The novel gene encoding a putative transmembrane protein is mutated in gnathodiaphyseal dysplasia (GDD)

Am J Hum Genet. 2004 Jun;74(6):1255-61. doi: 10.1086/421527. Epub 2004 Apr 29.


Gnathodiaphyseal dysplasia (GDD) is a rare skeletal syndrome characterized by bone fragility, sclerosis of tubular bones, and cemento-osseous lesions of the jawbone. By linkage analysis of a large Japanese family with GDD, we previously mapped the GDD locus to chromosome 11p14.3-15.1. In the critical region determined by recombination mapping, we identified a novel gene (GDD1) that encodes a 913-amino-acid protein containing eight putative transmembrane-spanning domains. Two missense mutations (C356R and C356G) of GDD1 were identified in the two families with GDD (the original Japanese family and a new African American family), and both missense mutations occur at the cysteine residue at amino acid 356, which is evolutionarily conserved among human, mouse, zebrafish, fruit fly, and mosquito. Cellular localization to the endoplasmic reticulum suggests a role for GDD1 in the regulation of intracellular calcium homeostasis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Calcium / metabolism
  • Camurati-Engelmann Syndrome / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 11*
  • Cloning, Molecular
  • Cricetinae
  • Endoplasmic Reticulum / metabolism
  • Female
  • Genes, Dominant
  • Genetic Linkage
  • Humans
  • Jaw Abnormalities / genetics*
  • Lod Score
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Molecular Sequence Data
  • Mutation, Missense / genetics*
  • Pedigree
  • Sequence Homology, Amino Acid
  • Tissue Distribution
  • Transfection


  • Membrane Proteins
  • Calcium

Associated data

  • GENBANK/AB125267
  • GENBANK/AL833271
  • RefSeq/NM_004211
  • RefSeq/NM_005256
  • RefSeq/NM_006157
  • RefSeq/NM_006410
  • RefSeq/NM_020346
  • RefSeq/NM_022725
  • RefSeq/NM_182964
  • RefSeq/NP_648535
  • RefSeq/XM_058460
  • RefSeq/XP_311470