Imperial College London


Faculty of Natural SciencesDepartment of Life Sciences

Director Centre for Bioinformatics



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BibTex format

author = {Ittisoponpisan, S and Sternberg, MJE and Alhuzimi, E and David, A},
doi = {10.1002/humu.23155},
journal = {Human Mutation},
pages = {289--296},
title = {Landscape of pleiotropic proteins causing human disease: structural and system biology insights},
url = {},
volume = {38},
year = {2017}

RIS format (EndNote, RefMan)

AB - Pleiotropyis the phenomenon by which the same gene can result in multiple phenotypes. Pleiotropic proteins are emerging as important contributors to rare and common disorders. Nevertheless, little is known on the mechanisms underlying pleiotropy and the characteristic of pleiotropic proteins.We analysed disease-causing proteins reported in UniProt and observed that 12% are pleiotropic (variants in the same protein cause more than one disease). Pleiotropic proteins were enriched indeleterious and rare variants, but not in common variants. Pleiotropic proteins were more likely to be involved in the pathogenesis of neoplasms, neurological and circulatory diseases, and congenital malformations, whereas non-pleiotropicproteinsin endocrine and metabolic disorders. Pleiotropic proteins were more essential and hada higher number of interacting partners compared to non-pleiotropic proteins. Significantly more pleiotropic than non-pleiotropic proteins contained at least one intrinsically long disordered region (p<0.001). Deleterious variants occurring in structurally disordered regions were more commonly found in pleiotropic, rather than non-pleiotropic proteins. 14In conclusion, pleiotropic proteins are an important contributor to human disease. They represent a biologically different class of proteins compared to non-pleiotropic proteins anda better understanding of their characteristicsand genetic variants, cangreatly aid in the interpretation of genetic studies and drug design.
AU - Ittisoponpisan,S
AU - Sternberg,MJE
AU - Alhuzimi,E
AU - David,A
DO - 10.1002/humu.23155
EP - 296
PY - 2017///
SN - 1098-1004
SP - 289
TI - Landscape of pleiotropic proteins causing human disease: structural and system biology insights
T2 - Human Mutation
UR -
UR -
VL - 38
ER -