseLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7326th %ile
GOF
0.76top 25%
LOF
0.2679th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ATP13A2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗