Fig. 2: Modeling variant effect on CSMD1 protein. | Cell Death & Disease

Fig. 2: Modeling variant effect on CSMD1 protein.

From: Biallelic variants in CSMD1 are implicated in a neurodevelopmental disorder with intellectual disability and variable cortical malformations

Fig. 2

A CSMD1 linear protein map with inherited missense variants identified in individuals with NDD. Stars denote inherited CSMD1 variants not included in our study cohort but previously published. All variants identified by exome and genome sequencing in affected individuals localize to the CUB (blue) and sushi (green) domains of CSMD1. B Model of CSMD1 protein structure with mapped clinical variants. Each Cub and Sushi domain was individually modeled using AlphaFold2, and then assembled using DeepAsembly to build the complete CSMD1 structure. Protein domains and variant residues were illustrated using color and licorice functions in PyMOL v2.5.2. C Species conservation of affected residues. D Rooted phylogenetic tree of CSMD family proteins and the complement regulator SUSD4 as an outgroup (left). Branches are labeled with genetic distance as measured by substitutions per site. Scale bar, 0.2 substitutions per site. Heatmap illustrating percent sequence identity of SUSD4 and CSMD family proteins to each other determined from protein alignment (right).

Back to article page