Two new genes from the human ATP-binding cassette transporter superfamily, ABCC11 and ABCC12, tandemly duplicated on chromosome 16q12 Jaana Tammur a,b , Catherine Prades c , Isabelle Arnould c , Andrey Rzhetsky d , Amy Hutchinson b , Masashi Adachi e , John D. Schuetz e , Kathryn J. Swoboda f,g,h , Louis J. Pta Âcek f,h,i , Marie Rosier c , Michael Dean j , Rando Allikmets b,k, * a Department of Biotechnology, Institute of Molecular and Cell Biology, Tartu University, Tartu, Estonia b Department of Ophthalmology, Columbia University, New York, NY, USA c Functional Genomics Department, Aventis Pharma, Paris, France d Columbia Genome Center, Columbia University, New York, NY, USA e Department of Pharmacological Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA f Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA g Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA h Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA i Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT, USA j Laboratory of Genomic Diversity, NCI-FCRDC, Frederick, MD, USA k Department of Pathology, Columbia University, New York, NY, USA Received 7 March 2001; received in revised form 18 May 2001; accepted 14 June 2001 Received by M. D'Urso Abstract Several years ago, we initiated a long-term project of cloning new human ATP-binding cassette (ABC) transporters and linking them to various disease phenotypes. As one of the results of this project, we present two new members of the human ABCC subfamily, ABCC11 and ABCC12. These two new human ABC transporters were fully characterized and mapped to the human chromosome 16q12. With the addition of these two genes, the complete human ABCC subfamily has 12 identi®ed members (ABCC1±12), nine from the multidrug resistance-like subgroup, two from the sulfonylurea receptor subgroup, and the CFTR gene. Phylogenetic analysis determined that ABCC11 and ABCC12 are derived by duplication, and are most closely related to the ABCC5 gene. Genetic variation in some ABCC subfamily members is associated with human inherited diseases, including cystic ®brosis (CFTR/ABCC7), Dubin±Johnson syndrome (ABCC2), pseudoxanthoma elasticum (ABCC6) and familial persistent hyperinsulinemic hypoglycemia of infancy (ABCC8). Since ABCC11 and ABCC12 were mapped to a region harboring gene(s) for paroxysmal kinesigenic choreoathetosis, the two genes represent positional candidates for this disorder. q 2001 Elsevier Science B.V. All rights reserved. Keywords: ATP-binding cassette transporters; Mapping; Paroxysmal kinesigenic choreoathetosis 1. Introduction The ATP-binding cassette (ABC) transporter superfamily is one of the largest gene families and encodes a function- ally diverse group of membrane proteins involved in energy-dependent transport of a wide variety of substrates across membranes (Dean and Allikmets, 1995). Phyloge- netic analysis further divides human ABC transporters into seven subfamilies: ABCA (ABC1 subfamily), ABCB (MDR/TAP subfamily), ABCC (CFTR/MRP subfamily), ABCD (ALD subfamily), ABCE (OABP subfamily), ABCF (GCN20 subfamily), and ABCG (white subfamily) Gene 273 (2001) 89±96 0378-1119/01/$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S0378-1119(01)00572-8 www.elsevier.com/locate/gene Abbreviations: ABC, ATP-binding cassette; BAC, bacterial arti®cial chromosome; bp, base pair(s); CEM, a human T-lymphoid cell line; CEM-r1, a PMEA-resistant variant of CEMss; CEMss, a human T- lymphoid cell line sensitive to PMEA; EST, expressed sequence tag; GSH, glutathione; ICCA, infantile convulsions with paroxysmal chor- eoathetosis; MRP, multidrug resistance protein; MTX, methotrexate; PCR, polymerase chain reaction; PKC, paroxysmal kinesigenic choreoathe- tosis; PMEA, 9-(2-phosphonylmethoxyethyl) adenine; 3TC, 2 0 ,3 0 -dideoxy- 3 0 -thiacytidine; UTR, untranslated region * Corresponding author. Department of Ophthalmology, Columbia University, Eye Research Addition, Room 715, 630 West 168th Street, New York, NY 10032, USA. Tel.: 11-212-305-8989; fax: 11-212-305- 7014. E-mail address: rla22@columbia.edu (R. Allikmets).