Figure 12.The V2-R is a 7 transmembrane spanning domain G-protein coupled receptor. Codon 137 of theV2-Rgene encodes an amino acid located at the cytoplasmic boundary of the third transmembrane spanning domain. Mutations of theV2-Rgene affecting codon 137 cause both NDI and NSIAD. Codon 137 of the wild type V2-R encodes the amino acid Arginine (R). In X-linked NDI, the V2-R gene is mutated such that codon 137 encodes the amino acid Histidine (H). This renders the receptor inactive and unable to couple ligand binding with G-protein activation. Mutations in theV2-Rgene found in NSIAD also affect codon 137; changing the amino acid of the receptor to either Cysteine (C) or Leucine (L).