ATP8B1
Basic information
Region (hg38): 18:57646426-57803315
Previous symbols: [ "FIC1", "BRIC", "PFIC1" ]
Links
Phenotypes
GenCC
Source:
- 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:
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
- not provided (45 variants)
- Benign recurrent intrahepatic cholestasis type 1 (18 variants)
- Progressive familial intrahepatic cholestasis type 1 (18 variants)
- ATP8B1-related disorder (4 variants)
- Familial intrahepatic cholestasis type 1 (2 variants)
- Progressive familial intrahepatic cholestasis (2 variants)
- not specified (1 variants)
- Inborn genetic diseases (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.
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.
Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
---|---|---|---|---|---|---|
synonymous | 272 | 282 | ||||
missense | 13 | 144 | 10 | 177 | ||
nonsense | 26 | 11 | 37 | |||
start loss | 0 | |||||
frameshift | 22 | 15 | 38 | |||
inframe indel | 3 | |||||
splice donor/acceptor (+/-2bp) | 11 | 17 | ||||
splice region | 1 | 2 | 7 | 48 | 3 | 61 |
non coding | 45 | 151 | 119 | 316 | ||
Total | 58 | 51 | 199 | 433 | 129 |
Highest pathogenic variant AF is 0.0000526
Variants in ATP8B1
This is a list of pathogenic ClinVar variants found in the ATP8B1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
18-57646472-AT-A | Progressive familial intrahepatic cholestasis | Benign (Jun 14, 2016) | ||
18-57646543-G-A | Progressive familial intrahepatic cholestasis type 1 | Uncertain significance (Jan 13, 2018) | ||
18-57646548-T-C | Progressive familial intrahepatic cholestasis type 1 | Benign (Jan 13, 2018) | ||
18-57646551-A-T | Progressive familial intrahepatic cholestasis type 1 | Benign (Jan 12, 2018) | ||
18-57646637-C-G | Progressive familial intrahepatic cholestasis type 1 | Uncertain significance (Apr 27, 2017) | ||
18-57646655-C-T | Progressive familial intrahepatic cholestasis type 1 | Uncertain significance (Jan 13, 2018) | ||
18-57646692-C-T | Progressive familial intrahepatic cholestasis type 1 | Uncertain significance (Jan 17, 2018) | ||
18-57646765-C-T | Progressive familial intrahepatic cholestasis type 1 | Benign (Jan 13, 2018) | ||
18-57646812-C-T | Progressive familial intrahepatic cholestasis type 1 | Uncertain significance (Jan 13, 2018) | ||
18-57646859-A-G | Progressive familial intrahepatic cholestasis type 1 | Uncertain significance (Mar 30, 2018) | ||
18-57646935-A-C | Progressive familial intrahepatic cholestasis type 1 | Likely benign (Jan 12, 2018) | ||
18-57646942-T-G | Progressive familial intrahepatic cholestasis type 1 | Uncertain significance (Jan 13, 2018) | ||
18-57646964-A-G | Progressive familial intrahepatic cholestasis type 1 | Uncertain significance (Jan 12, 2018) | ||
18-57646979-T-C | Progressive familial intrahepatic cholestasis type 1 | Benign (Jan 13, 2018) | ||
18-57647085-C-T | Progressive familial intrahepatic cholestasis type 1 | Uncertain significance (Jan 12, 2018) | ||
18-57647155-A-C | Progressive familial intrahepatic cholestasis type 1 | Uncertain significance (Jan 13, 2018) | ||
18-57647234-A-G | Progressive familial intrahepatic cholestasis type 1 | Benign (Jan 13, 2018) | ||
18-57647245-A-G | Progressive familial intrahepatic cholestasis type 1 | Uncertain significance (Jan 12, 2018) | ||
18-57647355-T-C | Progressive familial intrahepatic cholestasis type 1 | Uncertain significance (Jan 12, 2018) | ||
18-57647393-T-A | Progressive familial intrahepatic cholestasis type 1 | Uncertain significance (Jan 13, 2018) | ||
18-57647405-A-G | Progressive familial intrahepatic cholestasis type 1 | Uncertain significance (Jan 13, 2018) | ||
18-57647520-A-T | Progressive familial intrahepatic cholestasis type 1 | Uncertain significance (Jan 12, 2018) | ||
18-57647588-C-A | Progressive familial intrahepatic cholestasis type 1 | Benign (Jan 13, 2018) | ||
18-57647588-C-T | Progressive familial intrahepatic cholestasis type 1 | Likely benign (Jan 13, 2018) | ||
18-57647589-G-A | Progressive familial intrahepatic cholestasis type 1 | Uncertain significance (Apr 27, 2017) |
GnomAD
Source:
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:
- 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