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A gene encoding a novel transmembrane protein was identified by DNA sequence analysis within the insulin-dependent diabetes mellitus (IDDM) locus IDDM4 on chromosome 11q13. Based on its chromosomal position, this gene is a candidate for conferring susceptibility to diabetes. The gene, termed low-density lipoprotein receptor related protein 5 (LRP5), encodes a protein of 1615 amino acids that contains conserved modules which are characteristic of the low-density lipoprotein (LDL) receptor family. These modules include a putative signal peptide for protein export, four epidermal growth factor (EGF) repeats with associated spacer domains, three LDL-receptor (LDLR) repeats, a single transmembrane spanning domain, and a cytoplasmic domain. The encoded protein has a unique organization of EGF and LDLR repeats; therefore, LRP5 likely represents a new category of the LDLR family. Both human and mouse LRP5 cDNAs have been isolated and the encoded mature proteins are 95% identical, indicating a high degree of evolutionary conservation.

Original publication




Journal article



Publication Date





103 - 111


Amino Acid Sequence, Animals, Chromosomes, Human, Pair 11, Cloning, Molecular, Cosmids, DNA, DNA, Bacterial, DNA, Complementary, Diabetes Mellitus, Type 1, Gene Expression, Genetic Predisposition to Disease, Genomic Library, Humans, LDL-Receptor Related Proteins, Low Density Lipoprotein Receptor-Related Protein-5, Membrane Proteins, Mice, Microsatellite Repeats, Molecular Sequence Data, Receptors, LDL, Sequence Alignment, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Tissue Distribution