A cDNA that encodes a putative Ca(2+)-sensing receptor (HuKCaSR) was cloned from human kidney with the use of the polymerase chain reaction. The predicted HuKCaSR protein consists of 1078 amino acids and shares 93.1 and 93.8% overall identity with the bovine parathyroid Ca(2+)-sensing receptor (BoPCaR1) and rat kidney Ca(2+)-sensing receptor (RaKCaR), respectively, with least similarity in the carboxyl-terminal regions. The HuKCaSR gene was mapped by fluorescence in situ hybridization to chromosome 3q21, at which region the gene responsible for familial hypocalciuric hypercalcemia has previously been localized by genetic linkage analyses. RNA blot analysis revealed HuKCaSR mRNA in human kidney, but not in brain, lung, liver, heart, skeletal muscle, or placenta.