prolyl endopeptidase belonging to the prolyl oligopeptidase family; and (3) CAMKMT encoding a calmodulin-lysine N-methyltransferase. This region is well-known for two contiguous gene-deletion syndromes, the hypotonia-cystinuria syndrome and the more severe 2p21 deletion syndrome (29). Deletion of SLC3A1 results in the autosomal-recessive form of cystinuria (30), while PREPL deletion causes hypotonia at birth, failure to thrive and growth hormone deficiency (31). The evolutionarily conserved class I protein methyltransferase encoded by CAMKMT acts in the formation of trimethyllysine in calmodulin which is involved in calcium-dependent signaling (32). Interestingly, GWAS of schizophrenia and bipolar disorder have highlighted other genes encoding proteins involved in calcium-dependent signaling (33). Although the most significant SNP, rs1067327, is located in an intron of CAMKMT , in silico analyses (Supplement) suggest rs698775 is the most likely functional candidate with a cis regulatory effect possibly specific to PREPL.
