ATP8B3

protein-coding

ATPase phospholipid transporting 8B3, the group of ATPase phospholipid transporting

Gene summary

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 the other. This gene encodes member 3 of phospholipid-transporting ATPase 8B; other members of this protein family are located on chromosomes 1, 15 and 18. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

MANE transcript

NM_138813.4

Inheritance

—

ClinVar variants

P:1U:264B:35

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.79

Max pathogenic AF

—

Genomic locus

chr19:1,782,075-1,812,276

External References & Databases

Ensembl (ENSG00000130270)

Transcript & Mutation Effects

hg38 • Region Span ~30.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ATP8B3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 273

not providedTotal: 27

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138813.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	8 clinvar	4 clinvar	13
missense			261 clinvar	18 clinvar		279
nonsense		1 clinvar	1 clinvar		1 clinvar	3
start loss						0
frameshift				2 clinvar		2
splice donor/acceptor (+/-2bp)			1 clinvar	2 clinvar		3
Total	0	1	264	30	5	300

Highest pathogenic variant AF is 0.000009941964

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138813.4	RefSeq	NP_620168.1	28	MANE Select
ENST00000310127.10	Ensembl	ENSP00000311336.6	28	MANE Select
NM_001178002.3	RefSeq	NP_001171473.1	28	Standard
ENST00000525591.5	Ensembl	ENSP00000437115.1	28	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ion channel transport
Transport of small molecules
Phosphatidylinositol phosphate metabolism
Glycerophospholipid metabolism
Vitamin A (retinol) metabolism

Biological Process

Golgi organization
binding of sperm to zona pellucida
phospholipid translocation

Molecular Function

magnesium ion binding
phospholipid-translocating ATPase activity
ATP binding

Cellular Component

acrosomal membrane
endoplasmic reticulum membrane
Golgi apparatus
plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000310127
Coding exons: 28
Length: 30202
Individuals with no LoFs: 124091
Homozygous LoFs: 4
Heterozygous LoFs: 824
Defined: 124919
p: 0.00332

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.300	813	789	1.03	0.0000474	8417
Missense (PolyPhen)		267	282.18	0.94622		2945
Synonymous	-1.38	366	334	1.10	0.0000216	2529
Loss of Function	1.48	47	59.3	0.793	0.00000271	681

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0030	0.0029	notable
Latino/Admixed American	0.00085	0.00084	rare
Ashkenazi Jewish	0.016	0.016	notable
East Asian	0.011	0.010	notable
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.0027	0.0027	notable
South Asian	0.0032	0.0031	notable
Other	0.0024	0.0023	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: P4-ATPase flippase which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. May be responsible for the maintenance of asymmetric distribution of phosphatidylserine (PS) in spermatozoa membranes. Involved in acrosome reactions and binding of spermatozoa to zona pellucida. {ECO:0000250|UniProtKB:Q6UQ17}.;

Intolerance Scores

LoFtool: 0.391
RVIS EVS: -0.45
RVIS percentile EVS: 24.22

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.149

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	High	Medium	High
Cancer	High	High	High