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Annika Kreuchwig, Gunnar Kleinau, Franziska Kreuchwig, Catherine L. Worth, Gerd Krause (Leibniz-Institut für Molekulare Pharmakologie, Robert-Rössle-Str. 10, 13125 Berlin, Germany)There are many attempts to collect functional data of genetic variations in proteins, but tools to analyze the molecular effects of biologically relevant residues to explain gain or loss of function mutations are as yet poorly provided. Our Sequence-Structure-Function-Analysis toolbox offers search and visualization tools for studying structural and functional properties of individual amino acid residues either by 2D features such as interactive and user-defined snake-plots or by 3D structures. 3D structures are used to project the functional data in their spatial neighborhood which helps to detect crucial residues for intra- or intermolecular interactions thus providing deeper insights into molecular activation mechanisms. The simulation of molecular changes by morphing supports the interpretation of functional findings. The functional data are converted into relational percentage values; thereby the system allows the comparison of data from different proteins and various experimental approaches. Our toolbox has been incorporated into a website for Glycoprotein Hormone Receptors (http://www.ssfa-gphr.de), but the framework may also be adaptable to other macromolecules.