Characterization of the HSD17B4 gene: D-specific multifunctional protein 2/17 beta-hydroxysteroid dehydrogenase IV

The HSD17B4 gene codes for a 80 kDa multifunctional enzyme containing three distinct functional domains and is localized in peroxisomes. The N-termina l part exhibits 3-hydroxyacyl-CoA dehydrogenase and 17 beta-hydroxysteroid dehydrogenase activity whereas the central part shows enoyl-CoA hydratase a ctivity. The carboxy-terminal part of the protein has sterol-carrier-protei n activity. The protein is widely expressed, however in several tissues lik e brain, uterus and lung its expression is limited to specific cells like P urkinje cells or luminal epithelium. The HSD17B4 gene consist of 24 exons a nd 23 introns with classical intron-exon junctions spanning more than 100 k bp. The importance of the HSD17B4 protein is stressed by the identification of patients with severe clinical abnormalities due to mutations in the HSD 17B4 gene. We have now checked the consequences of one frequent mutation, G 16 S, which results in inactivation of the enzyme due to loss of interactio n with NAD+. (C) 1999 Elsevier Science Ltd. All rights reserved.