Prediction of disease-related mutations affecting protein localizationReport as inadecuate

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BMC Genomics

, 10:122

First Online: 23 March 2009Received: 29 September 2008Accepted: 23 March 2009


BackgroundEukaryotic cells contain numerous compartments, which have different protein constituents. Proteins are typically directed to compartments by short peptide sequences that act as targeting signals. Translocation to the proper compartment allows a protein to form the necessary interactions with its partners and take part in biological networks such as signalling and metabolic pathways. If a protein is not transported to the correct intracellular compartment either the reaction performed or information carried by the protein does not reach the proper site, causing either inactivation of central reactions or misregulation of signalling cascades, or the mislocalized active protein has harmful effects by acting in the wrong place.

ResultsNumerous methods have been developed to predict protein subcellular localization with quite high accuracy. We applied bioinformatics methods to investigate the effects of known disease-related mutations on protein targeting and localization by analyzing over 22,000 missense mutations in more than 1,500 proteins with two complementary prediction approaches. Several hundred putative localization affecting mutations were identified and investigated statistically.

ConclusionAlthough alterations to localization signals are rare, these effects should be taken into account when analyzing the consequences of disease-related mutations.



ERER lumen

fnfalse negative. false positive

GGolgi apparatus

gPMplasma membrane, GPI anchor

GtmGolgi, transmembrane

HGMDHuman Gene Mutation Database

HPRDHuman Protein Reference Database



Mmamitochondrial matrix

mPMplasma membrane, myristoylated

Mpsmitochondrial periplasmic space

Mtmmitochondrial membrane, transmembrane


OMIMOnline Mendelian Inheritance in Man


PMplasma membrane

RCreliability coefficient


SPScandinavian Protocol

tntrue negative

tptrue positive.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-10-122 contains supplementary material, which is available to authorized users.

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Author: Kirsti Laurila - Mauno Vihinen


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