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. 2016 Jan 18:17:9.
doi: 10.1186/s13059-016-0869-4.

The intolerance to functional genetic variation of protein domains predicts the localization of pathogenic mutations within genes

Ayal B Gussow  1   2 , Slavé Petrovski  3   4 , Quanli Wang  5 , Andrew S Allen  6 , David B Goldstein  7
Affiliations

The intolerance to functional genetic variation of protein domains predicts the localization of pathogenic mutations within genes

Ayal B Gussow et al. Genome Biol. .

Abstract

Ranking human genes based on their tolerance to functional genetic variation can greatly facilitate patient genome interpretation. It is well established, however, that different parts of proteins can have different functions, suggesting that it will ultimately be more informative to focus attention on functionally distinct portions of genes. Here we evaluate the intolerance of genic sub-regions using two biological sub-region classifications. We show that the intolerance scores of these sub-regions significantly correlate with reported pathogenic mutations. This observation extends the utility of intolerance scores to indicating where pathogenic mutations are mostly likely to fall within genes.

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Figures

Fig. 1
Fig. 1
Distribution of reported pathogenic variants in ATP1A3. This figure shows the distribution of reported variants in ATP1A3. Each CDD conserved domain type is annotated in a different color. The Y axis represents the domain subRVIS scores. Each reported variant is marked with a blue circle
Fig. 2
Fig. 2
Distribution of reported pathogenic variants in MAPT. This figure shows the distribution of reported variants in MAPT. Each CDD conserved domain type is annotated in a different color. The Y axis represents the domain subRVIS scores. Each reported variant is marked with a blue circle
See this image and copyright information in PMC

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