UniProt genomic mapping for deciphering functional effects of missense variants

The integration of protein function knowledge in the UniProt Knowledgebase (UniProtKB) with genomic data provides unique opportunities for biomedical research by helping scientists to rapidly comprehend complex processes in biology. UniProtKB provides expert curation of functionally characterized variants reported in the literature, many of them associated with disease. Understanding the association of genetic variation with its functional consequences in proteins is essential for the interpretation of large-scale genomics data. UniProtKB protein sequences and sequence feature annotations such as active sites, modified sites, binding domains and amino acid variation have been mapped to the current build of the human genome (GRCh38). We have also created public track hubs for the Ensembl and UCSC browsers. We examine some specific biological examples in disease-related genes and proteins, illustrating the utility of combining protein and genome annotations for the functional interpretation of variants. We also present a larger comparison of UniProtKB variant and feature curation data that collocates with clinically observed SNP data from ClinVar, illustrating how protein and gene disease annotations currently compare and discuss some additional uses that might follow with combined annotation. The combination of gene and protein annotation can assist medical geneticists with the functional interpretation of variation. The genomic track hubs are downloadable from the UniProt FTP site (http://www.uniprot.org/downloads) and directly discoverable as public track hubs at the USCS and Ensembl genome browsers.

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