G143R mutation of human GJA3 gene is located at the cytoplasmic loop domain of Cx46 protein.

A) The membrane topological structure of Cx46 was generated by TOPO2. G143R mutation (indicated by solid black square) is located in the cytoplasmic loop domain. N, NH₂-terminus; C, COOH-terminus; E1, first extracellular loop domain; E2, second extracellular loop domain; CL, cytoplasmic loop domain. B) Glycine at position 143 of Cx46 protein is highly conserved in Cx46 across animal species. C) Amino acid residue Gly-143 is also conserved in different human connexins.