NOBOX homeobox mutation causes premature ovarian failure

Am J Hum Genet. 2007 Sep;81(3):576-81. doi: 10.1086/519496. Epub 2007 Jul 10.


NOBOX (newborn ovary homeobox gene) is an oocyte-specific homeobox gene that plays a critical role in early folliculogenesis and represents a candidate gene for nonsyndromic ovarian failure. We investigated whether mutations in the NOBOX gene cause premature ovarian failure (POF). We sequenced the NOBOX gene in 96 white women with POF and discovered seven known single-nucleotide polymorphisms and four novel variations, two of which, p.Arg355His and p.Arg360Gln, cause missense mutations in the homeobox domain. Electrophoretic mobility shift assay (EMSA) confirmed that the missense mutation, p.Arg355His, disrupted NOBOX homeodomain binding to NOBOX DNA-binding element (NBE) and had a dominant negative effect on the binding of wild-type NOBOX to DNA. Our findings demonstrate that NOBOX mutations can cause POF.

Publication types

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

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Amino Acid Substitution / genetics
  • Arginine / chemistry
  • Arginine / genetics
  • Female
  • Homeodomain Proteins / genetics*
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Primary Ovarian Insufficiency / genetics*
  • Transcription Factors / genetics*


  • Homeodomain Proteins
  • NOBOX protein, human
  • Transcription Factors
  • Arginine

Associated data

  • RefSeq/NM_001080413
  • RefSeq/XP_001134420