Fig. 2

A Schematic representation of ZNRF3 protein indicating the known functional domains. The sequence alignment indicating the position and evolutionary conservation of the mutated isoleucine 338 residue, immediately adjacent to the RING finger domain. Previously published variants linked to 46,XY DSD are shown and located within the intracellular domain. B Schematic representation of HHAT protein indicating the position of the mutated p.R312 residue. Other published variants associated with this syndromic form of 46,XY DSD are indicated. C Representation of the SOX8 protein showing the position of the mutated p.T226 residue located in the evolutionary conserved TA1 domain. The only other SOX8 variant known to be associated with 46,XY DSD is the p.E156D mutation located within the HMG-box. Right, the mutated threonine residue is conserved in the SOXE group of proteins. DIM, DNA-dependent dimerization domain; HMG, high mobility group; MBOAT, Membrane Bound O-Acyltransferase domain; TA, transactivation domain; TM, transmembrane domain; SP, signal peptide