ATP13A4

Chr 3

ATPase 13A4

NCBI Gene: 84239 ENSG00000127249 UniProt: Q4VNC1 OMIM: 609556

Predicted to enable ATPase-coupled monoatomic cation transmembrane transporter activity and polyamine transmembrane transporter activity. Predicted to be involved in intracellular calcium ion homeostasis and polyamine transmembrane transport. Predicted to be located in early endosome membrane and recycling endosome membrane. Predicted to be active in endoplasmic reticulum membrane and late endosome membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.95

Clinical Summary— ATP13A4

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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

1 unique Pathogenic / Likely Pathogenic· 175 VUS of 234 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.000

Z-score 1.90

OE 0.75 (0.59–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.05Z-score

OE missense 0.99 (0.93–1.06)

636 obs / 639.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.75 (0.59–0.95)

0≤0.351.4

Missense OE?0.99 (0.93–1.06)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 49 / 65.6Missense obs/exp: 636 / 639.5Syn Z: -0.43

This gene — mechanism propensity

0.6841th %ile

GOF

0.76top 25%

LOF

0.2969th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

234 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS175

Likely Benign24

Benign11

Conflicting1

Pathogenic

175

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	1	0	1
Likely Pathogenic	0	0	0	0	0
VUS	1	173	1	0	175
Likely Benign	0	11	3	10	24
Benign	0	5	1	5	11
Conflicting	—				1
Total	1	189	6	15	212

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

View in ClinVar →

35 pathogenic / likely-pathogenic (of 40) ClinVar copy-number / structural variants overlap ATP13A4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →