Genomic cloning, structure, expression pattern, and chromosomal location of the human SIX3 gene

Genomics. 1999 Jan 1;55(1):100-5. doi: 10.1006/geno.1998.5611.


The Drosophila gene sine oculis (so) is a nuclear homeoprotein that is required for eye development. Homologous genes to so, denoted SIX genes, have been found in vertebrates. Among the SIX genes, SIX3 is considered to be the functional homologue of so. To provide insight into the potential implications of SIX3 in human ocular malformations, we have cloned and characterized the human SIX3 gene. In human eye, SIX3 produces a 3-kb transcript that codes for a 332-amino-acid polypeptide that is virtually identical to its mouse and chick homologues. Expression of SIX3 was detected in human embryos as early as 5-7 weeks of gestation and found to be maintained in the eye throughout the entire period of fetal development. At 20 weeks of gestation, expression of SIX3 in the human retina was detected in the ganglion cells and in cells of the inner nuclear layer. The human SIX3 gene spans 4.4 kb of genomic DNA and is split in two exons separated by a 1659-bp intron. SIX3 was mapped to human chromosome 2p16-p21, between the genetic markers D2S119 and D2S288. Interestingly, the map position of human SIX3 overlaps the locations of two dominant disorders with ocular phenotypes that have been assigned to this chromosomal region, holoprosencephaly type 2 and Malattia Leventinese.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 2*
  • Cloning, Molecular
  • DNA
  • Eye / embryology
  • Eye / metabolism
  • Eye Proteins / genetics*
  • Gene Expression
  • Homeodomain Proteins / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Sequence Homology, Amino Acid


  • Eye Proteins
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Sine oculis homeobox homolog 3 protein
  • DNA

Associated data

  • GENBANK/AF092047
  • GENBANK/H84264