ABCB4

The ATP-binding cassette 4 (ABCB4) gene encodes multidrug resistance protein 3. ABCB4 is associated with progressive familial intrahepatic cholestasis type 3 and intrahepatic cholestasis of pregnancy.

ABCB4
Identifiers
Aliases	ABCB4, ABC21, GBD1, ICP3, MDR2, MDR2/3, MDR3, PFIC-3, PGY3, ATP binding cassette subfamily B member 4
External IDs	OMIM: 171060; MGI: 97569; HomoloGene: 136368; GeneCards: ABCB4; OMA:ABCB4 - orthologs
EC number	7.6.2.2
Gene location (Human) Chr. Chromosome 7 (human) Band 7q21.12 Start 87,401,696 bp End 87,480,435 bp
Gene location (Mouse) Chr. Chromosome 5 (mouse) Band 5 A1|5 3.43 cM Start 8,943,717 bp End 9,009,231 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver secondary oocyte buccal mucosa cell testicle right adrenal gland left adrenal gland right adrenal cortex left adrenal cortex biceps brachii spleen Top expressed in left lobe of liver tibialis anterior muscle vastus lateralis muscle extensor digitorum longus muscle plantaris muscle tibiofemoral joint ankle gastrocnemius muscle muscle of thigh triceps brachii muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function ATPase-coupled transmembrane transporter activity nucleotide binding ABC-type xenobiotic transporter activity phosphatidylcholine transporter activity phosphatidylcholine floppase activity ATPase activity protein binding hydrolase activity ATP binding phospholipid transporter activity ceramide floppase activity Cellular component cytoplasm integral component of membrane membrane plasma membrane integral component of plasma membrane intercellular canaliculus apical plasma membrane membrane raft extracellular exosome cytoplasmic vesicle clathrin-coated vesicle nucleoplasm cytosol focal adhesion actin cytoskeleton brush border membrane apical part of cell Biological process lipid transport cellular response to bile acid positive regulation of cholesterol transport positive regulation of phospholipid translocation xenobiotic transmembrane transport lipid metabolism positive regulation of phospholipid transport response to fenofibrate xenobiotic transport transmembrane transport lipid homeostasis bile acid secretion phospholipid translocation response to hypoxia placenta development brain development lactation circadian rhythm hormone transport response to organic substance response to mycotoxin response to organic cyclic compound response to isoquinoline alkaloid response to nutrient levels response to estradiol response to vitamin A carbohydrate export response to vitamin D maintenance of blood-brain barrier cellular response to mycotoxin daunorubicin transport response to morphine xenobiotic export response to cadmium ion intestinal absorption negative regulation of cell death establishment of blood-brain barrier cellular response to external biotic stimulus cellular response to antibiotic cellular response to alkaloid cellular response to estradiol stimulus cellular response to organic cyclic compound cellular hyperosmotic salinity response response to dexamethasone cellular response to dexamethasone stimulus response to thyroxine response to antineoplastic agent ceramide translocation response to L-glutamate response to glycoside cellular response to borneol cellular response to L-glutamate response to codeine response to quercetin response to cyclosporin A xenobiotic transport across blood-brain barrier establishment of blood-retinal barrier positive regulation of response to drug regulation of lipid metabolic process regulation of intestinal absorption transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5244 18670 Ensembl ENSG00000005471 ENSMUSG00000042476 UniProt P21439 P21440 RefSeq (mRNA) NM_000443 NM_018849 NM_018850 NM_008830 RefSeq (protein) NP_000434 NP_061337 NP_061338 NP_032856 Location (UCSC) Chr 7: 87.4 – 87.48 Mb Chr 5: 8.94 – 9.01 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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 (flippase activity). 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.

Cancer

ABCB4 gene has been observed progressively downregulated in human papillomavirus-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy. For this reason, ABCB4 is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical preneoplastic lesions progression.

Other conditions that have been associated with mutations in this gene include low phospholipid associated cholelithiasis syndrome, high gamma glutamyl transferase intrahepatic cholestasis of pregnancy, chronic cholangiopathy and adult biliary fibrosis.

Further reading

• Rosmorduc O, Poupon R (2007). "Low phospholipid associated cholelithiasis: association with mutation in the MDR3/ABCB4 gene". Orphanet Journal of Rare Diseases. 2: 29. doi:10.1186/1750-1172-2-29. PMC 1910597. PMID 17562004.
• Mbongo-Kama E, Harnois F, Mennecier D, et al. (2007). "MDR3 mutations associated with intrahepatic and gallbladder cholesterol cholelithiasis: an update". Annals of Hepatology. 6 (3): 143–9. doi:10.1016/S1665-2681(19)31919-2. PMID 17786139.
• Lincke CR, Smit JJ, van der Velde-Koerts T, Borst P (1991). "Structure of the human MDR3 gene and physical mapping of the human MDR locus". J. Biol. Chem. 266 (8): 5303–10. doi:10.1016/S0021-9258(19)67788-4. PMID 2002063.
• van der Bliek AM, Kooiman PM, Schneider C, Borst P (1989). "Sequence of mdr3 cDNA encoding a human P-glycoprotein". Gene. 71 (2): 401–11. doi:10.1016/0378-1119(88)90057-1. PMID 2906314.
• Callen DF, Baker E, Simmers RN, et al. (1987). "Localization of the human multiple drug resistance gene, MDR1, to 7q21.1". Hum. Genet. 77 (2): 142–4. doi:10.1007/BF00272381. PMID 3477522. S2CID 40453462.
• Smit JJ, Schinkel AH, Mol CA, et al. (1994). "Tissue distribution of the human MDR3 P-glycoprotein". Lab. Invest. 71 (5): 638–49. PMID 7734012.
• Smit JJ, Mol CA, van Deemter L, et al. (1995). "Characterization of the promoter region of the human MDR3 P-glycoprotein gene". Biochim. Biophys. Acta. 1261 (1): 44–56. doi:10.1016/0167-4781(94)00214-n. PMID 7893760.
• Whitington PF, Freese DK, Alonso EM, et al. (1994). "Clinical and biochemical findings in progressive familial intrahepatic cholestasis". J. Pediatr. Gastroenterol. Nutr. 18 (2): 134–41. doi:10.1097/00005176-199402000-00003. PMID 7912266. S2CID 41477311.
• Ruetz S, Gros P (1994). "Phosphatidylcholine translocase: a physiological role for the mdr2 gene". Cell. 77 (7): 1071–81. doi:10.1016/0092-8674(94)90446-4. PMID 7912658. S2CID 35251756.
• Smit JJ, Schinkel AH, Oude Elferink RP, et al. (1993). "Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease". Cell. 75 (3): 451–62. doi:10.1016/0092-8674(93)90380-9. PMID 8106172. S2CID 29083916.
• van Helvoort A, Smith AJ, Sprong H, et al. (1996). "MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine". Cell. 87 (3): 507–17. doi:10.1016/S0092-8674(00)81370-7. PMID 8898203. S2CID 16488.
• de Vree JM, Jacquemin E, Sturm E, et al. (1998). "Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis". Proceedings of the National Academy of Sciences of the United States of America. 95 (1): 282–7. Bibcode:1998PNAS...95..282D. doi:10.1073/pnas.95.1.282. PMC 18201. PMID 9419367.
• Malorni W, Lucia MB, Rainaldi G, et al. (1998). "Intracellular expression of P-170 glycoprotein in peripheral blood mononuclear cell subsets from healthy donors and HIV-infected patients". Haematologica. 83 (1): 13–20. PMID 9542318.
• Jacquemin E, Cresteil D, Manouvrier S, et al. (1999). "Heterozygous non-sense mutation of the MDR3 gene in familial intrahepatic cholestasis of pregnancy". Lancet. 353 (9148): 210–1. doi:10.1016/S0140-6736(05)77221-4. PMID 9923886. S2CID 31374153.
• Dixon PH, Weerasekera N, Linton KJ, et al. (2000). "Heterozygous MDR3 missense mutation associated with intrahepatic cholestasis of pregnancy: evidence for a defect in protein trafficking". Hum. Mol. Genet. 9 (8): 1209–17. doi:10.1093/hmg/9.8.1209. PMID 10767346.
• Jacquemin E (2002). "Role of multidrug resistance 3 deficiency in pediatric and adult liver disease: one gene for three diseases". Semin. Liver Dis. 21 (4): 551–62. doi:10.1055/s-2001-19033. PMID 11745043. S2CID 28265904.
• Eloranta ML, Heiskanen JT, Hiltunen MJ, et al. (2003). "Multidrug resistance 3 gene mutation 1712delT and estrogen receptor alpha gene polymorphisms in Finnish women with obstetric cholestasis". Eur. J. Obstet. Gynecol. Reprod. Biol. 104 (2): 109–12. doi:10.1016/S0301-2115(02)00064-7. PMID 12206920.
• Eloranta ML, Heiskanen JT, Hiltunen MJ, et al. (2003). "Multidrug resistance 3 gene mutation 1712delT and estrogen receptor alpha gene polymorphisms in Finnish women with obstetric cholestasis". Eur. J. Obstet. Gynecol. Reprod. Biol. 105 (2): 132–5. doi:10.1016/s0301-2115(02)00160-4. PMID 12381474.

External links

• ABCB4+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• ABCB4 human gene location in the UCSC Genome Browser.
• ABCB4 human gene details in the UCSC Genome Browser.