ATP9A

Chr 20

ATPase phospholipid transporting 9A

Also known as: ATPIIA, NEDGBA

NCBI Gene: 10079 ENSG00000054793 UniProt: O75110

ATP9A regulates membrane trafficking between endosomes, the plasma membrane, and trans-Golgi network, and is required for maintaining neurite morphology and synaptic transmission. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with poor growth and behavioral abnormalities. This gene is highly intolerant to loss-of-function variants in the general population.

ResearchSummary from RefSeq, OMIM, UniProt

Enables protease binding activity. Involved in negative regulation of exosomal secretion; regulation of endocytic recycling; and regulation of retrograde transport, endosome to Golgi. Located in several cellular components, including endosome; perinuclear region of cytoplasm; and trans-Golgi network membrane. Implicated in neurodevelopmental disorder with poor growth and behavioral abnormalities. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with poor growth and behavioral abnormalities

Clinical highlights

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.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.20

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.20LOEUF

pLI 1.000

Z-score 6.62

OE 0.11 (0.06–0.20)

Highly constrained

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

Missense Constraint?

4.15Z-score

OE missense 0.54 (0.49–0.59)

347 obs / 643.6 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.11 (0.06–0.20)

0≤0.351.4

Missense OE?0.54 (0.49–0.59)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 7 / 64.2Missense obs/exp: 347 / 643.6Syn Z: -1.88

Background carrier burden — how many people carry a rare variant somewhere in ATP9A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 93

1,009 rare PASS variants

Rare truncating (LoF)

1 in 2,000

108 rare PASS variants

Rare synonymous (reference)

1 in 54

613 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ATP9A. 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 100	1 in 2,000
South Asian	~43k	1 in 69	1 in 4,700
Remaining (unassigned)	~30k	1 in 94	1 in 770
European (Finnish)	~27k	1 in 150	1 in 2,900
Admixed American	~22k	1 in 100	1 in 3,700
African / African American	~21k	1 in 100	1 in 3,000
East Asian	~20k	1 in 67	1 in 3,000
Ashkenazi Jewish	~13k	1 in 190	1 in 1,600
Middle Eastern	~2,884	1 in 100	≈ 1 in 2,900

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 28 coding exons well covered in gnomAD exomes; exons 1, 3 marginal. Genomes: 26 of 28 (exons 1, 10 below).? see exons ↓