ATP8B1

Summary

ATP8B1 (ATPase phospholipid transporting 8B1, HGNC:3706) is a protein-coding gene on chromosome 18q21.31, encoding Phospholipid-transporting ATPase IC (O43520). Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of phospholipids, in particular phosphatidylcholines (PC), from the outer to the inner leaflet of the plasma membrane.

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.

Source: NCBI Gene 5205 — RefSeq curated summary.

At a glance

• Gene–disease (curated): progressive familial intrahepatic cholestasis type 1 (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 16
• Clinical variants (ClinVar): 1,269 total — 88 pathogenic, 54 likely-pathogenic
• Phenotypes (HPO): 57
• MANE Select transcript: NM_001374385

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3706
Approved symbol	ATP8B1
Name	ATPase phospholipid transporting 8B1
Location	18q21.31
Locus type	gene with protein product
Status	Approved
Aliases	ATPIC, PFIC
Ensembl gene	ENSG00000081923
Ensembl biotype	protein_coding
OMIM	602397
Entrez	5205

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 18 protein_coding, 4 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000585322, ENST00000588255, ENST00000589147, ENST00000591728, ENST00000642462, ENST00000648039, ENST00000648467, ENST00000648908, ENST00000857621, ENST00000857622, ENST00000857623, ENST00000857624, ENST00000857625, ENST00000857626, ENST00000857627, ENST00000857628, ENST00000857629, ENST00000938298, ENST00000967606, ENST00000967607, ENST00000967608, ENST00000967609, ENST00000967610, ENST00000967611

RefSeq mRNA: 3 — MANE Select: NM_001374385 NM_001374385, NM_001374386, NM_005603

CCDS: CCDS11965

Canonical transcript exons

ENST00000648908 — 28 exons

Exon	Start	End
ENSE00000950248	57697618	57697688
ENSE00000950249	57695450	57695532
ENSE00000950251	57694582	57694670
ENSE00000950252	57691807	57691997
ENSE00000950254	57685072	57685115
ENSE00001011581	57688299	57688507
ENSE00001011599	57695171	57695329
ENSE00001011607	57684036	57684192
ENSE00001011612	57674834	57675022
ENSE00001159846	57650367	57650497
ENSE00001159854	57652034	57652172
ENSE00001159867	57653992	57654075
ENSE00001159874	57655194	57655417
ENSE00001159879	57661174	57661462
ENSE00001178636	57662483	57662615
ENSE00001178646	57668429	57668540
ENSE00001178652	57669318	57669482
ENSE00001178654	57671468	57671580
ENSE00001221193	57652484	57652729
ENSE00001221233	57667092	57667167
ENSE00001221355	57646426	57648712
ENSE00003460606	57704555	57704668
ENSE00003497000	57706490	57706587
ENSE00003508157	57701215	57701313
ENSE00003527912	57697795	57697867
ENSE00003667197	57701039	57701100
ENSE00003820923	57731627	57731832
ENSE00003839065	57802998	57803315

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.8558 / max 179.4195, expressed in 1223 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172120	4.5847	1017
172117	2.2776	702
172118	0.6507	275
172119	0.2818	153
172116	0.0610	25

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cardia of stomach	UBERON:0001162	99.58	gold quality
nipple	UBERON:0002030	99.56	gold quality
renal medulla	UBERON:0000362	99.50	gold quality
pylorus	UBERON:0001166	99.49	gold quality
ventral tegmental area	UBERON:0002691	99.38	gold quality
trigeminal ganglion	UBERON:0001675	99.27	gold quality
buccal mucosa cell	CL:0002336	99.24	gold quality
superior surface of tongue	UBERON:0007371	99.21	gold quality
superior vestibular nucleus	UBERON:0007227	99.13	gold quality
subthalamic nucleus	UBERON:0001906	99.12	gold quality
inferior vagus X ganglion	UBERON:0005363	99.00	gold quality
lateral globus pallidus	UBERON:0002476	98.92	gold quality
sperm	CL:0000019	98.90	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.89	gold quality
penis	UBERON:0000989	98.83	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.83	gold quality
pericardium	UBERON:0002407	98.81	gold quality
urethra	UBERON:0000057	98.76	gold quality
substantia nigra pars compacta	UBERON:0001965	98.76	gold quality
colonic mucosa	UBERON:0000317	98.71	gold quality
pharyngeal mucosa	UBERON:0000355	98.69	gold quality
medulla oblongata	UBERON:0001896	98.69	gold quality
vena cava	UBERON:0004087	98.67	gold quality
synovial joint	UBERON:0002217	98.61	gold quality
saphenous vein	UBERON:0007318	98.59	gold quality
jejunal mucosa	UBERON:0000399	98.38	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.31	gold quality
male germ cell	CL:0000015	98.21	gold quality
body of tongue	UBERON:0011876	98.14	gold quality
pons	UBERON:0000988	98.02	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	33.12
E-ANND-3	yes	14.06

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1H4

miRNA regulators (miRDB)

114 targeting ATP8B1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-651-3P	99.94	73.48	5177

Literature-anchored findings (GeneRIF, showing 40)

• three homologues found and two sequenced and two RNA transcript sizes analysed by northern blot: APT8B2, APT8B3, APT8B4 (PMID:12880872)
• Loss of familial intrahepatic cholestasis-1 leads to diminished nuclear translocation of farnesoid X receptor(FXR), with subsequent potential for pathologic alterations in intestinal and hepatic bile acid transporter expression (PMID:14988830)
• 54 distinct disease mutations: 10 mutations predicted to disrupt splicing, 6 nonsense mutations, 11 small insertion or deletion mutations predicted to induce frameshifts, 1 large genomic deletion, 2 small inframe deletions, and 24 missense mutations. (PMID:15239083)
• Loss of familial intrahepatic cholestasis-1 leads to diminished nuclear translocation of farnesoid X receptor(FXR), with subsequent potential for pathologic alterations in intestinal and hepatic bile acid transporter expression (PMID:15946126)
• Coexpression with CDC50 proteins resulted in relocalization of ATP8B1 from the endoplasmic reticulum to the plasma membrane. In the plasma membrane, ATP8B1 functions as a flippase for phosphatidylserine. (PMID:17948906)
• FIC1 signals to FXR via PKC zeta. FIC1-related liver disease is likely related to downstream effects of FXR on bile acid homeostasis. (PMID:18668687)
• ATP8B1 deficiency predisposes to cholestasis by favoring bile acid-induced injury in the canalicular membrane but does not directly affect FXR expression (PMID:19027009)
• Knockdown of ATP8B1 expression leads to specific downregulation of the bile acid sensor FXR in HepG2 cells: effect of the FXR agonist GW4064. (PMID:19228886)
• These results suggest that the PFIC1 mutants have a lower stimulatory effect on FXR activity and cannot interact with CDC50A, which may lead to the development of the features of PFIC1. (PMID:19381753)
• show that ATP8B1/Atp8b1 deficiency, both in patients and in Atp8b1(G308V/G308V) mutant mice, causes hearing loss, associated with progressive degeneration of cochlear hair cells (PMID:19478059)
• Post-liver transplantation steatosis may be due to a malfunction of the ATP8B1 product. (PMID:19479804)
• PFIC1 mutations lead to the complete absence of canalicular expression, whereas in BRIC1/ICP residual protein is expressed in the canalicular membrane. (PMID:19731236)
• Findings support the hypothesis that hepatocyte FIC1 enhances FXR signaling via a PKCzeta-dependent signaling pathway. (PMID:19809379)
• A surprisingly large proportion of ATP8B1 mutations resulted in aberrant folding and decreased expression at the plasma membrane. These effects were partially restored by treatment with 4-phenylbutyrate. (PMID:19918981)
• ATP8B1 gene mutations play an important role in Chinese patients with progressive intrahepatic cholestasis and low gamma-glutamyltransferase. The linked mutation P209T and IVS6+5G>T is a hot mutation in the Chinese population. (PMID:20038848)
• We now report evidence that heterozygous genetically determined alteration of ATP8B1 (encoding FIC1) may also represent a risk factor for transient neonatal cholestasis. (PMID:20216097)
• Progressive familial intrahepatic cholestasis types 1 & 2 differ clinically, biochemically, and histologically at presentation and/or during the disease course. A small proportion of normal-GGT PFIC is likely not due to ATP8B1 or ABCB11 mutations. (PMID:20232290)
• Data identified three novel mutations in BSEP, one novel mutation in MDR3, and one heterozygous mutation in ATP8B1 in PFIC patients. (PMID:20414253)
• facilitating diagnosis and elucidating the differing consequences of ATP8B1 and ABCB11 mutations in progressive familial intrahepatic cholestasis (PMID:20447715)
• critical role in apical membrane organization that is unrelated to its presumed aminophospholipid translocase activity (PMID:20512993)
• Sequence analysis of the genes identified 27% cholestasis subjects with missense, nonsense, deletion, and splice site variants associated with disease phenotypes based on the type of mutation in the JAG1, ATP8B1, ABCB11, or ABCB4 genes. (PMID:20683201)
• results unveil a new paradigm whereby Atp8b1 is a cardiolipin importer whose capacity to remove cardiolipin from lung fluid is exceeded during inflammation or when Atp8b1 is defective (PMID:20852622)
• Novel splice-site mutation in ATP8B1 results in atypical progressive familial intrahepatic cholestasis type 1. (PMID:23033845)
• Biochemical analysis of P4-ATPase mutations identified in patients with progressive familial intrahepatic cholestasis (PMID:23060447)
• Case Report: missense ATP8B1 mutation in adult male with progressive familial intrahepatic cholestasis type 1. (PMID:23197899)
• FIC1 signals to FXR via a signaling pathway including PLD2 and PKCzeta (PMID:23213138)
• The basal expression of ATP8B1 is driven by a housekeeping-like promoter located 71 kb upstream of the first protein coding exon, and is independent of bile acids and farnesoid X receptor. (PMID:23251605)
• Case Report: suggest contribution of ATP8B1 mutations to drug-induced liver injury from anabolic androgenic steroids marketed as dietary supplements. (PMID:23750872)
• We did not find an association between heterozygous ATP8B1 variants and chronic pancreatitis in our cohort of patients with hereditary and idiopathic chronic pancreatitis. (PMID:24260417)
• Data indicate that the lipid flippase (ATP8B1)-transmembrane protein 30A (CDC50A) heterodimer is essential for the apical localization of sodium-dependent bile acid transporter (SLC10A2/ASBT) in Caco-2 cells. (PMID:25239307)
• We systematically characterized the molecular consequences of 14 ATP8B1 mutations at exon-intron boundaries associated with ATP8B1 deficiency and found that the majority resulted in total exon skipping (PMID:25421123)
• insufficient activity of Atp8b1/FIC1 increases susceptibility to bacterial pneumonia. (PMID:26050466)
• 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 (PMID:26240149)
• As hypothyroidism can be another extrahepatic feature of ATP8B1 deficiency, thyroid function should be monitored in these patients. (PMID:26382629)
• GGT levels in patients with ATP8B1 or ABCB11 deficiency varied with age. The peak GGT value was <70U/L in the 2nd6th month of life, <60U/L in the 7th12th month and <50U/L beyond one year (PMID:27050426)
• ATP8B1 is important for proper CFTR expression and function. (PMID:27301931)
• 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. (PMID:27628304)
• 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%). (PMID:28073941)
• 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. (PMID:28220208)
• FIC1, BSEP, and MDR3 represent hepatobiliary transport proteins essential for bile formation. (PMID:28733223)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp8b1	ENSDARG00000060980
mus_musculus	Atp8b1	ENSMUSG00000039529
rattus_norvegicus	Atp8b1	ENSRNOG00000024952
drosophila_melanogaster	CG9981	FBGN0030746
drosophila_melanogaster	CG4301	FBGN0030747
drosophila_melanogaster	CG31729	FBGN0051729
caenorhabditis_elegans	tat-5	WBGENE00009498
caenorhabditis_elegans		WBGENE00017174

Paralogs (13): ATP9A (ENSG00000054793), ATP11B (ENSG00000058063), ATP11A (ENSG00000068650), ATP11C (ENSG00000101974), ATP8B4 (ENSG00000104043), ATP10B (ENSG00000118322), ATP8A1 (ENSG00000124406), ATP8B3 (ENSG00000130270), ATP8A2 (ENSG00000132932), ATP8B2 (ENSG00000143515), ATP10D (ENSG00000145246), ATP9B (ENSG00000166377), ATP10A (ENSG00000206190)

Protein

Protein identifiers

Phospholipid-transporting ATPase IC — O43520 (reviewed: O43520)

Alternative names: ATPase class I type 8B member 1, Familial intrahepatic cholestasis type 1, P4-ATPase flippase complex alpha subunit ATP8B1

All UniProt accessions (5): O43520, A0A2R8Y5C5, A0A3B3IRQ1, K7EQC4, K7ESK2

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of phospholipids, in particular phosphatidylcholines (PC), from the outer to the inner leaflet of the plasma membrane. May participate in the establishment of the canalicular membrane integrity by ensuring asymmetric distribution of phospholipids in the canicular membrane. Thus may have a role in the regulation of bile acids transport into the canaliculus, uptake of bile acids from intestinal contents into intestinal mucosa or both and protect hepatocytes from bile salts. Involved in the microvillus formation in polarized epithelial cells; the function seems to be independent from its flippase activity. Participates in correct apical membrane localization of CDC42, CFTR and SLC10A2. Enables CDC42 clustering at the apical membrane during enterocyte polarization through the interaction between CDC42 polybasic region and negatively charged membrane lipids provided by ATP8B1. Together with TMEM30A is involved in uptake of the synthetic drug alkylphospholipid perifosine. Required for the preservation of cochlear hair cells in the inner ear. May act as cardiolipin transporter during inflammatory injury.

Subunit / interactions. Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit ATP8B1 and an accessory beta subunit TMEM30A. The flippase ATP8B1:TMEM30A complex can form an intermediate phosphoenzyme in vitro. Also interacts with beta subunit TMEM30B.

Subcellular location. Cell membrane. Apical cell membrane. Cell projection. Stereocilium. Endoplasmic reticulum. Golgi apparatus.

Tissue specificity. Found in most tissues except brain and skeletal muscle. Most abundant in pancreas and small intestine.

Disease relevance. Cholestasis, progressive familial intrahepatic, 1 (PFIC1) [MIM:211600] A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC1 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.

RefSeq proteins (3): NP_001361314, NP_001361315, NP_005594 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001757	P_typ_ATPase	Family
IPR006539	P-type_ATPase_IV	Family
IPR008250	ATPase_P-typ_transduc_dom_A_sf	Homologous_superfamily
IPR018303	ATPase_P-typ_P_site	PTM
IPR023214	HAD_sf	Homologous_superfamily
IPR023298	ATPase_P-typ_TM_dom_sf	Homologous_superfamily
IPR023299	ATPase_P-typ_cyto_dom_N	Homologous_superfamily
IPR032630	P_typ_ATPase_c	Domain
IPR032631	P-type_ATPase_N	Domain
IPR036412	HAD-like_sf	Homologous_superfamily
IPR044492	P_typ_ATPase_HD_dom	Domain
IPR059000	ATPase_P-type_domA	Domain

Pfam: PF00122, PF13246, PF16209, PF16212

Enzyme classification (BRENDA):

• EC 7.6.2.1 — P-type phospholipid transporter (BRENDA: 22 organisms, 260 substrates, 62 inhibitors, 53 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.016–2.215	41
P-NITROPHENYL PHOSPHATE	1.17–1.46	3
ACETYL PHOSPHATE	1.03–1.31	2
1-PALMITOYL-2-OLEOYL-SN-GLYCERO-3-PHOSPHO-L-SERI	0.111	1

Catalyzed reactions (Rhea), 2 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-L-serine(out) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) + ADP + phosphate + H(+) (RHEA:38567)
• a 1,2-diacyl-sn-glycero-3-phosphocholine(out) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ADP + phosphate + H(+) (RHEA:38583)

UniProt features (211 total): helix 54, strand 48, sequence variant 45, binding site 18, turn 16, topological domain 11, transmembrane region 10, compositionally biased region 2, mutagenesis site 2, chain 1, region of interest 1, active site 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
8OX6	ELECTRON MICROSCOPY	2.39
8OX7	ELECTRON MICROSCOPY	2.56
8OXC	ELECTRON MICROSCOPY	2.58
8OX9	ELECTRON MICROSCOPY	2.72
8OXA	ELECTRON MICROSCOPY	2.76
8OX5	ELECTRON MICROSCOPY	2.9
8OX8	ELECTRON MICROSCOPY	2.98
8OXB	ELECTRON MICROSCOPY	2.99
7PY4	ELECTRON MICROSCOPY	3.1
7VGI	ELECTRON MICROSCOPY	3.36
7VGH	ELECTRON MICROSCOPY	3.39
8OX4	ELECTRON MICROSCOPY	3.4
7VGJ	ELECTRON MICROSCOPY	3.98

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43520-F1	80.42	0.36

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 454 (4-aspartylphosphate intermediate)

Ligand- & substrate-binding residues (18): 454; 454; 455; 456; 456; 555; 596; 619; 652; 732; 733; 734 …

Post-translational modifications (1): 1223

Mutagenesis-validated functional residues (2):

Position	Phenotype
234	impaired pc flippase activity.
454	greatly reduced expression due to proteosomal degradation; abolishes interaction with tmem30a.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-936837	Ion transport by P-type ATPases
R-HSA-382551	Transport of small molecules
R-HSA-983712	Ion channel transport

MSigDB gene sets: 353 (showing top): GOBP_APICAL_PROTEIN_LOCALIZATION, MORF_FLT1, MORF_MSH3, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, MORF_BRCA1, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_NEUROGENESIS, GOBP_CRANIAL_NERVE_MORPHOGENESIS, GOBP_XENOBIOTIC_TRANSMEMBRANE_TRANSPORT, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, GOBP_CRANIAL_NERVE_DEVELOPMENT

GO Biological Process (20): xenobiotic transmembrane transport (GO:0006855), Golgi organization (GO:0007030), sensory perception of sound (GO:0007605), bile acid metabolic process (GO:0008206), bile acid and bile salt transport (GO:0015721), vestibulocochlear nerve formation (GO:0021650), regulation of microvillus assembly (GO:0032534), monoatomic ion transmembrane transport (GO:0034220), apical protein localization (GO:0045176), phospholipid translocation (GO:0045332), negative regulation of DNA-templated transcription (GO:0045892), inner ear receptor cell development (GO:0060119), regulation of plasma membrane organization (GO:1903729), regulation of chloride transport (GO:2001225), lipid transport (GO:0006869), obsolete organic anion transport (GO:0015711), phospholipid transport (GO:0015914), aminophospholipid transport (GO:0015917), lipid translocation (GO:0034204), aminophospholipid translocation (GO:0140331)

GO Molecular Function (17): magnesium ion binding (GO:0000287), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), phosphatidylcholine floppase activity (GO:0090554), phosphatidylserine floppase activity (GO:0090556), ATPase-coupled intramembrane lipid carrier activity (GO:0140326), phosphatidylcholine flippase activity (GO:0140345), phosphatidylserine flippase activity (GO:0140346), cardiolipin binding (GO:1901612), nucleotide binding (GO:0000166), transporter activity (GO:0005215), lipid carrier activity (GO:0005319), protein binding (GO:0005515), obsolete phospholipid transporter activity (GO:0005548), aminophospholipid flippase activity (GO:0015247), metal ion binding (GO:0046872), flippase activity (GO:0140327)

GO Cellular Component (13): nucleoplasm (GO:0005654), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), cytosol (GO:0005829), plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), nuclear body (GO:0016604), stereocilium (GO:0032420), phospholipid-translocating ATPase complex (GO:1990531), endomembrane system (GO:0012505), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Ion channel transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
lipid transport	3
cytoplasm	3
transmembrane transport	2
phospholipid transport	2
ATP-dependent activity	2
phosphatidylcholine intramembrane carrier activity	2
floppase activity	2
glycerophospholipid flippase activity	2
endomembrane system	2
intracellular membrane-bounded organelle	2
xenobiotic transport	1
organelle organization	1
endomembrane system organization	1
sensory perception of mechanical stimulus	1
steroid metabolic process	1
monocarboxylic acid metabolic process	1
monocarboxylic acid transport	1
organic hydroxy compound transport	1
cranial nerve formation	1
vestibulocochlear nerve morphogenesis	1
microvillus assembly	1
regulation of microvillus organization	1
regulation of plasma membrane bounded cell projection assembly	1
monoatomic ion transport	1
intracellular protein localization	1
lipid translocation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
neuron development	1
inner ear receptor cell differentiation	1
plasma membrane organization	1
regulation of cellular component organization	1
chloride transport	1
regulation of monoatomic anion transport	1
transport	1
lipid localization	1
organophosphate ester transport	1
nitrogen compound transport	1

Protein interactions and networks

STRING

1270 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP8B1	ABCB11	O95342	990
ATP8B1	ABCB4	P21439	924
ATP8B1	CDC50A	Q9NV96	859
ATP8B1	NR1H4	Q96RI1	846
ATP8B1	NR0B2	Q15466	795
ATP8B1	CDC50B	Q3MIR4	768
ATP8B1	ABCC2	Q92887	744
ATP8B1	AKR1D1	P51857	648
ATP8B1	TJP2	Q9UDY2	638
ATP8B1	BAAT	Q14032	591
ATP8B1	SLC10A2	Q12908	589
ATP8B1	FABP6	P51161	585
ATP8B1	ABCG5	Q9H222	584
ATP8B1	SLC10A1	Q14973	576
ATP8B1	MYO5B	Q9ULV0	576

IntAct

17 interactions, top by confidence:

A	B	Type	Score
ATP8B1	TMEM30A	psi-mi:“MI:0915”(physical association)	0.880
ATP8B1	TMEM30A	psi-mi:“MI:0403”(colocalization)	0.880
TMEM30A	ATP8B1	psi-mi:“MI:0915”(physical association)	0.880
TMEM30B	ATP8B1	psi-mi:“MI:0915”(physical association)	0.740
ATP8B1	TMEM30B	psi-mi:“MI:0915”(physical association)	0.740
ATP8B1	TMEM30B	psi-mi:“MI:0403”(colocalization)	0.740
TMEM30B	ATP8B1	psi-mi:“MI:0403”(colocalization)	0.740
ATP8B1	NUP153	psi-mi:“MI:0407”(direct interaction)	0.440
	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): ATP8B1 (Affinity Capture-RNA), ATP8B1 (Affinity Capture-RNA), ATP8B1 (Synthetic Lethality), ATP8B1 (Affinity Capture-MS), ATP8B1 (Affinity Capture-RNA), CKAP4 (Cross-Linking-MS (XL-MS)), ATP8B1 (Affinity Capture-RNA), TMEM30A (Affinity Capture-Western), TMEM30B (Affinity Capture-Western)

ESM2 similar proteins: A1A4J6, D4ABB8, F1Q4S1, G5EBH1, O14072, O43520, O43861, O70228, O75110, P09626, P19156, P20648, P27112, P40527, P50996, P57792, P90747, P98195, P98196, P98197, P98198, P98199, Q10309, Q27533, Q3TYU2, Q4VNC1, Q4WYP6, Q5XF89, Q5XF90, Q5ZKB7, Q64436, Q6DFW5, Q8NB49, Q92126, Q93084, Q95JN5, Q9EPE9, Q9H7F0, Q9HD20, Q9LI83

Diamond homologs: A1A4J6, A3FIN4, B1AWN4, C7EXK4, D4AA47, D4ABB8, F1Q4S1, G0S196, G2X7W6, G5EBH1, O36028, O43520, O43861, O54827, O60312, O60423, O94296, O94823, P32660, P39524, P40527, P57792, P70704, P98195, P98196, P98197, P98198, P98199, P98200, P98204, P98205, Q09891, Q10309, Q12675, Q148W0, Q29449, Q37145, Q5BL50, Q6DFW5, Q6UQ17

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ATP8B1	up-regulates	ATP2B2

Disease & clinical

Clinical variants and AI predictions

ClinVar

1269 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	88
Likely pathogenic	54
Uncertain significance	366
Likely benign	493
Benign	128

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1195884	NM_001374385.1(ATP8B1):c.-25-4014_181+2209del	Pathogenic
1195885	NC_000018.9:g.55335906_55346620dup	Pathogenic
126382	NM_001374385.1(ATP8B1):c.1993G>T (p.Glu665Ter)	Pathogenic
1301678	NM_001374385.1(ATP8B1):c.3040C>T (p.Arg1014Ter)	Pathogenic
1687217	NM_001374385.1(ATP8B1):c.213dup (p.Lys72fs)	Pathogenic
1698723	NM_001374385.1(ATP8B1):c.2821C>T (p.Arg941Ter)	Pathogenic
1698811	NM_001374385.1(ATP8B1):c.1573C>T (p.Arg525Ter)	Pathogenic
2425385	NC_000018.9:g.(?55328386)(55328714_?)del	Pathogenic
2627551	NM_001374385.1(ATP8B1):c.2500_2588del (p.Met834fs)	Pathogenic
2679853	NM_001374385.1(ATP8B1):c.1214_1215del (p.Tyr405fs)	Pathogenic
2679854	NM_001374385.1(ATP8B1):c.811A>T (p.Arg271Ter)	Pathogenic
2687798	NM_001374385.1(ATP8B1):c.555-1G>C	Pathogenic
2687832	NM_001374385.1(ATP8B1):c.2614dup (p.Gln872fs)	Pathogenic
2699206	NM_001374385.1(ATP8B1):c.3082_3091del (p.Phe1028fs)	Pathogenic
2706283	NM_001374385.1(ATP8B1):c.2680_2681insTTATATAGATGAACGTG (p.Gly894delinsValIleTer)	Pathogenic
2713995	NM_001374385.1(ATP8B1):c.1172del (p.Gly391fs)	Pathogenic
2725205	NM_001374385.1(ATP8B1):c.1105dup (p.Ser369fs)	Pathogenic
2728500	NM_001374385.1(ATP8B1):c.3473_3476dup (p.Val1160fs)	Pathogenic
2736742	NM_001374385.1(ATP8B1):c.3069_3070del (p.Asp1025fs)	Pathogenic
2736744	NM_001374385.1(ATP8B1):c.2788C>T (p.Arg930Ter)	Pathogenic
2736746	NM_001374385.1(ATP8B1):c.1607_1608del (p.Thr536fs)	Pathogenic
2744846	NM_001374385.1(ATP8B1):c.426C>A (p.Tyr142Ter)	Pathogenic
2749908	NM_001374385.1(ATP8B1):c.2946_2947insGCTTGTATGTTTTTATCTTTATCTTTGGTTATTTTTTCATGTTGACATTAAGAGTAGCG (p.Trp983delinsAlaCysMetPheLeuSerLeuSerLeuValIlePheSerCysTer)	Pathogenic
2767042	NM_001374385.1(ATP8B1):c.1381C>T (p.Gln461Ter)	Pathogenic
2770196	NM_001374385.1(ATP8B1):c.3247del (p.Thr1083fs)	Pathogenic
2780781	NM_001374385.1(ATP8B1):c.3438G>A (p.Trp1146Ter)	Pathogenic
2801695	NM_001374385.1(ATP8B1):c.2947_2948insTGCTTGTATGTTTTTATCTTTATCTTTGGTTATTTTTTCATGTTGACATTAAGAGTAGCGT (p.Trp983fs)	Pathogenic
2830014	NM_001374385.1(ATP8B1):c.2131C>T (p.Gln711Ter)	Pathogenic
2833127	NM_001374385.1(ATP8B1):c.3113T>A (p.Leu1038Ter)	Pathogenic
2836172	NM_001374385.1(ATP8B1):c.1402A>T (p.Lys468Ter)	Pathogenic

SpliceAI

4105 predictions. Top by Δscore:

Variant	Effect	Δscore
18:57648708:TGGAT:T	acceptor_gain	1.0000
18:57648709:GGAT:G	acceptor_gain	1.0000
18:57648710:GAT:G	acceptor_gain	1.0000
18:57648711:AT:A	acceptor_gain	1.0000
18:57648713:C:CC	acceptor_gain	1.0000
18:57652185:C:CT	acceptor_gain	1.0000
18:57653987:CCTA:C	donor_loss	1.0000
18:57653988:CTAC:C	donor_loss	1.0000
18:57653990:A:AG	donor_loss	1.0000
18:57653991:C:A	donor_loss	1.0000
18:57654071:GCAGT:G	acceptor_gain	1.0000
18:57654072:CAGT:C	acceptor_gain	1.0000
18:57654072:CAGTC:C	acceptor_gain	1.0000
18:57654073:AGT:A	acceptor_gain	1.0000
18:57654074:GT:G	acceptor_gain	1.0000
18:57654075:TC:T	acceptor_loss	1.0000
18:57654076:C:CC	acceptor_gain	1.0000
18:57654076:CT:C	acceptor_loss	1.0000
18:57654077:T:G	acceptor_loss	1.0000
18:57655189:ATTAC:A	donor_loss	1.0000
18:57655190:TTA:T	donor_loss	1.0000
18:57655191:TAC:T	donor_loss	1.0000
18:57655193:C:G	donor_loss	1.0000
18:57655286:T:TA	donor_gain	1.0000
18:57655413:GGCAG:G	acceptor_gain	1.0000
18:57655414:GCAG:G	acceptor_gain	1.0000
18:57655415:CAG:C	acceptor_gain	1.0000
18:57655415:CAGC:C	acceptor_gain	1.0000
18:57655416:AG:A	acceptor_gain	1.0000
18:57655417:GCTAT:G	acceptor_loss	1.0000

AlphaMissense

8306 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:57655414:G:T	A904D	1.000
18:57661190:G:C	D897E	1.000
18:57661190:G:T	D897E	1.000
18:57661191:T:A	D897V	1.000
18:57661191:T:C	D897G	1.000
18:57661191:T:G	D897A	1.000
18:57661192:C:A	D897Y	1.000
18:57661192:C:G	D897H	1.000
18:57661193:A:C	N896K	1.000
18:57661193:A:T	N896K	1.000
18:57661200:C:T	G894E	1.000
18:57661201:C:A	G894W	1.000
18:57661201:C:G	G894R	1.000
18:57661201:C:T	G894R	1.000
18:57661203:T:A	D893V	1.000
18:57661203:T:G	D893A	1.000
18:57661206:C:A	G892V	1.000
18:57661206:C:T	G892E	1.000
18:57661207:C:G	G892R	1.000
18:57661207:C:T	G892R	1.000
18:57661215:A:G	L889P	1.000
18:57661262:C:A	K873N	1.000
18:57661262:C:G	K873N	1.000
18:57661264:T:G	K873Q	1.000
18:57661281:C:G	R867P	1.000
18:57661283:G:C	C866W	1.000
18:57661288:A:G	C865R	1.000
18:57667149:C:T	G743E	1.000
18:57667161:G:T	A739D	1.000
18:57667162:C:G	A739P	1.000

dbSNP variants (sampled 300 via entrez): RS1000024405 (18:57656446 C>T), RS1000034562 (18:57771674 A>G), RS1000049581 (18:57739765 A>G), RS1000051511 (18:57736921 T>C), RS1000054306 (18:57779615 T>C), RS1000102840 (18:57734898 C>A), RS1000106726 (18:57681782 C>T), RS1000115500 (18:57783938 A>G), RS1000142994 (18:57737240 C>A,T), RS1000230329 (18:57746298 T>C), RS1000230700 (18:57760998 A>C), RS1000245772 (18:57712038 C>A,T), RS1000276375 (18:57730928 T>A), RS1000299352 (18:57706825 T>C,G), RS1000317405 (18:57659875 T>G)

Disease associations

OMIM: gene MIM:602397 | disease phenotypes: MIM:243300, MIM:211600, MIM:147480, MIM:601847

GenCC curated gene-disease

Disease	Classification	Inheritance
progressive familial intrahepatic cholestasis type 1	Definitive	Autosomal recessive
cholestasis, intrahepatic, of pregnancy, 1	Strong	Autosomal dominant
progressive familial intrahepatic cholestasis	Strong	Autosomal recessive

Mondo (6): benign recurrent intrahepatic cholestasis type 1 (MONDO:0009469), progressive familial intrahepatic cholestasis type 1 (MONDO:0008892), familial intrahepatic cholestasis (MONDO:0017290), cholestasis, intrahepatic, of pregnancy, 1 (MONDO:0007829), progressive familial intrahepatic cholestasis (MONDO:0015762), progressive familial intrahepatic cholestasis type 2 (MONDO:0011156)

Orphanet (7): Benign recurrent intrahepatic cholestasis (Orphanet:65682), Benign recurrent intrahepatic cholestasis type 1 (Orphanet:99960), Progressive familial intrahepatic cholestasis type 1 (Orphanet:79306), Familial intrahepatic cholestasis (Orphanet:284385), Intrahepatic cholestasis of pregnancy (Orphanet:69665), Progressive familial intrahepatic cholestasis (Orphanet:172), Progressive familial intrahepatic cholestasis type 2 (Orphanet:79304)

HPO phenotypes

57 total (30 of 57 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000365	Hearing impairment
HP:0000421	Epistaxis
HP:0000716	Depression
HP:0000821	Hypothyroidism
HP:0000938	Osteopenia
HP:0000952	Jaundice
HP:0000988	Skin rash
HP:0000989	Pruritus
HP:0001046	Intermittent jaundice
HP:0001081	Cholelithiasis
HP:0001082	Cholecystitis
HP:0001337	Tremor
HP:0001394	Cirrhosis
HP:0001406	Intrahepatic cholestasis
HP:0001408	Bile duct proliferation
HP:0001508	Failure to thrive
HP:0001518	Small for gestational age
HP:0001541	Ascites
HP:0001622	Premature birth
HP:0001732	Abnormality of the pancreas
HP:0001733	Pancreatitis
HP:0001744	Splenomegaly
HP:0002014	Diarrhea
HP:0002024	Malabsorption
HP:0002027	Abdominal pain
HP:0002240	Hepatomegaly
HP:0002630	Fat malabsorption
HP:0002643	Neonatal respiratory distress

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST000253_3	Attention deficit hyperactivity disorder and conduct disorder	6.000000e-06
GCST000520_3	Vitiligo	3.000000e-06
GCST001277_5	Liver enzyme levels (gamma-glutamyl transferase)	9.000000e-10
GCST002690_14	Very long-chain saturated fatty acid levels (fatty acid 20:0)	4.000000e-06
GCST002932_7	Manganese levels	6.000000e-06
GCST007209_20	Gallstone disease	1.000000e-08
GCST008362_65	Birth weight	9.000000e-09
GCST010083_16	Hemoglobin levels	4.000000e-14
GCST011974_11	Lung cancer	4.000000e-06
GCST90002383_90	Hematocrit	2.000000e-13
GCST90002384_438	Hemoglobin	1.000000e-12
GCST90002403_338	Red blood cell count	5.000000e-14
GCST90013405_140	Liver enzyme levels (alanine transaminase)	1.000000e-30
GCST90013407_17	Liver enzyme levels (gamma-glutamyl transferase)	6.000000e-42
GCST90013663_87	Alanine aminotransferase levels	6.000000e-28
GCST90013664_51	Aspartate aminotransferase levels	5.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:0004344	birth weight
EFO:0004509	hemoglobin measurement
EFO:0004348	hematocrit
EFO:0004305	erythrocyte count
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — P4 P-type ATPases: Phospholipid-transporting ATPases

CTD chemical–gene interactions

67 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Estradiol	increases expression, affects expression, affects cotreatment, decreases expression	5
trichostatin A	increases expression, affects cotreatment	4
Air Pollutants	increases abundance, decreases expression	3
Benzo(a)pyrene	decreases expression, increases methylation	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
bisphenol A	decreases expression, decreases methylation	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Progesterone	decreases expression, affects cotreatment	2
Cyclosporine	decreases expression, affects cotreatment	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
beta-lapachone	decreases expression	1
enilconazole	increases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
1-nitropyrene	increases expression	1
triadimefon	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
gadodiamide	increases expression	1
di-n-butylphosphoric acid	affects expression	1

Clinical trials (associated diseases)

28 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03353454	PHASE3	WITHDRAWN	A Placebo-controlled Study of Maralixibat (SHP625) in Pediatric Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC)
NCT03566238	PHASE3	COMPLETED	This Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC Types 1 or 2
NCT03659916	PHASE3	COMPLETED	Long Term Safety & Efficacy Study Evaluating The Effect of A4250 in Children With PFIC
NCT03905330	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Maralixibat in Subjects With Progressive Familial Intrahepatic Cholestasis (MARCH-PFIC)
NCT04185363	PHASE3	COMPLETED	An Extension Study of Maralixibat in Patients With Progressive Familial Intrahepatic Cholestasis (PFIC)
NCT05543187	PHASE3	COMPLETED	A Study of TAK-625 for the Treatment of Progressive Familial Intrahepatic Cholestasis (PFIC)
NCT02057718	PHASE2	COMPLETED	Open Label Study to Evaluate Efficacy and Long Term Safety of LUM001 (Maralixibat) in the Treatment of Cholestatic Liver Disease in Patients With Progressive Familial Intrahepatic Cholestasis
NCT04729751	PHASE2	COMPLETED	A Study to Evaluate the Safety and Tolerability of Maralixibat in Infant Participants With Cholestatic Liver Diseases Including Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille Syndrome (ALGS).
NCT02963077	PHASE1	COMPLETED	A Safety and Pharmakokinetic Study of A4250 Alone or in Combination With A3384
NCT03082937	PHASE1	COMPLETED	An Open Label, Single-dose, Single Period ADME Study of A4250 in Healthy Subjects
NCT03428555	Not specified	UNKNOWN	Integrated Care Pathway for Youth Depression
NCT01784718	Not specified	NO_LONGER_AVAILABLE	Buphenyl Therapy for Byler’s Disease
NCT01949766	Not specified	NO_LONGER_AVAILABLE	Transition From Buphenyl to RAVICTI for the Therapy of Byler Disease
NCT02094222	Not specified	NO_LONGER_AVAILABLE	Expanded Access Protocol for an Intermediate Size Population - RAVICTI for Byler Disease
NCT02131623	Not specified	COMPLETED	Validation of the Itch Reported Outcome (ItchRO) Diaries in Pediatric Cholestatic Liver Disease
NCT03930810	Not specified	ENROLLING_BY_INVITATION	NAtural Course and Prognosis of PFIC and Effect of Biliary Diversion
NCT04071197	Not specified	UNKNOWN	Gastrostomy-Biliary Diversion: Innovative Management for Bile Canalicular Transport Disorders
NCT04483531	Not specified	APPROVED_FOR_MARKETING	Odevixibat for the Treatment of Progressive Familial Intrahepatic Cholestasis
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT05704517	Not specified	UNKNOWN	Progressive Familial Intrahepatic Cholestasis in Indian Children - Establishing an Indian PFIC Registry
NCT06193928	Not specified	RECRUITING	Long-Term SafEty and Clinical Outcomes of LivmArli in Patients in the United States (LEAP-US)
NCT06777914	Not specified	RECRUITING	Familial Intrahepatic Cholestasis-related Genes Associated with Disease Susceptibility in Hepato-biliary Cancers
NCT06778174	Not specified	RECRUITING	Prospective Analysis of the Treatment of Progressive Familial Intrahepatic Cholestasis (TreatFIC)
NCT06781242	Not specified	RECRUITING	Genotype-phenotype Relationship Between Cryptogenic Cholestasis and Familial Intrahepatic Cholestasis
NCT07185919	Not specified	RECRUITING	A Study of the Effectiveness, Safety and the Long-term Outcomes of Participants With Progressive Familial Intrahepatic Cholestasis (PFIC) Who Take Odevixibat (Bylvay) in South Korea
NCT07293897	Not specified	RECRUITING	A Database Study of Maralixibat (TAK-625) in Participants With Alagille Syndrome (ALGS) and Progressive Familial Intrahepatic Cholestasis (PFIC)
NCT07317193	Not specified	RECRUITING	DEFINING THE GENETIC DRIVERS OF ADULT-ONSET CHOLESTATIC LIVER DISEASE
NCT07588880	Not specified	RECRUITING	A Study of the Effectiveness, Safety and the Long-term Outcomes of Participants With Progressive Familial Intrahepatic Cholestasis (PFIC) Who Take Odevixibat (Bylvay) in China