Na/Cl cotransporter 2 is not fish-specific and is widely found in amphibians, non-avian reptiles, and select mammals.

Solute carrier 12 (Slc12) is a family of electroneutral cation-coupled chloride (Cl) cotransporters. Na/K/2Cl (Nkcc) and Na/Cl cotransporters (Ncc) belong to the Nkcc/Ncc subfamily. Human and mouse possess one gene for the Na/Cl cotransporter ( gene: ), whereas teleost fishes possess multiple genes, () and (), in addition to their species-specific paralogs. Amphibians and squamates have two genes: () and . However, the evolutionary relationship between and remains unresolved, and the presence of () in mammals has not been clarified. Synteny and phylogenetic analyses of vertebrate genome databases showed that is the ortholog of , and is present in most ray-finned fishes, coelacanths, amphibians, reptiles, and a few mammals (e.g., platypus and horse) but pseudogenized or deleted in birds, most mammals, and some ray-finned fishes (pufferfishes). This shows that is widely present among bony vertebrates and pseudogenized or deleted independently in multiple lineages. Notably, as compared with some fish that show varied tissue expression profile, spotted gar, African clawed frog, red-eared slider turtle, and horse express in the ovaries or premature gonads. In horse tissues, an unexpectedly large number of splicing variants for Slc12a10 have been cloned, many of which encode truncated forms of Slc12a10, suggesting that the functional constraints of horse are weakened, which may be in the process of becoming a pseudogene. Our results elaborate on the evolution of Nkcc/Ncc subfamily of Slc12 in vertebrates. is not a fish-specific gene and is present in a few mammals (e.g., platypus and horse), non-avian reptiles, amphibians, but was pseudogenized or deleted in most mammals (e.g., human, mouse, cat, cow, and rhinoceros), birds, and some ray-finned fishes (pufferfishes).