The calcium-sensing receptor (CaSR) belongs to family C of G-protein coupled receptors (GPCRs) that bind glutamate, GABA, taste molecules and pheromones. Loss-of-function mutations of the CASR gene located on chromosome 3q2124, cause familial benign hypocalciuric hypercalcaemia type 1 (FBHH1). The genes causing FBHH2 and FBHH3, whose chromosomal locations are on 19p and 19q13.3, respectively, remain unknown. FBHH3, sometimes called the Oklahoma variant (FBHHOk), maps to a <10 centimorgan interval on 19q13.3 that contains >140 genes, which in the syntenic region on mouse chromosome 7 contains 4 Casr-related sequences referred to as Casr-rs1, Casr-rs3, Casr-rs4 and Casr-rs5. The Casr-rss are GPCRs and encode pheromone receptors. Casr-rs1, which has 81% amino acid identity to mouse vomeronasal 2- receptor 6 (V2r6) and 40% identity to the human CaSR, seemed to be a likely candidate for FBHH3. However, a National Centre for Biotechnology Information (NCBI) database search revealed no human homologues of Casr-rs1 or any of the other Casr-rss, thereby precluding their mutational analysis for FBHH3. A comparative analysis of human chromosome 19q13 and the syntenic region of mouse chromosome 7 revealed a loss, from the human genome, of a 5.1 Mb region that contains 32 murine genes including the 4 Casr-rss. In mouse, this 5.1 Mb region lies within a 33.4 Mb segment, in which the centromeric 25.8 Mb and telomeric 2.5 Mb are otherwise evolutionary conserved between mouse and man; however, a comparative analysis of the mouse and human revealed that centromeric and telomeric segments have undergone complex inversions. These findings of multiple rearrangements of the FBHH3 candidate region between man and mouse are consistent with human chromosome 19 having the highest breakpoint density, and may also explain the loss of calcium-sensing receptor related sequences (casr-rss) from the FBHH3 candidate interval during chromosomal evolution.