ATP11A

Chr 13AD

ATPase phospholipid transporting 11A

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 0.473 OMIM phenotypes
Clinical SummaryATP11A
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Gene-Disease Validity (ClinGen)
autosomal dominant nonsyndromic hearing loss · ADModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.47LOEUF
pLI 0.000
Z-score 5.19
OE 0.33 (0.240.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.37Z-score
OE missense 0.85 (0.800.91)
592 obs / 693.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.240.47)
00.351.4
Missense OE0.85 (0.800.91)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 23 / 69.8Missense obs/exp: 592 / 693.3Syn Z: -1.13
DN
0.74top 25%
GOF
0.78top 25%
LOF
0.2091th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, dominant-negative and loss-of-function). 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
LOF1 literature citation · LOEUF 0.47

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.

Literature Evidence

LOFHaploinsufficiency of ATP11A, the phospholipid flippase that specially transports phosphatidylserine (PS) and phosphatidylethanolamine (PE), could leave cells with PS/PE at the extracellular side vulnerable to phagocytic degradation.PMID:35278131

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ATP11A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC