ATP8B1 ATPase phospholipid transporting 8B1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ATP8B1provided by HGNC
Official Full Name: ATPase phospholipid transporting 8B1provided by HGNC
Primary source: HGNC:HGNC:3706
See related: Ensembl:ENSG00000081923 MIM:602397
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: BRIC; FIC1; ICP1; PFIC; ATPIC; PFIC1
Summary: This gene encodes a member of the P-type cation transport ATPase family, which belongs to the subfamily of aminophospholipid-transporting ATPases. The aminophospholipid translocases transport phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to another. Mutations in this gene may result in progressive familial intrahepatic cholestasis type 1 and in benign recurrent intrahepatic cholestasis. [provided by RefSeq, Jul 2008]
Expression: Broad expression in colon (RPKM 52.5), stomach (RPKM 26.5) and 17 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 18q21.31

Exon count:: 28

Annotation release	Status	Assembly	Chr	Location
109.20190607	current	GRCh38.p13 (GCF_000001405.39)	18	NC_000018.10 (57646426..57803822, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	18	NC_000018.9 (55313658..55470327, complement)

Chromosome 18 - NC_000018.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Mutations in the genes responsible for PFIC may be involved in both young and adults with cryptogenic cholestasis in a considerable number of cases, including in heterozygous status.
Title: Cryptogenic cholestasis in young and adults: ATP8B1, ABCB11, ABCB4, and TJP2 gene variants analysis by high-throughput sequencing.
FIC1, BSEP, and MDR3 represent hepatobiliary transport proteins essential for bile formation.
Title: Sequencing of FIC1, BSEP and MDR3 in a large cohort of patients with cholestasis revealed a high number of different genetic variants.
ATP8B1 deficiency caused incomplete polarization of human peripheral blood monocyte-derived macrophages into M2c, a subset alternatively activated macrophages.
Title: Assessment of ATP8B1 Deficiency in Pediatric Patients With Cholestasis Using Peripheral Blood Monocyte-Derived Macrophages.
the first characterisation at the protein level of six ABCB4 variants (D243A, K435T, G535D, I490T, R545C, and S978P) previously found in patients with inflammatory liver diseases or liver cancer, is reported.
Title: ABCB4 missense mutations D243A, K435T, G535D, I490T, R545C, and S978P significantly impair the lipid floppase and likely predispose to secondary pathologies in the human population.
Patients with a confirmed ABCB11 or tight junction protein 2 gene mutation (n = 7) had a minimally detectable THBA proportion (0.23-2.99% of total BAs). Three patients with an ATP8B1 mutation had an elevated THBA proportion (7.51-37.26%).
Title: Prognostic roles of tetrahydroxy bile acids in infantile intrahepatic cholestasis.
The lipid flippases, ATP8B1 and ATP11A are novel elements of the innate immune response that are essential to attenuate the inflammatory response, possibly by mediating endotoxin-induced internalization of TLR4.
Title: Phospholipid flippases attenuate LPS-induced TLR4 signaling by mediating endocytic retrieval of Toll-like receptor 4.
ATP8B1 is important for proper CFTR expression and function.
Title: The phospholipid flippase ATP8B1 mediates apical localization of the cystic fibrosis transmembrane regulator.
GGT levels in patients with ATP8B1 or ABCB11 deficiency varied with age. The peak GGT value was <70U/L in the 2nd~6th month of life, <60U/L in the 7th~12th month and <50U/L beyond one year
Title: The Features of GGT in Patients with ATP8B1 or ABCB11 Deficiency Improve the Diagnostic Efficiency.
As hypothyroidism can be another extrahepatic feature of ATP8B1 deficiency, thyroid function should be monitored in these patients.
Title: Hypothyroidism Associated with ATP8B1 Deficiency.
the predominant P4 ATPases in pure pancreatic beta cells and human and rat pancreatic islets were ATP8B1, ATP8B2, and ATP9A. ATP8B1 and CDC50A were highly concentrated in ISG
Title: Characterization of P4 ATPase Phospholipid Translocases (Flippases) in Human and Rat Pancreatic Beta Cells: THEIR GENE SILENCING INHIBITS INSULIN SECRETION.

Submit: New GeneRIF Correction See all GeneRIFs (43)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Cholestasis of pregnancy MedGen: C3549845 OMIM: 147480 GeneReviews: Not available	Compare labs
Cholestasis, benign recurrent intrahepatic 1 MedGen: C1855731 OMIM: 243300 GeneReviews: ATP8B1 Deficiency	Compare labs
Progressive intrahepatic cholestasis MedGen: C4551898 OMIM: 211600 GeneReviews: ATP8B1 Deficiency	Compare labs

NHGRI GWAS Catalog

Description
Conduct disorder and ADHD: evaluation of conduct problems as a categorical and quantitative trait in the international multicentre ADHD genetics study. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genetic Loci Associated with Circulating Levels of Very Long-Chain Saturated Fatty Acids. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study of generalized vitiligo in an isolated European founder population identifies SMOC2, in close proximity to IDDM8. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Ion channel transport, organism-specific biosystem (from REACTOME)
Ion channel transport, organism-specific biosystemIon channels mediate the flow of ions across the plasma membrane of cells. They are integral membrane proteins, typically a multimer of proteins, which, when arranged in the membrane, create a pore f...
Ion transport by P-type ATPases, organism-specific biosystem (from REACTOME)
Ion transport by P-type ATPases, organism-specific biosystemThe P-type ATPases (E1-E2 ATPases) are a large group of evolutionarily related ion pumps that are found in bacteria, archaea and eukaryotes. They are referred to as P-type ATPases because they catal...
Transmembrane transport of small molecules, organism-specific biosystem (from REACTOME)
Transmembrane transport of small molecules, organism-specific biosystem
Transmembrane transport of small molecules

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

L17705 (e-PCR)
- UniSTS:66091

G36359 (e-PCR)
- UniSTS:79161

D18S381 (e-PCR)
- UniSTS:44910

L17877 (e-PCR)
- UniSTS:61334

G65640 (e-PCR)
- UniSTS:225431

L17971 (e-PCR)
- UniSTS:43966

RH80031 (e-PCR)
- UniSTS:91103

Homology

Homologs of the ATP8B1 gene: The ATP8B1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 265 organisms have orthologs with human gene ATP8B1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
aminophospholipid transmembrane transporter activity	IEA Inferred from Electronic Annotation more info
cardiolipin binding	IEA Inferred from Electronic Annotation more info
magnesium ion binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
Golgi organization	IBA Inferred from Biological aspect of Ancestor more info	PubMed
bile acid and bile salt transport	NAS Non-traceable Author Statement more info	PubMed
bile acid metabolic process	IEA Inferred from Electronic Annotation more info
drug transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
inner ear receptor cell development	IEA Inferred from Electronic Annotation more info
ion transmembrane transport	TAS Traceable Author Statement more info
negative regulation of transcription, DNA-templated	IMP Inferred from Mutant Phenotype more info	PubMed
phospholipid translocation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
phospholipid translocation	IDA Inferred from Direct Assay more info	PubMed
phospholipid translocation	NAS Non-traceable Author Statement more info	PubMed
regulation of microvillus assembly	IMP Inferred from Mutant Phenotype more info	PubMed
sensory perception of sound	IEA Inferred from Electronic Annotation more info
vestibulocochlear nerve formation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
Golgi apparatus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
brush border membrane	IEA Inferred from Electronic Annotation more info
endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
integral component of plasma membrane	NAS Non-traceable Author Statement more info	PubMed
plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info
stereocilium	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: phospholipid-transporting ATPase IC

Names: ATPase, aminophospholipid transporter, class I, type 8B, member 1; ATPase, class I, type 8B, member 1; E1-E2 ATPase; P4-ATPase flippase complex alpha subunit ATP8B1; familial intrahepatic cholestasis type 1; probable phospholipid-transporting ATPase IC

NP_005594.2

EC 7.6.2.1

XP_006722544.1

EC 7.6.2.1

XP_011524325.1

EC 7.6.2.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007148.3 RefSeqGene

Range

5508..162397

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1205

mRNA and Protein(s)

NM_005603.6 → NP_005594.2 phospholipid-transporting ATPase IC

Status: REVIEWED

Source sequence(s)

AC022724, AC027097

Consensus CDS

CCDS11965.1

Related

ENSP00000497896.1, ENST00000648908.1

Conserved Domains (1) summary

cd02073
Location:94 → 1051

P-type_ATPase_APLT_Dnf-like; Aminophospholipid translocases (APLTs), similar to Saccharomyces cerevisiae Dnf1-3p, Drs2p, and human ATP8A2, -10D, -11B, -11C

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000018.10 Reference GRCh38.p13 Primary Assembly

Range

57646426..57803822 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011526023.3 → XP_011524325.1 phospholipid-transporting ATPase IC isoform X2

Conserved Domains (5) summary

TIGR01652
Location:75 → 1141

ATPase-Plipid; phospholipid-translocating P-type ATPase, flippase

pfam00122
Location:133 → 196

E1-E2_ATPase; E1-E2 ATPase

pfam13246
Location:495 → 590

Cation_ATPase; Cation transport ATPase (P-type)

pfam16212
Location:881 → 1135

PhoLip_ATPase_C; Phospholipid-translocating P-type ATPase C-terminal

cl21460
Location:837 → 881

HAD_like; Haloacid Dehalogenase-like Hydrolases
XM_006722481.4 → XP_006722544.1 phospholipid-transporting ATPase IC isoform X1

See identical proteins and their annotated locations for XP_006722544.1

UniProtKB/Swiss-Prot

O43520

Conserved Domains (1) summary

cd02073
Location:94 → 1051

P-type_ATPase_APLT_Dnf-like; Aminophospholipid translocases (APLTs), similar to Saccharomyces cerevisiae Dnf1-3p, Drs2p, and human ATP8A2, -10D, -11B, -11C