ATP11A

Chr 13AD

ATPase phospholipid transporting 11A

Also known as: ATPIH, ATPIS, AUNA2, DFNA84, HLD24

NCBI Gene: 23250 ENSG00000068650 UniProt: P98196 OMIM: 605868

This protein is a P4-ATPase flippase that transports phospholipids from the outer to inner leaflet of cell membranes and contributes to muscle cell development. Autosomal dominant mutations cause hearing loss (deafness or auditory neuropathy) and possibly hypomyelinating leukodystrophy. The gene is highly constrained against loss-of-function variants (LOEUF 0.467), suggesting intolerance to protein disruption.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is an integral membrane ATPase. The encoded protein is probably phosphorylated in its intermediate state and likely drives the transport of ions such as calcium across membranes. [provided by RefSeq, Apr 2022]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Auditory neuropathy, autosomal dominant 2MIM #620384

?Leukodystrophy, hypomyelinating, 24MIM #619851

Deafness, autosomal dominant 84MIM #619810

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · autosomal dominant nonsyndromic hearing loss · AD · ClinGen 2025

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

0.47

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.47LOEUF

pLI 0.000

Z-score 5.19

OE 0.33 (0.24–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.37Z-score

OE missense 0.85 (0.80–0.91)

592 obs / 693.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.24–0.47)

0≤0.351.4

Missense OE?0.85 (0.80–0.91)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 23 / 69.8Missense obs/exp: 592 / 693.3Syn Z: -1.13

Background carrier burden — how many people carry a rare variant somewhere in ATP11A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 35

1,604 rare PASS variants

Rare truncating (LoF)

1 in 330

215 rare PASS variants

Rare synonymous (reference)

1 in 40

727 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ATP11A. 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 50	1 in 1,100
South Asian	~43k	1 in 31	1 in 1,200
Remaining (unassigned)	~30k	1 in 29	1 in 340
European (Finnish)	~27k	1 in 67	1 in 1,300
Admixed American	~22k	1 in 29	1 in 560
African / African American	~21k	1 in 32	1 in 710
East Asian	~20k	1 in 32	1 in 1,200
Ashkenazi Jewish	~13k	1 in 86	1 in 500
Middle Eastern	~2,884	1 in 29	≈ 1 in 1,200

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): 25 of 29 coding exons well covered in gnomAD exomes; exons 1, 2, 3, 16 marginal. Genomes: all 29.? see exons ↓