ATP9A

Chr 20AR

ATPase phospholipid transporting 9A

Also known as: ATPIIA, NEDGBA

NCBI Gene: 10079 ENSG00000054793 UniProt: O75110 OMIM: 609126

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.201 OMIM phenotype

Clinical Summary— ATP9A

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

14 unique Pathogenic / Likely Pathogenic· 110 VUS of 175 total submissions

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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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateATP9A-related neurodevelopmental disorderOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.5082th %ile

GOF

0.6736th %ile

LOF

0.51top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

175 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9

Likely Pathogenic5

VUS110

Likely Benign16

Benign5

Pathogenic

Likely Pathogenic

110

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	8	0	1	0	9
Likely Pathogenic	5	0	0	0	5
VUS	0	107	3	0	110
Likely Benign	0	0	0	16	16
Benign	0	1	0	4	5
Total	13	108	4	20	145

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap ATP9A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →