ATP8A2

Chr 13AR

ATPase phospholipid transporting 8A2

Also known as: ATP, ATPIB, CAMRQ4, IB, ML-1

ATP8A2 encodes a P4-ATPase flippase that translocates phospholipids (particularly phosphatidylserine) from the outer to inner membrane leaflet to maintain membrane asymmetry and support vesicle trafficking in neuronal cells. Mutations cause cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome 4 with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants and the protein is required for normal visual and auditory function as well as photoreceptor and inner ear spiral ganglion cell survival.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.601 OMIM phenotype
Clinical SummaryATP8A2
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Gene-Disease Validity (ClinGen)
cerebellar ataxia, intellectual disability, and dysequilibrium · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
56 unique Pathogenic / Likely Pathogenic· 182 VUS of 399 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.60LOEUF
pLI 0.000
Z-score 4.39
OE 0.45 (0.340.60)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.30Z-score
OE missense 0.75 (0.690.81)
490 obs / 655.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.45 (0.340.60)
00.351.4
Missense OE0.75 (0.690.81)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 33 / 73.7Missense obs/exp: 490 / 655.4Syn Z: 0.61
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedATP8A2-related cerebellar ataxia, intellectual developmental disorder, and dysequilibrium syndromeOTHERAR

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

DN
0.78top 25%
GOF
0.78top 25%
LOF
0.2386th %ile

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.

ClinVar Variant Classifications

399 submitted variants in ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic26
VUS182
Likely Benign113
Benign30
Conflicting12
30
Pathogenic
26
Likely Pathogenic
182
VUS
113
Likely Benign
30
Benign
12
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
0
18
0
30
Likely Pathogenic
20
3
3
0
26
VUS
0
159
22
1
182
Likely Benign
0
5
42
66
113
Benign
0
1
21
8
30
Conflicting
12
Total3216810675393

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

View in ClinVar →

Protein Context — Lollipop Plot

ATP8A2 · 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.

Search ClinicalTrials.gov →
Clinical Literature
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