ATP13A3

Chr 3AR

ATPase 13A3

Also known as: AFURS1, PPH5

NCBI Gene: 79572 ENSG00000133657 UniProt: Q9H7F0 OMIM: 610232

ATP13A3 is a member of the P-type ATPase family of proteins that transport a variety of cations across membranes. Other P-type ATPases include ATP7B (MIM 606882) and ATP7A (MIM 300011).[supplied by OMIM, Aug 2008]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.221 OMIM phenotype

Clinical Summary— ATP13A3

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Gene-Disease Validity (ClinGen)

pulmonary arterial hypertension · SDDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

8 unique Pathogenic / Likely Pathogenic· 149 VUS of 314 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ATP13A3

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.22LOEUF

pLI 1.000

Z-score 6.59

OE 0.12 (0.07–0.22)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.01Z-score

OE missense 0.67 (0.62–0.72)

444 obs / 662.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.12 (0.07–0.22)

0≤0.351.4

Missense OE?0.67 (0.62–0.72)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 8 / 65.5Missense obs/exp: 444 / 662.3Syn Z: -0.14

This gene — mechanism propensity

0.4983th %ile

GOF

0.6736th %ile

LOF

0.52top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOF75% of P/LP variants are LoF · LOEUF 0.22

GOFprediction 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

314 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic2

VUS149

Likely Benign69

Benign51

Conflicting4

Pathogenic

Likely Pathogenic

149

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	6	0	0	0	6
Likely Pathogenic	0	2	0	0	2
VUS	1	144	4	0	149
Likely Benign	0	8	26	35	69
Benign	0	4	40	7	51
Conflicting	—				4
Total	7	158	70	42	281

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

View in ClinVar →

39 pathogenic / likely-pathogenic (of 47) ClinVar copy-number / structural variants overlap ATP13A3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →