Figure 3. Schematic showing gene structure and protein domains of GJA3. A: Exon organization and mutation profile of GJA3. The entire coding region (435 amino-acids) is located in exon-2. Based on hydrophobicity analysis [34], GJA3 has nine structural domains including: a cytoplasmic N-terminus (NT), 4 transmembrane domains (TM-1 – TM-4); 2 extracellular loops (EC1, EC2), a cytoplasmic loop (CL), and a cytoplasmic C-terminus (CT). The relative locations, with respect to the translation start codon, of the p.V44M mutation and 19 other mutations associated with autosomal dominant cataract in humans are indicated. The rat p.E42K mutation associated with autosomal recessive cataract is also indicated. B: Amino-acid sequence alignment of the first extracellular (EC-1) domain (amino-acids 42–71) from human GJA3 and homologs from other species. Dots denote identical amino-acids. Cysteine residues involved in hemi-channel docking are underlined. Missense substitutions are shown in red.