ATP10A

Chr 15

ATPase phospholipid transporting 10A (putative)

Also known as: ATP10C, ATPVA, ATPVC

NCBI Gene: 57194 ENSG00000206190 UniProt: O60312 OMIM: 605855

This gene encodes a P4-ATPase flippase that transports phosphatidylcholine from the outer to inner leaflet of the plasma membrane, facilitating membrane bending and integrin endocytosis. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically presenting in early childhood. The gene is highly constrained against loss-of-function variants and is maternally expressed, located within the common deletion interval associated with Angelman syndrome.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of aminophospholipid-transporting ATPases. The aminophospholipid translocases transport phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to another. This gene is maternally expressed. It maps within the most common interval of deletion responsible for Angelman syndrome, also known as 'happy puppet syndrome'. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.43

Clinical Summary— ATP10A

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 243 VUS of 368 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ATP10A

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.43LOEUF

pLI 0.002

Z-score 5.12

OE 0.28 (0.19–0.43)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.76Z-score

OE missense 0.93 (0.88–0.98)

824 obs / 887.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.28 (0.19–0.43)

0≤0.351.4

Missense OE?0.93 (0.88–0.98)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 17 / 59.7Missense obs/exp: 824 / 887.7Syn Z: 0.00

This gene — mechanism propensity

0.77top 25%

GOF

0.77top 25%

LOF

0.2581th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). 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

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.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

368 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS243

Likely Benign63

Benign33

Conflicting2

Pathogenic

243

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	1	0	1
Likely Pathogenic	0	0	0	0	0
VUS	1	242	0	0	243
Likely Benign	0	26	6	31	63
Benign	0	16	3	14	33
Conflicting	—				2
Total	1	284	10	45	342

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

View in ClinVar →

314 pathogenic / likely-pathogenic (of 321) ClinVar copy-number / structural variants overlap ATP10A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →