ATP8B2

Chr 1

ATPase phospholipid transporting 8B2

Also known as: ATPID

NCBI Gene: 57198 ENSG00000143515 UniProt: P98198

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. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

Research

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.41

Clinical Summary— ATP8B2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.

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ClinVar Variants

125 VUS of 158 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.41LOEUF

pLI 0.006

Z-score 5.35

OE 0.27 (0.18–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.87Z-score

OE missense 0.70 (0.65–0.75)

512 obs / 730.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.27 (0.18–0.41)

0≤0.351.4

Missense OE?0.70 (0.65–0.75)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 17 / 62.7Missense obs/exp: 512 / 730.1Syn Z: 1.09

This gene — mechanism propensity

0.75top 25%

GOF

0.77top 25%

LOF

0.2386th %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

158 submitted variants in ClinVar

ClinVar

Classification Summary

VUS125

Likely Benign2

Benign2

125

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	87	38	0	125
Likely Benign	0	0	2	2
Benign	0	0	2	2
Total	87	38	4	129

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap ATP8B2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →