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…

Primary Disease Associations & Inheritance

Pulmonary hypertension, primary, 5MIM #265400

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · pulmonary arterial hypertension · SD · ClinGen 2021

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.22

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

📖

GeneReview available — ATP13A3

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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

Background carrier burden — how many people carry a rare variant somewhere in ATP13A3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 54

1,270 rare PASS variants

Rare truncating (LoF)

1 in 2,100

136 rare PASS variants

Rare synonymous (reference)

1 in 95

515 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ATP13A3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 79	1 in 2,600
South Asian	~43k	1 in 41	1 in 1,300
Remaining (unassigned)	~30k	1 in 42	1 in 2,500
European (Finnish)	~27k	1 in 190	1 in 2,800
Admixed American	~22k	1 in 46	1 in 1,200
African / African American	~21k	1 in 55	1 in 1,500
East Asian	~20k	1 in 63	1 in 1,600
Ashkenazi Jewish	~13k	1 in 260	1 in 690
Middle Eastern	~2,884	1 in 67	≈ 1 in 2,800

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 26 of 32 coding exons well covered in gnomAD exomes; exons 6, 8, 17, 28, 31, 32 marginal. Genomes: all 32.? see exons ↓