WDR11, a WD protein that interacts with transcription factor EMX1, is mutated in idiopathic hypogonadotropic hypogonadism and Kallmann syndrome

Am J Hum Genet. 2010 Oct 8;87(4):465-79. doi: 10.1016/j.ajhg.2010.08.018.


By defining the chromosomal breakpoint of a balanced t(10;12) translocation from a subject with Kallmann syndrome and scanning genes in its vicinity in unrelated hypogonadal subjects, we have identified WDR11 as a gene involved in human puberty. We found six patients with a total of five different heterozygous WDR11 missense mutations, including three alterations (A435T, R448Q, and H690Q) in WD domains important for β propeller formation and protein-protein interaction. In addition, we discovered that WDR11 interacts with EMX1, a homeodomain transcription factor involved in the development of olfactory neurons, and that missense alterations reduce or abolish this interaction. Our findings suggest that impaired pubertal development in these patients results from a deficiency of productive WDR11 protein interaction.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Chromosomes, Human, Pair 10 / genetics*
  • Homeodomain Proteins / genetics*
  • Humans
  • Hypogonadism / genetics*
  • Immunoblotting
  • Immunohistochemistry
  • Immunoprecipitation
  • In Situ Hybridization
  • In Situ Hybridization, Fluorescence
  • Kallmann Syndrome / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Microarray Analysis
  • Mutation, Missense / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Puberty / genetics*
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics*
  • Translocation, Genetic / genetics*
  • Two-Hybrid System Techniques
  • Zebrafish


  • Homeodomain Proteins
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Transcription Factors
  • WDR11 protein, human
  • empty spiracles homeobox proteins