Despite these parentally pre-programmed epigenetic behaviors, human M6P/IGF2R transcription appears to be equivalent between both parentally-inherited alleles. Thus, human M6P/IGF2R alleles are encoded with information about parental origin, but this information is evidently uncoupled from transcriptional ramifications. This uncoupling is particularly intriguing in light of mouse genetic manipulations which causally link an imprinted M6p/igf2r DMR to imprinted transcription. Thus, the human M6P/IGF2R provides a rare example of uncoupling of stable gene imprinting --evidenced by somatically heritable parent-specific DNA methylation-- from stable imprinted transcription. Interestingly, the marsupial M6P/IGF2R homologue manifests parentally imprinted maternal transcription in the absence of imprinted differential methylation.

M6P/IGF2R, thus, is remarkably divergent across animal species with respect to both biochemical and epigenetic properties. Within the imprinted family of genes, M6P/IGF2R manifests a distinctive uncoupling of imprinted methylation from imprinted transcription, which frustrates efforts to establish the precise role of DNA methylation in the imprinting process. M6P/IGF2R is somewhat of a devil's advocate and a reminder that genes don't always read the journals.