ABCB4

Summary

ABCB4 (ATP binding cassette subfamily B member 4, HGNC:45) is a protein-coding gene on chromosome 7q21.12, encoding Phosphatidylcholine translocator ABCB4 (P21439). Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion. It is haploinsufficient (ClinGen: sufficient evidence).

The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance as well as antigen presentation. This gene encodes a full transporter and member of the p-glycoprotein family of membrane proteins with phosphatidylcholine as its substrate. The function of this protein has not yet been determined; however, it may involve transport of phospholipids from liver hepatocytes into bile. Alternative splicing of this gene results in several products of undetermined function.

Source: NCBI Gene 5244 — RefSeq curated summary.

At a glance

• Gene–disease (curated): progressive familial intrahepatic cholestasis type 3 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 18
• Clinical variants (ClinVar): 1,570 total — 155 pathogenic, 66 likely-pathogenic
• Phenotypes (HPO): 62
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000443

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:45
Approved symbol	ABCB4
Name	ATP binding cassette subfamily B member 4
Location	7q21.12
Locus type	gene with protein product
Status	Approved
Aliases	MDR2, PFIC-3, GBD1
Ensembl gene	ENSG00000005471
Ensembl biotype	protein_coding
OMIM	171060
Entrez	5244

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 30 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000265723, ENST00000359206, ENST00000417608, ENST00000440025, ENST00000453593, ENST00000467079, ENST00000467983, ENST00000469770, ENST00000473795, ENST00000643670, ENST00000644106, ENST00000649586, ENST00000866020, ENST00000866021, ENST00000866022, ENST00000866023, ENST00000866024, ENST00000866025, ENST00000866026, ENST00000866027, ENST00000866028, ENST00000866029, ENST00000866030, ENST00000866031, ENST00000866032, ENST00000866033, ENST00000866034, ENST00000866035, ENST00000939426, ENST00000964815, ENST00000964816, ENST00000964817, ENST00000964818, ENST00000964819, ENST00000964820, ENST00000964821

RefSeq mRNA: 3 — MANE Select: NM_000443 NM_000443, NM_018849, NM_018850

CCDS: CCDS5605, CCDS5606, CCDS5607

Canonical transcript exons

ENST00000649586 — 28 exons

Exon	Start	End
ENSE00000454292	87413617	87413717
ENSE00000454307	87406288	87406494
ENSE00000703052	87452944	87453135
ENSE00000703103	87451623	87451794
ENSE00000703526	87423906	87424052
ENSE00000703613	87411893	87412033
ENSE00000918880	87409236	87409392
ENSE00000918882	87417312	87417515
ENSE00000918883	87418537	87418620
ENSE00000918884	87419998	87420075
ENSE00000918885	87422121	87422225
ENSE00000918890	87440199	87440402
ENSE00000918891	87443319	87443444
ENSE00000918892	87443663	87443773
ENSE00000918893	87444862	87444975
ENSE00000918894	87447034	87447205
ENSE00000918895	87449968	87450092
ENSE00001388379	87475386	87475471
ENSE00001868583	87475634	87475680
ENSE00002486480	87403135	87403281
ENSE00002502499	87439667	87439837
ENSE00002514753	87431404	87431565
ENSE00003567026	87462758	87462908
ENSE00003570234	87472621	87472675
ENSE00003599345	87426750	87426920
ENSE00003611473	87454535	87454592
ENSE00003668484	87408037	87408234
ENSE00003832598	87401696	87402302

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 97.45.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8113 / max 213.5112, expressed in 475 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84720	1.6114	443
84722	0.1138	27
84721	0.0861	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	97.45	gold quality
secondary oocyte	CL:0000655	96.98	gold quality
oocyte	CL:0000023	96.14	gold quality
liver	UBERON:0002107	95.74	gold quality
buccal mucosa cell	CL:0002336	88.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.17	gold quality
right adrenal gland	UBERON:0001233	81.66	gold quality
left adrenal gland	UBERON:0001234	80.81	gold quality
right adrenal gland cortex	UBERON:0035827	80.01	gold quality
left adrenal gland cortex	UBERON:0035825	79.95	gold quality
adrenal gland	UBERON:0002369	79.70	gold quality
biceps brachii	UBERON:0001507	79.24	gold quality
adrenal cortex	UBERON:0001235	79.17	gold quality
spleen	UBERON:0002106	78.91	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	78.88	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.81	gold quality
calcaneal tendon	UBERON:0003701	78.41	gold quality
apex of heart	UBERON:0002098	77.95	gold quality
triceps brachii	UBERON:0001509	76.14	gold quality
ventricular zone	UBERON:0003053	75.88	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	75.35	gold quality
heart left ventricle	UBERON:0002084	74.79	gold quality
cardiac ventricle	UBERON:0002082	74.41	gold quality
lymph node	UBERON:0000029	73.91	gold quality
granulocyte	CL:0000094	73.86	gold quality
right atrium auricular region	UBERON:0006631	73.69	gold quality
tendon	UBERON:0000043	73.58	gold quality
muscle of leg	UBERON:0001383	72.74	gold quality
skeletal muscle tissue	UBERON:0001134	72.28	gold quality
muscle organ	UBERON:0001630	72.27	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1H4, PPARA

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• In addition to PFIC3, ab MDR3 defect can be involved in intrahepatic chlestasis of pregnancy and in cholesterol gallstone disease (PMID:11745043)
• present data indicate that polymorphism of the estrogen receptor alpha gene and multidrug resistance 3 gene mutation are unlikely to play any significant role in obstetric cholestasis in affected Finnish women (PMID:12206920)
• present data indicate that polymorphism of the estrogen receptor alpha and multidrug resistance 3 genes 1712delT mutation are unlikely to play any significant role in obstetric cholestasis in affected Finnish women (PMID:12381474)
• Trp(1242) substitutions markedly alter the substrate specificity of human multidrug resistance protein 3 but leave bile salt binding and transport intact (PMID:12388190)
• sequence variation in women with intrahepatic cholestasis of pregnancy (PMID:12746424)
• MDR3 expression is directly up-regulated by FXR in primary human hepatocytes (PMID:14527955)
• Data do not support a strong role of BSEP and MDR3 genetic variations in the pathogenesis of primary biliary cirrhosis and primary sclerosing cholangitis. (PMID:14999697)
• MDR3 genetic variation is associated with pregnancy-associated cholestasis (PMID:15077010)
• HAX-1 binds bile salt export protein (BSEP), cortactin, MDR1, and MDR2. HAX-1 and cortactin regulate BSEP abundance in the apical membrane of cells. (PMID:15159385)
• BF may enhance the capacity of human hepatocytes to direct PC into bile canaliculi via PPARalpha-mediated redistribution of ABCB4 to the canalicular membrane (PMID:15258199)
• The suppressive effects on MDR3 mRNA of PMA were attenuated in antisense PKCbeta-treated cells, but those in antisense PKCalpha-treated cells were not attenuated. These suggested that PKCbeta plays a regulatory role in the expression of MDR3. (PMID:16854530)
• mutations in the canalicular ABC transporter phospholipid flippase (MDR3) and in the bile salt export pump (BSEP) can predispose for the development of ICP. (PMID:16890614)
• Variants of ABCB4 represent genetic risk factors for the severe form of ICP in Sweden. (PMID:16891356)
• This study demonstrates that splicing mutations in the MDR3 gene can cause intrahepatic cholestasis of pregnancy with normal gamma-GT and may be associated with stillbirths and gallstone disease. (PMID:17187437)
• role of ABCB4 mutations and polymorphisms in drug-induced cholestasis. (PMID:17264802)
• ABCB4 mediates the efflux of phospholipids into the canalicular lumen in the presence of bile salts, and plays a crucial role in bile formation and lipid homeostasis. (PMID:17523162)
• Low phospholipid-associated cholelithiasis (LPAC) is characterized by the association of ABCB4 mutations and low biliary phospholipid concentration with symptomatic and recurring cholelithiasis. (PMID:17562004)
• The molecular characterization of 68 Progressive familial intrahepatic cholestasis type 3 (PFIC3) screened for ABCB4 mutations to date, is reported. (PMID:17726488)
• 48 mutations of MDR3 gene have been reported in humans to date, from which 43 (89.5%) in the coding region, and 5 splice site mutations have been associated to cholesterol cholelithiasis. (PMID:17786139)
• MDR3 mutations are responsible for the development of intrahepatic cholestasis of pregnancy in only a small percentage of Italian women. (PMID:18083082)
• Multidrug resistance induced by cisplatin in ovarian carcinoma cell lines is not due to overexpression of MDR1 and MDR3 genes. (PMID:18231753)
• Heterozygous ABCB4 mutations were detected in 34% of adults with unexplained cholestasis, for the most part without biliary symptoms, and could result in significant liver fibrosis (PMID:18482588)
• The Hap 2/Hap 2 diplotype in MDR3 could therefore be potentially applied to DNA-based diagnosis in Japanese patients with primary biliary cirrhosis (PBC) as a strong genetic biomarker for predicting the progression and prognosis of PBC. (PMID:18671305)
• Mutational analysis of ABCB4 should be generally considered in all patients with cholestatic liver disease of unknown etiology regardless of age and onset of disease. (PMID:18781607)
• Mutations in the ABCB4 gene are a rare cause of gallstone disease. (PMID:19018976)
• Mutation I541F causes mislocalization of both ABCB4 and ABCB1. Intracellular retention of ABCB4-I541F can explain the disease in progressive familial intrahepatic cholestasis type 3 patients bearing this mutation. (PMID:19185004)
• Our study demonstrates the splicing mutations in the ABCB4 gene can cause intrahepatic cholestatis in pregnant women with raised serum gamme-GT. (PMID:19261551)
• Novel mutation in the ABCB4 gene may account for intrahepatic cholestasis of pregnancy. (PMID:19266607)
• The results do not support the hypothesis of a link between ABCB4 and ABCB11 polymorphisms, lithogenic dyslipidemia, and gallstone risk. (PMID:19408031)
• in cystic fibrosis patients the c.834-66G>T adenosine triphospate-binding cassette subfamily B member 4 variant may enhance the activity of the protein and thus exert a protective effect toward liver disease (PMID:19467940)
• Mutations in the ABCB4 gene are associated with intrahepatic cholestasis of pregnancy. (PMID:19584064)
• The results suggested that pregnane X receptor, associated with multiple resistance related protein 3, may play an important role in human colon cancer resistance to chemotherapeutics. (PMID:19593667)
• polymorphism in the ABCB4 gene as a predisposing factor for intrahepatic cholestasis of pregnancy in Greece.(489-91) (PMID:19840247)
• Data shiw that multidrug resistance protein 3 R652G polymorphism is negatively correlated with idiopathic infant cholestasis, and that children with the R652G SNP in Guangxi of China may have reduced susceptibility to infant intrahepatic cholestasis. (PMID:19998509)
• Data suggest that variations in canalicular transporters ABCB11 and ABCB4, known to contribute to genetic predisposition to cholesterol gallstones in adulthood, do not contribute specifically to the aetiology of paediatric idiopathic gallstones. (PMID:20163776)
• Data identified three novel mutations in BSEP, one novel mutation in MDR3, and one heterozygous mutation in ATP8B1 in PFIC patients. (PMID:20414253)
• ABCB4 mutations cause many cholestatic liver disease in humans.[Review] (PMID:20422496)
• 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)
• ABCB4 mutations are responsible for a chronic liver disease in more than one-third of patients with chronic intrahepatic cholestasis and elevated gamma-glutamyl-transpeptidase activity. (PMID:21119540)
• LPAC syndrome is based on a mutation in the ABCB4 gene which codes for MDR3 (multidrug resistance protein 3). (PMID:21161147)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	abcb4	ENSDARG00000010936
mus_musculus	Abcb4	ENSMUSG00000042476
rattus_norvegicus	Abcb1b	ENSRNOG00000066042
caenorhabditis_elegans		WBGENE00001817
caenorhabditis_elegans		WBGENE00001818
caenorhabditis_elegans		WBGENE00003995
caenorhabditis_elegans		WBGENE00004000
caenorhabditis_elegans		WBGENE00004001
caenorhabditis_elegans		WBGENE00004002
caenorhabditis_elegans		WBGENE00004003
caenorhabditis_elegans		WBGENE00004006
caenorhabditis_elegans		WBGENE00004008

Paralogs (10): ABCB5 (ENSG00000004846), ABCB11 (ENSG00000073734), ABCB1 (ENSG00000085563), ABCB6 (ENSG00000115657), ABCB7 (ENSG00000131269), ABCB10 (ENSG00000135776), ABCB9 (ENSG00000150967), TAP1 (ENSG00000168394), ABCB8 (ENSG00000197150), TAP2 (ENSG00000204267)

Protein

Protein identifiers

Phosphatidylcholine translocator ABCB4 — P21439 (reviewed: P21439)

Alternative names: ATP-binding cassette sub-family B member 4, Multidrug resistance protein 3, P-glycoprotein 3

All UniProt accessions (5): P21439, A0A2R8Y291, A0A2R8Y8A1, E7EQI1, H7C0M2

UniProt curated annotations — full annotation on UniProt →

Function. Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion. Functions as a floppase that translocates specifically phosphatidylcholine (PC) from the inner to the outer leaflet of the canalicular membrane bilayer into the canaliculi of hepatocytes. Translocation of PC makes the biliary phospholipids available for extraction into the canaliculi lumen by bile salt mixed micelles and therefore protects the biliary tree from the detergent activity of bile salts. Plays a role in the recruitment of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM) molecules to nonraft membranes and to further enrichment of SM and cholesterol in raft membranes in hepatocytes. Required for proper phospholipid bile formation. Indirectly involved in cholesterol efflux activity from hepatocytes into the canalicular lumen in the presence of bile salts in an ATP-dependent manner. Promotes biliary phospholipid secretion as canaliculi-containing vesicles from the canalicular plasma membrane. In cooperation with ATP8B1, functions to protect hepatocytes from the deleterious detergent activity of bile salts. Does not confer multidrug resistance.

Subunit / interactions. May interact with RACK1. Interacts with HAX1.

Subcellular location. Cell membrane. Apical cell membrane. Membrane raft. Cytoplasm. Cytoplasmic vesicle. Clathrin-coated vesicle.

Post-translational modifications. Phosphorylated. Phosphorylation on Thr-34 is required for PC efflux activity. Phosphorylation occurs on serine and threonine residues in a protein kinase A- or C-dependent manner. May be phosphorylated on Thr-44 and Ser-49. Glycosylated.

Disease relevance. Cholestasis, progressive familial intrahepatic, 3 (PFIC3) [MIM:602347] A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC3 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Cholestasis of pregnancy, intrahepatic 3 (ICP3) [MIM:614972] 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. It causes fetal distress, spontaneous premature delivery and intrauterine death. Patients have spontaneous and progressive disappearance of cholestasis after delivery. Cholestasis results from abnormal biliary transport from the liver into the small intestine. The disease is caused by variants affecting the gene represented in this entry. Gallbladder disease 1 (GBD1) [MIM:600803] One of the major digestive diseases. Gallstones composed of cholesterol (cholelithiasis) are the common manifestations in western countries. Most people with gallstones, however, remain asymptomatic through their lifetimes. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Translocation activity is inhibited by the ATPase inhibitor vanadate and the calcium channel blocker verapamil. Translocation activity is enhanced by the addition of the bile salt taurocholate.

Induction. Up-regulated by PPARA. Up-regulated by compounds that cause peroxisome proliferation, such as fenofibrate (at protein level). Up-regulated by bezafibrate. Up-regulated by compounds that cause peroxisome proliferation, such as fenofibrate, bezafibrate and gemfibrozil.

Similarity. Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P21439-1	1	yes
P21439-2	2
P21439-3	3

RefSeq proteins (3): NP_000434, NP_061337, NP_061338 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003439	ABC_transporter-like_ATP-bd	Domain
IPR003593	AAA+_ATPase	Domain
IPR011527	ABC1_TM_dom	Domain
IPR017871	ABC_transporter-like_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036640	ABC1_TM_sf	Homologous_superfamily
IPR039421	Type_1_exporter	Family

Pfam: PF00005, PF00664

Catalyzed reactions (Rhea), 3 shown:

• a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) + ADP + phosphate + H(+) (RHEA:36439)
• a sphingomyelin(in) + ATP + H2O = a sphingomyelin(out) + ADP + phosphate + H(+) (RHEA:38903)
• a 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphocholine(out) + ADP + phosphate + H(+) (RHEA:66272)

UniProt features (221 total): sequence variant 90, helix 46, strand 25, topological domain 13, transmembrane region 12, mutagenesis site 10, binding site 8, turn 5, domain 4, modified residue 2, glycosylation site 2, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6S7P	ELECTRON MICROSCOPY	3.2
7NIV	ELECTRON MICROSCOPY	3.6
7NIW	ELECTRON MICROSCOPY	3.8
7NIU	ELECTRON MICROSCOPY	4.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21439-F1	83.36	0.48

Antibody-complex structures (SAbDab): 3 — 7NIU, 7NIV, 7NIW

Functional residue map

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

Ligand- & substrate-binding residues (8): 406; 432–437; 477; 536; 1046; 1071–1077; 1124; 1184–1186

Post-translational modifications (2): 27, 34

Glycosylation sites (2): 91, 97

Mutagenesis-validated functional residues (10):

Position	Phenotype
34	does not inhibit efflux activity for pc.
44	reduces efflux activity for pc. does not alter apical membrane location.
49	reduces efflux activity for pc. does not alter apical membrane location.
435	inhibits efflux activity for pc and cholesterol, but does not alter glycosylation and surface expression in the presence
558	loss of floppase activity. strongly reduce the atpase activity.
953	accumulates predominantly in intracellular compartments with only a small fraction at the plasma membrane and inhibits p
985	significantly reduces phosphatidylcholine floppase activity; when associated with q-989 and v-990.
989	significantly reduces phosphatidylcholine floppase activity; when associated with m-985 and v-990.
990	significantly reduces phosphatidylcholine floppase activity; when associated with m-985 and q-989.
1075	inhibits efflux activity for pc and cholesterol, but does not alter glycosylation and surface expression in the presence

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-1989781	PPARA activates gene expression
R-HSA-382556	ABC-family protein mediated transport
R-HSA-5678771	Defective ABCB4 causes PFIC3, ICP3 and GBD1
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-556833	Metabolism of lipids
R-HSA-5619084	ABC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters

MSigDB gene sets: 322 (showing top): GOBP_ACID_SECRETION, GOBP_CELLULAR_RESPONSE_TO_LIPID, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_POSITIVE_REGULATION_OF_STEROL_TRANSPORT, LUCAS_HNF4A_TARGETS_UP, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_REGULATION_OF_MEMBRANE_LIPID_DISTRIBUTION, GOBP_POSITIVE_REGULATION_OF_LIPID_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, KEGG_ABC_TRANSPORTERS, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOBP_LIPID_HOMEOSTASIS, UEDA_PERIFERAL_CLOCK, GOBP_RESPONSE_TO_KETONE

GO Biological Process (11): lipid metabolic process (GO:0006629), positive regulation of cholesterol transport (GO:0032376), bile acid secretion (GO:0032782), phospholipid translocation (GO:0045332), transmembrane transport (GO:0055085), lipid homeostasis (GO:0055088), positive regulation of phospholipid translocation (GO:0061092), response to fenofibrate (GO:1901557), cellular response to bile acid (GO:1903413), positive regulation of phospholipid transport (GO:2001140), lipid transport (GO:0006869)

GO Molecular Function (9): ATP binding (GO:0005524), obsolete phospholipid transporter activity (GO:0005548), ATP hydrolysis activity (GO:0016887), ATPase-coupled transmembrane transporter activity (GO:0042626), phosphatidylcholine floppase activity (GO:0090554), ABC-type transporter activity (GO:0140359), nucleotide binding (GO:0000166), protein binding (GO:0005515), ATPase-coupled intramembrane lipid carrier activity (GO:0140326)

GO Cellular Component (12): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), membrane (GO:0016020), apical plasma membrane (GO:0016324), clathrin-coated vesicle (GO:0030136), membrane raft (GO:0045121), intercellular canaliculus (GO:0046581), extracellular exosome (GO:0070062), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Regulation of lipid metabolism by PPARalpha	1
Transport of small molecules	1
ABC transporter disorders	1
Metabolism of lipids	1
Metabolism	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
ATP-dependent activity	3
phospholipid transport	2
transport	2
cytoplasm	2
primary metabolic process	1
cholesterol transport	1
positive regulation of sterol transport	1
regulation of cholesterol transport	1
monocarboxylic acid transport	1
acid secretion	1
lipid translocation	1
cellular process	1
chemical homeostasis	1
phospholipid translocation	1
positive regulation of cellular component organization	1
regulation of phospholipid translocation	1
positive regulation of phospholipid transport	1
response to ether	1
response to ketone	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
response to bile acid	1
positive regulation of lipid transport	1
regulation of phospholipid transport	1
lipid localization	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
primary active transmembrane transporter activity	1
ATP hydrolysis activity	1
phosphatidylcholine intramembrane carrier activity	1
floppase activity	1
ATPase-coupled transmembrane transporter activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intramembrane lipid carrier activity	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2318 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCB4	ATP8B1	O43520	924
ABCB4	SLC10A2	Q12908	848
ABCB4	CYP7A1	P22680	736
ABCB4	NR1H4	Q96RI1	732
ABCB4	SLC10A1	Q14973	731
ABCB4	NR1I2	O75469	698
ABCB4	GGT1	P19440	683
ABCB4	SLC51A	Q86UW1	649
ABCB4	ABCB1	P08183	637
ABCB4	CYP8B1	Q9UNU6	631
ABCB4	ABCC2	Q92887	628
ABCB4	AKR1D1	P51857	591
ABCB4	NR0B2	Q15466	588
ABCB4	SLCO1A2	P46721	580
ABCB4	SLC51B	Q86UW2	580

IntAct

6 interactions, top by confidence:

A	B	Type	Score
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
TESK1	ABCB4	psi-mi:“MI:0915”(physical association)	0.370
ABCB4	PIGY	psi-mi:“MI:0915”(physical association)	0.370
SAAL1	TMEM223	psi-mi:“MI:0914”(association)	0.350
terD	ABCB4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): ABCB4 (Affinity Capture-RNA), ABCB4 (Cross-Linking-MS (XL-MS)), IFIT5 (Cross-Linking-MS (XL-MS)), ABCB4 (Cross-Linking-MS (XL-MS)), ABCB4 (Cross-Linking-MS (XL-MS)), ABCB1 (Cross-Linking-MS (XL-MS)), ABCB11 (Cross-Linking-MS (XL-MS)), TESK1 (Two-hybrid), PIGY (Two-hybrid)

ESM2 similar proteins: A0A059JJ46, A0A1U8QG99, B5X0E4, B8K1W2, F2PRR1, F2RP52, H6TB12, O70127, O95342, P06795, P08183, P16876, P16877, P21439, P21440, P21447, P21449, P23174, P34712, P34713, P43245, P91660, Q00449, Q00748, Q08201, Q0WML0, Q2M3G0, Q54JR2, Q6Q876, Q6YUU5, Q7FB56, Q8LPK2, Q9C7F2, Q9C7F8, Q9FHF1, Q9FNU2, Q9FWX8, Q9LHD1, Q9LHK4, Q9LJX0

Diamond homologs: A0A059JJ46, A0A059JK44, A0A095C325, A0A0D1BUH6, A0A1U8QG99, A0A1U9YI12, A0A2P1AAV1, A0A348AXX9, A1KF14, B2GUP8, B2KWH4, B5X0E4, B8K1W2, F2PRR1, F2Q5G0, F2RP52, F2RPA4, F2SQT8, F2T1C4, G5EG61, H6TB12, J9VF33, K3VYH8, O53645, O70127, O80725, O95342, P06795, P08183, P0CU83, P16875, P16876, P16877, P21439, P21440, P21447, P21448, P21449, P23174, P34712

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NR1H4	“up-regulates quantity by expression”	ABCB4	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

1570 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	155
Likely pathogenic	66
Uncertain significance	693
Likely benign	398
Benign	82

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1335676	NM_000443.4(ABCB4):c.2858C>A (p.Ala953Asp)	Pathogenic
13686	NM_000443.4(ABCB4):c.394_400del (p.Tyr132fs)	Pathogenic
13688	NM_000443.4(ABCB4):c.1712del (p.Val571fs)	Pathogenic
13693	NM_000443.4(ABCB4):c.1328_1329delinsCAA (p.Gln443fs)	Pathogenic
13694	NM_000443.4(ABCB4):c.2169dup (p.Leu724fs)	Pathogenic
13696	NM_000443.4(ABCB4):c.430C>T (p.Arg144Ter)	Pathogenic
1431360	NM_000443.4(ABCB4):c.2653_2654del (p.Arg884_Asp885insTer)	Pathogenic
1454966	NC_000007.13:g.(?87042913)(87043053_?)del	Pathogenic
1458242	NC_000007.13:g.(?87072615)(87076541_?)del	Pathogenic
1676068	NM_000443.4(ABCB4):c.838C>T (p.Gln280Ter)	Pathogenic
1685491	NM_000443.4(ABCB4):c.984T>G (p.Tyr328Ter)	Pathogenic
2423100	NC_000007.13:g.(?87092054)(87092244_?)del	Pathogenic
2498173	NM_000443.4(ABCB4):c.2200G>T (p.Glu734Ter)	Pathogenic
2571280	NM_000443.4(ABCB4):c.2587_2591delinsATCAGTGTTAAACACTGATTGAAAGTGTGTCTGATC (p.Val863_Val864delinsIleSerValLysHisTer)	Pathogenic
2635175	NM_000443.4(ABCB4):c.286+1G>A	Pathogenic
2687808	NM_000443.4(ABCB4):c.2306_2309del (p.Phe769fs)	Pathogenic
2687810	NM_000443.4(ABCB4):c.3770del (p.Gln1257fs)	Pathogenic
2687811	NM_000443.4(ABCB4):c.1733C>T (p.Ala578Val)	Pathogenic
2687813	NM_000443.4(ABCB4):c.3412del (p.Val1138fs)	Pathogenic
2687815	NM_000443.4(ABCB4):c.1635del (p.Ala546fs)	Pathogenic
2687820	NM_000443.4(ABCB4):c.2864G>T (p.Cys955Phe)	Pathogenic
2687821	NM_000443.4(ABCB4):c.784del (p.Ala262fs)	Pathogenic
2695513	NM_000443.4(ABCB4):c.3520C>T (p.Gln1174Ter)	Pathogenic
2713948	NM_000443.4(ABCB4):c.749del (p.Ala250fs)	Pathogenic
2735040	NM_000443.4(ABCB4):c.3349C>T (p.Gln1117Ter)	Pathogenic
2735041	NM_000443.4(ABCB4):c.1768C>T (p.Arg590Ter)	Pathogenic
2737106	NM_000443.4(ABCB4):c.3492T>G (p.Tyr1164Ter)	Pathogenic
2758037	NM_000443.4(ABCB4):c.2090_2093dup (p.Lys699fs)	Pathogenic
2777505	NM_000443.4(ABCB4):c.1690_1702del (p.Asp564fs)	Pathogenic
2820526	NM_000443.4(ABCB4):c.2609C>G (p.Ser870Ter)	Pathogenic

SpliceAI

4074 predictions. Top by Δscore:

Variant	Effect	Δscore
7:87403133:A:T	donor_loss	1.0000
7:87403134:C:CA	donor_loss	1.0000
7:87403134:CCTTT:C	donor_gain	1.0000
7:87403279:TTT:T	acceptor_gain	1.0000
7:87406286:A:AC	donor_gain	1.0000
7:87406287:C:CC	donor_gain	1.0000
7:87406495:C:CC	acceptor_gain	1.0000
7:87409234:A:AC	donor_gain	1.0000
7:87409234:ACAGG:A	donor_gain	1.0000
7:87409235:C:CC	donor_gain	1.0000
7:87409235:CAGG:C	donor_gain	1.0000
7:87409235:CAGGC:C	donor_gain	1.0000
7:87409389:CACC:C	acceptor_gain	1.0000
7:87409391:CC:C	acceptor_gain	1.0000
7:87409392:CC:C	acceptor_gain	1.0000
7:87418535:A:AC	donor_gain	1.0000
7:87418535:ACT:A	donor_gain	1.0000
7:87418536:C:CC	donor_gain	1.0000
7:87418536:CTC:C	donor_gain	1.0000
7:87426748:A:AC	donor_gain	1.0000
7:87426749:C:CC	donor_gain	1.0000
7:87426749:CAA:C	donor_gain	1.0000
7:87426749:CAAGT:C	donor_gain	1.0000
7:87431399:AGTAC:A	donor_loss	1.0000
7:87431400:GTAC:G	donor_loss	1.0000
7:87431401:TACCT:T	donor_loss	1.0000
7:87431402:A:AT	donor_loss	1.0000
7:87431403:C:CT	donor_loss	1.0000
7:87431435:T:A	donor_gain	1.0000
7:87431561:CTGGC:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000088915 (7:87389713 T>A,C), RS1000094533 (7:87421626 A>C), RS1000105079 (7:87455664 C>A), RS1000137774 (7:87455197 A>G), RS1000183408 (7:87418183 C>T), RS1000195002 (7:87427140 G>T), RS1000198256 (7:87368314 T>A), RS1000198773 (7:87377287 A>G), RS1000212936 (7:87418622 T>C), RS1000226693 (7:87471063 T>C), RS1000287343 (7:87434350 T>C), RS1000326261 (7:87477366 T>A), RS1000378315 (7:87472880 A>G), RS1000391993 (7:87433675 GTTTTTTT>G,GT,GTTT,GTTTT,GTTTTT,GTTTTTT,GTTTTTTTT,GTTTTTTTTT,GTTTTTTTTTT,GTTTTTTTTTTT,GTTTTTTTTTTTT,GTTTTTTTTTTTTT,GTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTT), RS1000525296 (7:87420049 C>T)

Disease associations

OMIM: gene MIM:171060 | disease phenotypes: MIM:602347, MIM:600803, MIM:614972, MIM:211600, MIM:181500, MIM:248200

GenCC curated gene-disease

Disease	Classification	Inheritance
gallbladder disease 1	Definitive	Semidominant
progressive familial intrahepatic cholestasis type 3	Strong	Autosomal recessive
cholestasis, intrahepatic, of pregnancy, 3	Strong	Semidominant
pancreatitis	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
progressive familial intrahepatic cholestasis type 3	Definitive	AR

Mondo (10): progressive familial intrahepatic cholestasis type 3 (MONDO:0011214), gallbladder disease 1 (MONDO:0010939), familial intrahepatic cholestasis (MONDO:0017290), cholestasis, intrahepatic, of pregnancy, 3 (MONDO:0013995), progressive familial intrahepatic cholestasis (MONDO:0015762), progressive familial intrahepatic cholestasis type 1 (MONDO:0008892), schizophrenia (MONDO:0005090), intrahepatic cholestasis (MONDO:0019072), severe early-childhood-onset retinal dystrophy (MONDO:0009549), pancreatitis (MONDO:0004982)

Orphanet (9): Progressive familial intrahepatic cholestasis type 3 (Orphanet:79305), Familial intrahepatic cholestasis (Orphanet:284385), Low phospholipid-associated cholelithiasis (Orphanet:69663), Intrahepatic cholestasis of pregnancy (Orphanet:69665), Progressive familial intrahepatic cholestasis (Orphanet:172), Progressive familial intrahepatic cholestasis type 1 (Orphanet:79306), Severe early-childhood-onset retinal dystrophy (Orphanet:364055), Stargardt disease (Orphanet:827), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

62 total (30 of 62 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000716	Depression
HP:0000819	Diabetes mellitus
HP:0000821	Hypothyroidism
HP:0000822	Hypertension
HP:0000952	Jaundice
HP:0000988	Skin rash
HP:0000989	Pruritus
HP:0001081	Cholelithiasis
HP:0001082	Cholecystitis
HP:0001337	Tremor
HP:0001394	Cirrhosis
HP:0001395	Hepatic fibrosis
HP:0001396	Cholestasis
HP:0001402	Hepatocellular carcinoma
HP:0001406	Intrahepatic cholestasis
HP:0001408	Bile duct proliferation
HP:0001513	Obesity
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:0002613	Biliary cirrhosis

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST002576_6	Epithelial ovarian cancer	4.000000e-06
GCST004201_1	Gallbladder cancer	2.000000e-10
GCST005998_17	Alanine transaminase levels	2.000000e-18
GCST006612_58	LDL cholesterol	7.000000e-10
GCST006614_40	Total cholesterol levels	2.000000e-08
GCST007209_24	Gallstone disease	9.000000e-28
GCST010204_55	Low density lipoprotein cholesterol levels	6.000000e-09
GCST010243_134	Apolipoprotein B levels	4.000000e-09
GCST010245_26	LDL cholesterol levels	7.000000e-09
GCST011352_28	Alanine aminotransferase levels	1.000000e-19
GCST90002385_141	High light scatter reticulocyte count	1.000000e-09
GCST90002386_452	High light scatter reticulocyte percentage of red cells	2.000000e-09
GCST90002396_394	Mean reticulocyte volume	3.000000e-11
GCST90002404_293	Red cell distribution width	1.000000e-10
GCST90002405_483	Reticulocyte count	8.000000e-12
GCST90002406_249	Reticulocyte fraction of red cells	1.000000e-11
GCST90011898_104	Alanine aminotransferase levels	4.000000e-42
GCST90011899_133	Aspartate aminotransferase levels	3.000000e-12

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0007986	reticulocyte count
EFO:0010701	mean reticulocyte volume
EFO:0009188	Red cell distribution width
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002780	Cholestasis, Intrahepatic	C06.130.120.135.250; C06.552.150
D010195	Pancreatitis	C06.689.750
C535935	Cholestasis, progressive familial intrahepatic 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1743129 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 68 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL4297270	BMS-986020	2	68

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1149222	Toxicity	4	anthracyclines and related substances	Neoplasms
rs1202283	Efficacy	3	imatinib	Gastrointestinal Stromal Tumors
rs4148808	Toxicity	4	anthracyclines and related substances	Neoplasms

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1149222	ABCB4	4	-1.00	1	anthracyclines and related substances
rs4148808	ABCB4	4	-1.50	1	anthracyclines and related substances
rs1202283	ABCB4	3	2.50	1	imatinib

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — ABCB subfamily

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.12	IC50	7500	nM	BMS-986020
5.10	IC50	7943	nM	BMS-986020

PubChem BioAssay actives

1 with measured affinity, of 8 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[4-[4-[3-methyl-4-[[(1R)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]cyclopropane-1-carboxylic acid	1813448: Inhibition of MDR3 (unknown origin)	ic50	7.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases activity, decreases methylation, affects cotreatment, increases expression, affects expression	9
Chenodeoxycholic Acid	affects cotreatment, increases expression, affects binding, increases activity, decreases expression	6
Cyclosporine	decreases expression, increases expression, affects cotreatment	6
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	4
Acetaminophen	decreases expression, affects cotreatment	3
Doxorubicin	decreases reaction, increases expression, decreases response to substance	3
Phospholipids	affects localization, affects transport	3
Aflatoxin B1	increases expression, decreases methylation, affects expression, affects cotreatment	3
nefazodone	affects cotreatment, increases expression, decreases activity	2
zafirlukast	decreases activity	2
GW 4064	affects binding, increases activity, increases expression	2
Troglitazone	decreases activity, increases expression	2
Bezafibrate	affects localization, affects cotreatment, increases expression, affects reaction	2
Deoxycholic Acid	affects cotreatment, decreases expression, increases expression	2
Diclofenac	decreases activity, decreases expression	2
Glycochenodeoxycholic Acid	increases expression, affects cotreatment, decreases expression	2
Glycocholic Acid	affects cotreatment, decreases expression, increases expression	2
Glycodeoxycholic Acid	affects cotreatment, decreases expression, increases expression	2
Gold	decreases expression, affects binding	2
Methapyrilene	decreases expression, decreases methylation	2
Methotrexate	decreases activity, increases expression	2
Verapamil	decreases activity, decreases expression	2
Ritonavir	decreases activity, decreases expression	2
bisphenol F	increases methylation, affects cotreatment	1
benzarone	decreases activity	1
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
oxybutynin	decreases activity	1
triphenyl phosphate	affects expression	1
chlortoluron	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 3 admet, 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1743163	ADMET	Substrates of transporters of clinical importance in the absorption and disposition of drugs, MDR3	Membrane transporters in drug development. — Nat Rev Drug Discov
CHEMBL6158908	Binding	Inhibition of MDR3 in human hepatocytes in the presence of TCA incubated for 3 hrs by LC-MS/MS	Novel Cyclohexyl Amido Acid Antagonists of Lysophosphatidic Acid Type 1 Receptor for the Treatment of Pulmonary Fibrosis. — ACS Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B6AF	HepaRG MDR3 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00318994	PHASE4	COMPLETED	Evaluation of Pancreatic Tissue Penetration of Meronem® in the Prophylaxis of Septic Complications in Severe Pancreatitis
NCT00428025	PHASE4	TERMINATED	Diclofenac for the Prevention of Post-ERCP Pancreatitis in Higher Risk Patients
NCT00786929	PHASE4	COMPLETED	Acute Pancreatitis and Acute Fluid Collections
NCT00999232	PHASE4	COMPLETED	Assess the Effect of Erythromycin on the Rate of Success in Placement of a Self-propelled Feeding Tube
NCT01070680	PHASE4	COMPLETED	Dexmedetomidine Versus Placebo in Endoscopic Retrograde Cholangiopancreatography (ERCP) Sedation
NCT01132521	PHASE4	SUSPENDED	Ulinastatin in Severe Acute Pancreatitis
NCT01186562	PHASE4	COMPLETED	Sitagliptin Therapy to Improve Outcomes After Islet Autotransplant
NCT01744847	PHASE4	COMPLETED	DGT Versus TPS in Patients With Initial PD Cannulation by Chance; Prospective Multi-center Study
NCT01784445	PHASE4	COMPLETED	Post ERCP Pancreatitis Prevention in Average Risk Patients
NCT02027311	PHASE4	COMPLETED	Etomidate vs. Midazolam for Sedation During ERCP
NCT02281799	PHASE4	WITHDRAWN	Thiopurine Induced Pancreatitis in IBD Patients
NCT02465138	PHASE4	WITHDRAWN	A Randomized Controlled Trial of IV Ketorolac to Prevent Post-ERCP Pancreatitis
NCT02797067	PHASE4	COMPLETED	Rectal Indomethacin to Prevent Post ESWL-pancreatitis
NCT05659147	PHASE4	ENROLLING_BY_INVITATION	Imaging Biomarkers of Pancreatic Function and Disease
NCT07024199	PHASE4	RECRUITING	Comparison of the Effectiveness of Paracetamol With Ibuprofen or Paracetamol With Metamizole in Treating Pain in Acute Pancreatitis in Children
NCT07083063	PHASE4	RECRUITING	Precise Endoscopic Application of Nitroglycerin in Preventing Post-ERCP Pancreatitis
NCT07262957	PHASE4	RECRUITING	Preventing Postoperative Complications in Patients Undergoing High-risk Pancreatoduodenectomy With a Bundle Approach Including Hydrocortisone, Octreotide, and the Teres Ligament Patch (PANENCA)
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder