ATP11A

Chr 13AD

ATPase phospholipid transporting 11A

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

NCBI Gene: 23250ENSG00000068650UniProt: P98196

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]

Primary Disease Associations & Inheritance

?Auditory neuropathy, autosomal dominant 2MIM #620384
AD
?Leukodystrophy, hypomyelinating, 24MIM #619851
AD
Deafness, autosomal dominant 84MIM #619810
AD
403
ClinVar variants
125
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ATP11A
🧬
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.
📋
ClinVar Variants
125 Pathogenic / Likely Pathogenic· 211 VUS of 403 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.37Z-score
OE missense 0.85 (0.80–0.91)
592 obs / 693.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.33 (0.24–0.47)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.80–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.08
0≤1.21.6
LoF obs/exp: 23 / 69.8Missense obs/exp: 592 / 693.3Syn Z: -1.13

ClinVar Variant Classifications

403 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic121
Likely Pathogenic4
VUS211
Likely Benign42
Benign19
Conflicting6
121
Pathogenic
4
Likely Pathogenic
211
VUS
42
Likely Benign
19
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
2
117
0
121
Likely Pathogenic
1
0
3
0
4
VUS
1
193
17
0
211
Likely Benign
1
16
5
20
42
Benign
0
3
3
13
19
Conflicting
—6
Total521414533403

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Auditory neuropathy, autosomal dominant 2

MIM #620384

Molecular basis of disorder known

Autosomal dominant

?Leukodystrophy, hypomyelinating, 24

MIM #619851

Molecular basis of disorder known

Autosomal dominant

Deafness, autosomal dominant 84

MIM #619810

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A mutation in ATP11A causes autosomal-dominant auditory neuropathy type 2.
Chepurwar S et al.·Hum Mol Genet
2023
De novo heterozygous missense variants in ATP11A are associated with refractory focal epilepsy.
Ye ZL et al.·J Med Genet
2025
Autosomal dominant non-syndromic hearing loss maps to DFNA33 (13q34) and co-segregates with splice and frameshift variants in ATP11A, a phospholipid flippase gene.
Pater JA et al.·Hum Genet
2022
Substrates of P4-ATPases: beyond aminophospholipids (phosphatidylserine and phosphatidylethanolamine).
Shin HW et al.·FASEB J
2019Review
In Vivo Genome-Wide PGR Binding in Pregnant Human Myometrium Identifies Potential Regulators of Labor.
Dotts AJ et al.·Reprod Sci
2023
Association of a Single Nucleotide Variant in TERT with Airway Disease in Japanese Rheumatoid Arthritis Patients.
Higuchi T et al.·Genes (Basel)
2023Cohort
DNA Methylation at ATP11A cg11702988 Is a Biomarker of Lung Disease Severity in Cystic Fibrosis: A Longitudinal Study.
Pineau F et al.·Genes (Basel)
2021Natural history
Identification of Schizophrenia Susceptibility Loci in the Urban Taiwanese Population.
Huang CC et al.·Medicina (Kaunas)
2024
Identification and functional analyses of disease-associated P4-ATPase phospholipid flippase variants in red blood cells.
Liou AY et al.·J Biol Chem
2019Functional
Cryptic 13q34 and 4q35.2 Deletions in an Italian Family.
Riccardi F et al.·Cytogenet Genome Res
2015Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools