Despite this success only two association signals were low frequency variants, H177Y MAF 0.8% at G6PC2/ABCB11 and E594V MAF 0.1% at URB2, (Table 1), and the data supported PCSK1, RREB1 and ZHX3 as likely effector transcripts at the associated loci, with RREB1 also replicated in a type 2 diabetes study (7), confirming it as the probable effector gene for T2D at the SSR1 locus. This evidence concerns the gene ZHX3 and type 2 diabetes mellitus.