ATP13A2

Chr 1AR

ATPase cation transporting 13A2

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

NCBI Gene: 23400ENSG00000159363UniProt: Q9NQ11

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]

Primary Disease Associations & Inheritance

Kufor-Rakeb syndromeMIM #606693
AR
Spastic paraplegia 78, autosomal recessiveMIM #617225
AR
571
ClinVar variants
50
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— ATP13A2
🧬
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.
📋
ClinVar Variants
50 Pathogenic / Likely Pathogenic· 170 VUS of 571 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.40Z-score
OE missense 0.85 (0.80–0.91)
624 obs / 730.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.42 (0.30–0.58)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.80–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.04
0≤1.21.6
LoF obs/exp: 24 / 57.8Missense obs/exp: 624 / 730.5Syn Z: -0.54

ClinVar Variant Classifications

571 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic20
VUS170
Likely Benign305
Benign21
Conflicting25
30
Pathogenic
20
Likely Pathogenic
170
VUS
305
Likely Benign
21
Benign
25
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
0
14
0
30
Likely Pathogenic
14
0
6
0
20
VUS
1
150
15
4
170
Likely Benign
0
19
127
159
305
Benign
0
0
21
0
21
Conflicting
—25
Total31169183163571

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

View 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.

Gene2Phenotype Curations

ATP13A2-related Parkinson disease

moderate
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
ATPase 13A2; ATP13A2
MIM #610513 · *

Kufor-Rakeb syndrome

MIM #606693

Molecular basis of disorder known

Autosomal recessive

Spastic paraplegia 78, autosomal recessive

MIM #617225

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — ATP13A2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Neuronal Ceroid LipofuscinosisBatten DiseaseCLN1 Disease

Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database

RECRUITING
NCT04613089Universitätsklinikum Hamburg-EppendorfStarted 2020-04-08
Natural History

External Resources

Links to major genomics databases and tools