ATP13A2

Chr 1AR

ATPase cation transporting 13A2

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

NCBI Gene: 23400 ENSG00000159363 UniProt: Q9NQ11 OMIM: 610513

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the P5 subfamily of ATPases which transports inorganic cations as well as other substrates. Mutations in this gene are associated with Kufor-Rakeb syndrome (KRS), also referred to as Parkinson disease 9. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.582 OMIM phenotypes

Clinical Summary— ATP13A2

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Gene-Disease Validity (ClinGen)

Kufor-Rakeb syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

96 unique Pathogenic / Likely Pathogenic· 487 VUS of 1263 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ATP13A2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.58LOEUF

pLI 0.000

Z-score 4.12

OE 0.42 (0.30–0.58)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.40Z-score

OE missense 0.85 (0.80–0.91)

624 obs / 730.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.42 (0.30–0.58)

0≤0.351.4

Missense OE?0.85 (0.80–0.91)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 24 / 57.8Missense obs/exp: 624 / 730.5Syn Z: -0.54

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateATP13A2-related Parkinson diseaseLOFAR

This gene — mechanism propensity

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

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

1263 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic54

Likely Pathogenic42

VUS487

Likely Benign510

Benign36

Conflicting105

Pathogenic

Likely Pathogenic

487

VUS

510

Likely Benign

Benign

105

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	47	4	3	0	54
Likely Pathogenic	39	2	1	0	42
VUS	8	432	33	14	487
Likely Benign	0	37	214	259	510
Benign	0	2	27	7	36
Conflicting	—				105
Total	94	477	278	280	1,234

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

20 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap ATP13A2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →