A novel member of a zinc transporter family is defective in acrodermatitis enteropathica.
The rare inherited condition acrodermatitis enteropathica (AE) results from a defect in the absorption of dietary zinc. Recently, we used homozygosity mapping in consanguineous Middle Eastern kindreds to localize the AE gene to an approximately 3.5-cM region on 8q24. In this article, we identify a gene, SLC39A4, located in the candidate region and, in patients with AE, document mutations that likely lead to the disease. The gene encodes a histidine-rich protein, which we refer to as "hZIP4," which is a member of a large family of transmembrane proteins, some of which are known to serve as zinc-uptake proteins. We show that Slc39A4 is abundantly expressed in mouse enterocytes and that the protein resides in the apical membrane of these cells. These findings suggest that the hZIP4 transporter is responsible for intestinal absorption of zinc.
Wang
Kun
K
Howard Hughes Medical Institute and Department of Medicine, University of California, San Francisco, 94143, USA.
Zhou
Bing
B
Kuo
Yien-Ming
YM
Zemansky
Jason
J
Gitschier
Jane
J
D000169:Acrodermatitis / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D020895:Enterocytes / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D015032:Zinc / Q000378:metabolism*
D002352:Carrier Proteins; D008565:Membrane Proteins; D015032:Zinc