Technological advances hold the promise of rapidly catalyzing the discovery of pathogenic variants for genetic disease. However, this possibility is tempered by limitations in interpreting the functional consequences of genetic variation at candidate …
Successful establishment and persistence of adenovirus (Ad) infections are facilitated by immunosubversive functions encoded in the early transcription unit 3 (E3). The E3/19K protein has a dual role, preventing cell surface transport of MHC class …
The melanocortin 4 receptor (MC4R) is a G-protein-coupled receptor (GPCR) and a key molecule in the regulation of energy homeostasis. At least 159 substitutions in the coding region of human MC4R (hMC4R) have been described experimentally; over 80 of …
BACKGROUND: Mutations resulting in the disruption of protein function are the underlying causes of many genetic diseases. Some mutations affect the number of expressed proteins while others alter the activity on a per-molecule basis. Single amino …
The rapidly increasing quantity of protein sequence data continues to widen the gap between available sequences and annotations. Comparative modeling suggests some aspects of the 3D structures of approximately half of all known proteins; homology- …
Functionally significant heterozygous mutations in the Melanocortin-4 receptor (MC4R) have been implicated in 2.5% of early onset obesity cases in European cohorts. The role of mutations in this gene in severely obese adults, particularly in smaller …
MOTIVATION: Mutating residues into alanine (alanine scanning) is one of the fastest experimental means of probing hypotheses about protein function. Alanine scans can reveal functional hot spots, i.e. residues that alter function upon mutation. In …
Many non-synonymous single nucleotide polymorphisms (nsSNPs) in humans are suspected to impact protein function. Here, we present a publicly available server implementation of the method SNAP (screening for non-acceptable polymorphisms) that predicts …
In 404 Lep(ob/ob) F2 progeny of a C57BL/6J (B6) x DBA/2J (DBA) intercross, we mapped a DBA-related quantitative trait locus (QTL) to distal Chr1 at 169.6 Mb, centered about D1Mit110, for diabetes-related phenotypes that included blood glucose, HbA1c, …
Many genetic variations are single nucleotide polymorphisms (SNPs). Non-synonymous SNPs are 'neutral' if the resulting point-mutated protein is not functionally discernible from the wild type and 'non-neutral' otherwise. The ability to identify …