ABCC6

Summary

Gene Symbol: ABCC6
Description: ATP binding cassette subfamily C member 6
Alias: ABC34, ARA, EST349056, GACI2, MLP1, MOAT-E, MOATE, MRP6, PXE, PXE1, URG7, multidrug resistance-associated protein 6, URG7 protein, ATP-binding cassette, sub-family C (CFTR/MRP), member 6, anthracycline resistance-associated protein, multi-specific organic anion transporter E
Species: human
Products:     ABCC6

Top Publications

  1. Jansen R, Küçükosmanoglu A, de Haas M, Sapthu S, Otero J, Hegman I, et al. ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release. Proc Natl Acad Sci U S A. 2013;110:20206-11 pubmed publisher
    ..PXE is caused by inactivating mutations in the gene encoding ATP-binding cassette sub-family C member 6 (ABCC6), an ATP-dependent efflux transporter present mainly in the liver...
  2. Fülöp K, Jiang Q, Wetering K, Pomozi V, Szabó P, Arányi T, et al. ABCC6 does not transport vitamin K3-glutathione conjugate from the liver: relevance to pathomechanisms of pseudoxanthoma elasticum. Biochem Biophys Res Commun. 2011;415:468-71 pubmed publisher
    ..It has been suggested that ABCC6 may have a role in transporting vitamin K or its derivatives from the liver to the periphery...
  3. Le Saux O, Urban Z, Tschuch C, Csiszar K, Bacchelli B, Quaglino D, et al. Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Nat Genet. 2000;25:223-7 pubmed
    ..Here we report the exclusion of five of these genes and the identification of the first mutations responsible for the development of PXE in a gene encoding a protein associated with multidrug resistance (ABCC6).
  4. Uitto J, Pulkkinen L, Ringpfeil F. Molecular genetics of pseudoxanthoma elasticum: a metabolic disorder at the environment-genome interface?. Trends Mol Med. 2001;7:13-7 pubmed
    ..Recently, PXE has been linked to mutations in the MRP6/ABCC6 gene, a member of the ABC transporter family, expressed primarily in the liver and the kidneys...
  5. Schulz V, Hendig D, Szliska C, Gotting C, Kleesiek K. Novel mutations in the ABCC6 gene of German patients with pseudoxanthoma elasticum. Hum Biol. 2005;77:367-84 pubmed
    ..Recently, the PXE candidate gene ABCC6 was identified and a limited number of ABCC6 mutations were observed in different PXE cohorts...
  6. Uitto J. The gene family of ABC transporters--novel mutations, new phenotypes. Trends Mol Med. 2005;11:341-3 pubmed
    ..Recently, mutations in two ABC-transporter genes, ABCC6 and ABCA12, have been demonstrated to underlie phenotypically different diseases affecting the skin (..
  7. Li Q, Grange D, Armstrong N, Whelan A, Hurley M, Rishavy M, et al. Mutations in the GGCX and ABCC6 genes in a family with pseudoxanthoma elasticum-like phenotypes. J Invest Dermatol. 2009;129:553-63 pubmed publisher
    ..feature of classic pseudoxanthoma elasticum (PXE), an autosomal recessive disorder caused by mutations in the ABCC6 gene, is aberrant mineralization of connective tissues, particularly the elastic fibers...
  8. Hu X, Peek R, Plomp A, ten Brink J, Scheffer G, van Soest S, et al. Analysis of the frequent R1141X mutation in the ABCC6 gene in pseudoxanthoma elasticum. Invest Ophthalmol Vis Sci. 2003;44:1824-9 pubmed
    To characterize the ABCC6 R1141X nonsense mutation, which is implicated in more than 25% of a cohort of patients from The Netherlands with pseudoxanthoma elasticum (PXE)...
  9. Uitto J, Li Q, Jiang Q. Pseudoxanthoma elasticum: molecular genetics and putative pathomechanisms. J Invest Dermatol. 2010;130:661-70 pubmed publisher
    ..The classic forms of PXE are due to loss-of-function mutations in the ABCC6 gene, which encodes ABCC6, a transmembrane efflux transporter expressed primarily in the liver...
  10. Trip M, Smulders Y, Wegman J, Hu X, Boer J, ten Brink J, et al. Frequent mutation in the ABCC6 gene (R1141X) is associated with a strong increase in the prevalence of coronary artery disease. Circulation. 2002;106:773-5 pubmed
    ..Recently, we and others have identified mutations in the gene coding for the ABCC6 transporter in PXE patients with ocular and skin involvement...

Detail Information

Publications62

  1. Jansen R, Küçükosmanoglu A, de Haas M, Sapthu S, Otero J, Hegman I, et al. ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release. Proc Natl Acad Sci U S A. 2013;110:20206-11 pubmed publisher
    ..PXE is caused by inactivating mutations in the gene encoding ATP-binding cassette sub-family C member 6 (ABCC6), an ATP-dependent efflux transporter present mainly in the liver...
  2. Fülöp K, Jiang Q, Wetering K, Pomozi V, Szabó P, Arányi T, et al. ABCC6 does not transport vitamin K3-glutathione conjugate from the liver: relevance to pathomechanisms of pseudoxanthoma elasticum. Biochem Biophys Res Commun. 2011;415:468-71 pubmed publisher
    ..It has been suggested that ABCC6 may have a role in transporting vitamin K or its derivatives from the liver to the periphery...
  3. Le Saux O, Urban Z, Tschuch C, Csiszar K, Bacchelli B, Quaglino D, et al. Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Nat Genet. 2000;25:223-7 pubmed
    ..Here we report the exclusion of five of these genes and the identification of the first mutations responsible for the development of PXE in a gene encoding a protein associated with multidrug resistance (ABCC6).
  4. Uitto J, Pulkkinen L, Ringpfeil F. Molecular genetics of pseudoxanthoma elasticum: a metabolic disorder at the environment-genome interface?. Trends Mol Med. 2001;7:13-7 pubmed
    ..Recently, PXE has been linked to mutations in the MRP6/ABCC6 gene, a member of the ABC transporter family, expressed primarily in the liver and the kidneys...
  5. Schulz V, Hendig D, Szliska C, Gotting C, Kleesiek K. Novel mutations in the ABCC6 gene of German patients with pseudoxanthoma elasticum. Hum Biol. 2005;77:367-84 pubmed
    ..Recently, the PXE candidate gene ABCC6 was identified and a limited number of ABCC6 mutations were observed in different PXE cohorts...
  6. Uitto J. The gene family of ABC transporters--novel mutations, new phenotypes. Trends Mol Med. 2005;11:341-3 pubmed
    ..Recently, mutations in two ABC-transporter genes, ABCC6 and ABCA12, have been demonstrated to underlie phenotypically different diseases affecting the skin (..
  7. Li Q, Grange D, Armstrong N, Whelan A, Hurley M, Rishavy M, et al. Mutations in the GGCX and ABCC6 genes in a family with pseudoxanthoma elasticum-like phenotypes. J Invest Dermatol. 2009;129:553-63 pubmed publisher
    ..feature of classic pseudoxanthoma elasticum (PXE), an autosomal recessive disorder caused by mutations in the ABCC6 gene, is aberrant mineralization of connective tissues, particularly the elastic fibers...
  8. Hu X, Peek R, Plomp A, ten Brink J, Scheffer G, van Soest S, et al. Analysis of the frequent R1141X mutation in the ABCC6 gene in pseudoxanthoma elasticum. Invest Ophthalmol Vis Sci. 2003;44:1824-9 pubmed
    To characterize the ABCC6 R1141X nonsense mutation, which is implicated in more than 25% of a cohort of patients from The Netherlands with pseudoxanthoma elasticum (PXE)...
  9. Uitto J, Li Q, Jiang Q. Pseudoxanthoma elasticum: molecular genetics and putative pathomechanisms. J Invest Dermatol. 2010;130:661-70 pubmed publisher
    ..The classic forms of PXE are due to loss-of-function mutations in the ABCC6 gene, which encodes ABCC6, a transmembrane efflux transporter expressed primarily in the liver...
  10. Trip M, Smulders Y, Wegman J, Hu X, Boer J, ten Brink J, et al. Frequent mutation in the ABCC6 gene (R1141X) is associated with a strong increase in the prevalence of coronary artery disease. Circulation. 2002;106:773-5 pubmed
    ..Recently, we and others have identified mutations in the gene coding for the ABCC6 transporter in PXE patients with ocular and skin involvement...
  11. Le Saux O, Beck K, Sachsinger C, Silvestri C, Treiber C, Göring H, et al. A spectrum of ABCC6 mutations is responsible for pseudoxanthoma elasticum. Am J Hum Genet. 2001;69:749-64 pubmed
    ..pseudoxanthoma elasticum (PXE), we performed a mutational analysis of ATP-binding cassette subfamily C member 6 (ABCC6) in 122 unrelated patients with PXE, the largest cohort of patients yet studied...
  12. Belinsky M, Kruh G. MOAT-E (ARA) is a full-length MRP/cMOAT subfamily transporter expressed in kidney and liver. Br J Cancer. 1999;80:1342-9 pubmed
    ..In the present study we describe the fourth MRP/cMOAT-related transporter. We analysed ARA, a human cDNA reported to encode a 453 residue MRP-related transporter, and found that it represents a fused ..
  13. Jansen R, Duijst S, Mahakena S, Sommer D, Szeri F, Varadi A, et al. ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report. Arterioscler Thromb Vasc Biol. 2014;34:1985-9 pubmed publisher
    Mutations in ABCC6 underlie the ectopic mineralization disorder pseudoxanthoma elasticum (PXE) and some forms of generalized arterial calcification of infancy, both of which affect the cardiovascular system...
  14. Finger R, Charbel Issa P, Ladewig M, Gotting C, Szliska C, Scholl H, et al. Pseudoxanthoma elasticum: genetics, clinical manifestations and therapeutic approaches. Surv Ophthalmol. 2009;54:272-85 pubmed publisher
    ..Its prevalence has been estimated to be 1:25,000-100,000. Very recently, the ABCC6 gene on chromosome 16p13.1 was found to be associated with the disease...
  15. de Boussac H, Ratajewski M, Sachrajda I, Koblos G, Tordai A, Pulaski L, et al. The ERK1/2-hepatocyte nuclear factor 4alpha axis regulates human ABCC6 gene expression in hepatocytes. J Biol Chem. 2010;285:22800-8 pubmed publisher
    b>ABCC6 mutations are responsible for the development of pseudoxanthoma elasticum, a rare recessive disease characterized by calcification of elastic fibers...
  16. Pomozi V, Le Saux O, Brampton C, Apana A, Iliás A, Szeri F, et al. ABCC6 is a basolateral plasma membrane protein. Circ Res. 2013;112:e148-51 pubmed publisher
    b>ABCC6 plays a crucial role in ectopic calcification; mutations of the gene cause pseudoxanthoma elasticum and general arterial calcification of infancy...
  17. Kool M, Van der Linden M, de Haas M, Baas F, Borst P. Expression of human MRP6, a homologue of the multidrug resistance protein gene MRP1, in tissues and cancer cells. Cancer Res. 1999;59:175-82 pubmed
    ..encoding the canalicular multispecific organic anion transporter; and four homologues, called MRP3, MRP4, MRP5, and MRP6. The most recently discovered member of the family, MRP6, is analyzed in this report...
  18. Bergen A, Plomp A, Schuurman E, Terry S, Breuning M, Dauwerse H, et al. Mutations in ABCC6 cause pseudoxanthoma elasticum. Nat Genet. 2000;25:228-31 pubmed
    ..Here we describe homozygosity mapping in five PXE families and the detection of deletions or mutations in ABCC6 (formerly MRP6) associated with all genetic forms of PXE in seven patients or families.
  19. Hu X, Plomp A, Wijnholds J, Ten Brink J, van Soest S, van den Born L, et al. ABCC6/MRP6 mutations: further insight into the molecular pathology of pseudoxanthoma elasticum. Eur J Hum Genet. 2003;11:215-24 pubmed
    ..Recently, we and others showed that PXE is caused by mutations in the ABCC6/MRP6 gene...
  20. Le Saux O, Bunda S, VanWart C, Douet V, Got L, Martin L, et al. Serum factors from pseudoxanthoma elasticum patients alter elastic fiber formation in vitro. J Invest Dermatol. 2006;126:1497-505 pubmed
    ..PXE is caused by mutations in ABCC6, a gene encoding an ABC transporter predominantly expressed in liver and kidneys...
  21. Nitschke Y, Baujat G, Botschen U, Wittkampf T, du Moulin M, Stella J, et al. Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6. Am J Hum Genet. 2012;90:25-39 pubmed publisher
    ..GACI is associated with biallelic mutations in ENPP1 in the majority of cases, whereas mutations in ABCC6 are known to cause PXE. However, the genetic basis in subsets of both disease phenotypes remains elusive...
  22. Ringpfeil F, Lebwohl M, Christiano A, Uitto J. Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter. Proc Natl Acad Sci U S A. 2000;97:6001-6 pubmed
    ..1, without evidence for locus heterogeneity. In this study, we report pathogenetic mutations in MRP6, a member of the ABC transporter gene family, in eight kindreds with PXE...
  23. Gheduzzi D, Guidetti R, Anzivino C, Tarugi P, Di Leo E, Quaglino D, et al. ABCC6 mutations in Italian families affected by pseudoxanthoma elasticum (PXE). Hum Mutat. 2004;24:438-9 pubmed
    ..cardiovascular clinical symptoms, caused by mutations in a gene (ABCC6) that encodes for MRP6 (Multidrug Resistance associated Protein 6), an ATP-binding cassette membrane transporter...
  24. Pfendner E, Vanakker O, Terry S, Vourthis S, McAndrew P, McClain M, et al. Mutation detection in the ABCC6 gene and genotype-phenotype analysis in a large international case series affected by pseudoxanthoma elasticum. J Med Genet. 2007;44:621-8 pubmed
    ..It is caused by mutations in the ABCC6 (ATP binding cassette family C member 6) gene, which encodes MRP6 (multidrug resistance-associated protein 6)...
  25. Schulz V, Hendig D, Henjakovic M, Szliska C, Kleesiek K, Gotting C. Mutational analysis of the ABCC6 gene and the proximal ABCC6 gene promoter in German patients with pseudoxanthoma elasticum (PXE). Hum Mutat. 2006;27:831 pubmed
    ..Recently, ABCC6 mutations were identified as causing PXE...
  26. Wang M, Zhao S, Zhu P, Nie C, Ma S, Wang N, et al. Purification, characterization and immunomodulatory activity of water extractable polysaccharides from the swollen culms of Zizania latifolia. Int J Biol Macromol. 2017;: pubmed publisher
    ..1%, respectively. ZLPs-W3 with triple helix conformation mainly consisted of Man, Rha, GalA, Glc, Gal and Ara in the molar ratio of 10.23:14.14:37.44:17.14:16.54:4.51...
  27. Beck K, Hayashi K, Dang K, Hayashi M, Boyd C. Analysis of ABCC6 (MRP6) in normal human tissues. Histochem Cell Biol. 2005;123:517-28 pubmed
    To determine the tissue distribution of the ABC transporter ABCC6 in normal human tissues, we analyzed tissue arrays for the presence of ABCC6 mRNA by in situ hybridization and ABCC6 protein by immunohistochemistry using the polyclonal ..
  28. He W, Hu X, Jiang W, Liu R, Zhang D, Zhang J, et al. Rational Design of a New Self-Codelivery System from Redox-Sensitive Camptothecin-Cytarabine Conjugate Assembly for Effectively Synergistic Anticancer Therapy. Adv Healthc Mater. 2017;: pubmed publisher
    Herein, two careful selected anticancer drugs camptothecin (CPT) and cytarabine (Ara-C) with different biological action mechanisms and different water solubility are conjugated together through a glutathione (GSH) cleavable disulfide ..
  29. Wesener D, Levengood M, Kiessling L. Comparing Galactan Biosynthesis in Mycobacterium tuberculosis and Corynebacterium diphtheriae. J Biol Chem. 2017;292:2944-2955 pubmed publisher
    ..The mAG is composed of lipid mycolic acids, and arabinofuranose (Araf) and galactofuranose (Galf) carbohydrate residues...
  30. Jiang Q, Matsuzaki Y, Li K, Uitto J. Transcriptional regulation and characterization of the promoter region of the human ABCC6 gene. J Invest Dermatol. 2006;126:325-35 pubmed
    b>ABCC6, a member of the adenosine 5'-triphosphate-binding cassette family of genes, encodes multidrug resistance-associated protein 6, a putative transmembrane transporter expressed primarily in the liver and to a significantly lower ..
  31. van Soest S, Swart J, Tijmes N, Sandkuijl L, Rommers J, Bergen A. A locus for autosomal recessive pseudoxanthoma elasticum, with penetrance of vascular symptoms in carriers, maps to chromosome 16p13.1. Genome Res. 1997;7:830-4 pubmed
    Pseudoxanthoma elasticum (PXE) is a heritable systemic disorder characterized by calcification of the elastic fibers of the connective tissue...
  32. Norberg B, Kleppe L, Andersson E, Thorsen A, Rosenlund G, Hamre K. Effects of dietary arachidonic acid on the reproductive physiology of female Atlantic cod (Gadus morhua L.). Gen Comp Endocrinol. 2017;250:21-35 pubmed publisher
    The present study was designed to investigate potential effects of arachidonic acid (ARA) on the reproductive physiology of female Atlantic cod (Gadus morhua L.)...
  33. Zhou J, Lu X, Tan T, Chng W. XIAP inhibition sensitizes acute myeloid leukemia cells response to TRAIL and chemotherapy through potentiated induction of pro-apoptotic machinery. Mol Oncol. 2017;: pubmed publisher
    ..Combination of RO-BIR2 with Ara-C had similar effect as the TRAIL combination...
  34. Varatharajan S, Abraham A, Karathedath S, Ganesan S, Lakshmi K, Arthur N, et al. ATP-binding casette transporter expression in acute myeloid leukemia: association with in vitro cytotoxicity and prognostic markers. Pharmacogenomics. 2017;18:235-244 pubmed publisher
    ..There is limited data on the role of ABC transporter expression on in vitro sensitivity to cytarabine (Ara-C) and daunorubicin (Dnr) in primary AML cells.
  35. Cao H, Miao C, Yan L, Tang P, Zhang L, Sun L. Polymorphisms at microRNA binding sites of Ara-C and anthracyclines-metabolic pathway genes are associated with outcome of acute myeloid leukemia patients. J Transl Med. 2017;15:235 pubmed publisher
    ..This study investigated the association between poly-miRTS of Ara-C/anthracycline metabolic pathways genes and the outcome of acute myeloid leukemia (AML) in Chinese patients after ..
  36. Nitschke Y, Rutsch F. Genetics in arterial calcification: lessons learned from rare diseases. Trends Cardiovasc Med. 2012;22:145-9 pubmed publisher
    ..on the similarities of GACI, PXE, CALJA, and IBGC, it can be speculated that the underlying disease genes-ENPP1, ABCC6, NT5E, and SLC20A2, respectively-drive a cohesive molecular pathophysiology system modulated by ATP metabolism, ..
  37. Gorgels T, Teeling P, Meeldijk J, Nillesen S, van der Wal A, van Kuppevelt T, et al. Abcc6 deficiency in the mouse leads to calcification of collagen fibers in Bruch's membrane. Exp Eye Res. 2012;104:59-64 pubmed publisher
    ..The disease is caused by mutations in ABCC6. To learn more about PXE eye pathology, we analyzed Bruch's membrane (BM) of the eye of an Abcc6 knockout mouse...
  38. Ratajewski M, de Boussac H, Sachrajda I, Bacquet C, Kovacs T, Varadi A, et al. ABCC6 expression is regulated by CCAAT/enhancer-binding protein activating a primate-specific sequence located in the first intron of the gene. J Invest Dermatol. 2012;132:2709-17 pubmed publisher
    ..The disorder is due to loss-of-function mutations of the ABCC6 gene, but the pathophysiology of the disease is still not understood...
  39. Plomp A, Bergen A, Florijn R, Terry S, Toonstra J, van Dijk M, et al. Pseudoxanthoma elasticum: Wide phenotypic variation in homozygotes and no signs in heterozygotes for the c.3775delT mutation in ABCC6. Genet Med. 2009;11:852-8 pubmed publisher
    ..recessive disorder of elastic tissue in the skin, eyes, and cardiovascular system, caused by mutations in the ABCC6 gene...
  40. Sato N, Nakayama T, Mizutani Y, Yuzawa M. Novel mutations of ABCC6 gene in Japanese patients with Angioid streaks. Biochem Biophys Res Commun. 2009;380:548-53 pubmed publisher
    ..The ATP-binding cassette, sub-family C (CFTR/MRP), member 6 (ABCC6) is reported to be the causal gene for PXE, although there have been no reports on whether the ABCC6 gene is the ..
  41. Hannivoort R, Dunning S, Vander Borght S, Schroyen B, Woudenberg J, Oakley F, et al. Multidrug resistance-associated proteins are crucial for the viability of activated rat hepatic stellate cells. Hepatology. 2008;48:624-34 pubmed publisher
    ..of Mrp3, Mrp4, Mdr1a, and Mdr1b but not the hepatocyte-specific transporters bile salt export pump, Mrp2, and Mrp6. Mrp1 protein staining correlated with desmin staining in livers from CCl(4)-treated rats...