ATP8B1

ATPase phospholipid transporting 8B1, the group of ATPase phospholipid transporting

Basic information

Region (hg38): 18:57646426-57803315

Previous symbols: [ "FIC1", "BRIC", "PFIC1" ]

Links

ENSG00000081923

∙ NCBI:5205 ∙ OMIM:602397 ∙ HGNC:3706 ∙ Uniprot:O43520 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

cholestasis, intrahepatic, of pregnancy, 1 (Limited), mode of inheritance: Unknown
progressive familial intrahepatic cholestasis type 1 (Definitive), mode of inheritance: AR
progressive familial intrahepatic cholestasis type 1 (Definitive), mode of inheritance: AR
progressive familial intrahepatic cholestasis type 1 (Supportive), mode of inheritance: AR
progressive familial intrahepatic cholestasis type 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Familial intrahepatic cholestasis, recurrent; Cholestasis, progressive familial intrahepatic 1; Intrahepatic cholestasis of pregnancy	AD/AR	Gastrointestinal; Obstetric	In severe forms, specific nutritional care may be beneficial (eg, including specific vitamin E supplementation); Hepatic manifestations may result in death in adolescence/early adulthood without surgical intervention; In pregnancy, Cholestasis, familial intrahepatic, of pregnancy, can cause severe sequelae (including death) in the fetus, as well as adverse maternal health outcomes, and precautions, including early delivery may be beneficial	Gastrointestinal; Obstetric	13840084; 5807632; 5762004; 5049818; 1218817; 3564958; 8088298; 7912266; 9500542; 9918928; 11093741; 15239083; 15448432; 15888793; 15657619; 20301474

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATP8B1 gene.

not_provided (710 variants)
Progressive_familial_intrahepatic_cholestasis_type_1 (136 variants)
ATP8B1-related_disorder (122 variants)
Inborn_genetic_diseases (104 variants)
Benign_recurrent_intrahepatic_cholestasis_type_1 (80 variants)
not_specified (71 variants)
Cholestasis,_intrahepatic,_of_pregnancy,_1 (36 variants)
Progressive_familial_intrahepatic_cholestasis (19 variants)
Familial_intrahepatic_cholestasis_type_1 (2 variants)
Alagille_syndrome,_ATP8B1_related (1 variants)
Progressive_familial_intrahepatic_cholestasis_type_2 (1 variants)
Intrahepatic_cholestasis_with_episodic_jaundice (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP8B1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001374385.1. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar	1 clinvar	7 clinvar	324 clinvar	5 clinvar	338
missense	7 clinvar	23 clinvar	225 clinvar	21 clinvar	5 clinvar	281
nonsense	26 clinvar	12 clinvar				38
start loss						0
frameshift	27 clinvar	18 clinvar	1 clinvar			46
splice donor/acceptor (+/-2bp)	4 clinvar	16 clinvar				20
Total	65	70	233	345	10

Highest pathogenic variant AF is 0.000159279

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATP8B1	protein_coding	protein_coding	ENST00000536015	27	156676

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.77e-10	1.00	125664	0	84	125748	0.000334

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.49	515	701	0.735	0.0000412	8262
Missense in Polyphen		169	283.67	0.59576		3412
Synonymous	-0.230	273	268	1.02	0.0000174	2342
Loss of Function	4.59	29	70.6	0.411	0.00000391	789

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000853	0.000853
Ashkenazi Jewish	0.00	0.00
East Asian	0.000382	0.000381
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000390	0.000387
Middle Eastern	0.000382	0.000381
South Asian	0.000229	0.000229
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

Function: FUNCTION: Catalytic component of a P4-ATPase flippase complex 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 play a role in asymmetric distribution of phospholipids in the canicular membrane. May have a role in transport of bile acids into the canaliculus, uptake of bile acids from intestinal contents into intestinal mucosa or both. In cooperation with ABCB4 may be involved in establishing integrity of the canalicular membrane thus protecting hepatocytes from bile salts. Together with TMEM30A is involved in uptake of the synthetic drug alkylphospholipid perifosine. Involved in the microvillus formation in polarized epithelial cells; the function seems to be independent from its flippase activity. Required for the preservation of cochlear hair cells in the inner ear. May act as cardiolipin transporter during inflammatory injury. {ECO:0000269|PubMed:17948906, ECO:0000269|PubMed:20510206, ECO:0000269|PubMed:20512993}.;
Disease: DISEASE: Cholestasis, benign recurrent intrahepatic, 1 (BRIC1) [MIM:243300]: A disorder characterized by intermittent episodes of cholestasis without progression to liver failure. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months. The cholestatic attacks vary in severity and duration. Patients are asymptomatic between episodes, both clinically and biochemically. {ECO:0000269|PubMed:15239083, ECO:0000269|PubMed:19731236, ECO:0000269|PubMed:9500542, ECO:0000269|PubMed:9918928}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cholestasis of pregnancy, intrahepatic 1 (ICP1) [MIM:147480]: A liver disorder of pregnancy. It presents during the second or, more commonly, the third trimester of pregnancy with intense pruritus which becomes more severe with advancing gestation and cholestasis. Cholestasis results from abnormal biliary transport from the liver into the small intestine. ICP1 causes fetal distress, spontaneous premature delivery and intrauterine death. ICP1 patients have spontaneous and progressive disappearance of cholestasis after delivery. {ECO:0000269|PubMed:15657619, ECO:0000269|PubMed:15888793, ECO:0000269|PubMed:19731236}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;
Pathway: Ion channel transport;Purine metabolism;Transport of small molecules;Phosphatidylinositol phosphate metabolism;Glycerophospholipid metabolism;Vitamin A (retinol) metabolism;Ion transport by P-type ATPases (Consensus)

Recessive Scores

pRec: 0.167

Intolerance Scores

loftool: 0.317
rvis_EVS: 0.1
rvis_percentile_EVS: 60.76

Haploinsufficiency Scores

pHI: 0.144
hipred: Y
hipred_score: 0.597
ghis: 0.463

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap
gene_indispensability_pred: N
gene_indispensability_score: 0.405

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Atp8b1
Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype;

Gene ontology

Biological process: drug transmembrane transport;Golgi organization;sensory perception of sound;bile acid and bile salt transport;regulation of microvillus assembly;ion transmembrane transport;phospholipid translocation;negative regulation of transcription, DNA-templated
Cellular component: endoplasmic reticulum;Golgi apparatus;plasma membrane;integral component of plasma membrane;apical plasma membrane;stereocilium
Molecular function: magnesium ion binding;phospholipid-translocating ATPase activity;protein binding;ATP binding