%A Zanzoni,Andreas %A Chapple,Charles %A Brun,Christine %D 2015 %J Frontiers in Physiology %C %F %G English %K Human Disease,protein-protein interactions,Multifunctional proteins,Disease comorbidity,Moonlighting Proteins %Q %R 10.3389/fphys.2015.00171 %W %L %M %P %7 %8 2015-June-23 %9 Original Research %+ Dr Christine Brun,Inserm,TAGC UMR1090,Parc Scientifique et Technologique de Luminy,Case 928,Marseille,13288,France,christine-g.brun@inserm.fr %+ Dr Christine Brun,Aix-Marseille University,Parc Scientifique et Technologique de Luminy,Case 928,Marseille,13288,France,christine-g.brun@inserm.fr %# %! Moonlighting and disease %* %< %T Relationships between predicted moonlighting proteins, human diseases, and comorbidities from a network perspective %U https://www.frontiersin.org/articles/10.3389/fphys.2015.00171 %V 6 %0 JOURNAL ARTICLE %@ 1664-042X %X Moonlighting proteins are a subset of multifunctional proteins characterized by their multiple, independent, and unrelated biological functions. We recently set up a large-scale identification of moonlighting proteins using a protein-protein interaction (PPI) network approach. We established that 3% of the current human interactome is composed of predicted moonlighting proteins. We found that disease-related genes are over-represented among those candidates. Here, by comparing moonlighting candidates to non-candidates as groups, we further show that (i) they are significantly involved in more than one disease, (ii) they contribute to complex rather than monogenic diseases, (iii) the diseases in which they are involved are phenotypically different according to their annotations, finally, (iv) they are enriched for diseases pairs showing statistically significant comorbidity patterns based on Medicare records. Altogether, our results suggest that some observed comorbidities between phenotypically different diseases could be due to a shared protein involved in unrelated biological processes.