Defects in SIX3 are the cause of holoprosencephaly type 2 (HPE2) [MIM:157170]. Holoprosencephaly (HPE) [MIM:236100] is the most common structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability.
Belongs to the SIX/Sine oculis homeobox family. Contains 1 homeobox DNA-binding domain.