PMC9452832_01
The Chinese patient's pedigree.
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F1
The other two siblings were healthy and proteinuria was not found (Figure 1).
The results of Sanger sequencing (ACTN4 variant was marked with red arrows).
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F2
Sanger sequencing (Figure 2). Silico predictive algorithms (SIFT, PolyPhen-2, REVEL, MutPred, MutationTaster, PROVEAN, and MVP) of pathogenicity all showed damage.
In total, 30 amino acids surrounding the variant position (marked with a black box).
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F3
The analysis of conserved sequences suggested this variant was located in highly conserved sequences across several mammalian species (Figure 3).
The schematic diagram of ACTN4 variants and ACTN4 protein's domains (UniProtKB-O43707). The patient's ACTN4 variant was marked with a red box.
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F4
The variant c.494C > T (p.A165V) was located in a critical and well-established functional domain (the calponin-homology domain of ACTN4 protein) without benign variants (Figure 4).
Prediction of interatomic interactions of p.A165V (A,B) and p.G195D (C,D). Residues 165 and 195 in the wild-type and mutant proteins (p.A165V and p.G195D) are colored in light green and are shown as sticks. The respective chemical interactions are labeled as dotted lines and colored as follows: hydrogen bonds:(red), weak hydrogen bonds:(orange), hydrophobic contacts:(green), amide-amide contacts:(blue), and ionic interactions:(gold). Amino acid residues are also colored according to type, namely; nitrogen (blue), oxygen (red), and sulfur (yellow). In comparison with wild-type sites, some interactions were observed to be added in mutant sites.
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F5
The residues 165 and 195 in the wild-type were observed to form residue interactions (colored in light green) with their surrounding residues, whereas some interactions were seen to be increased in mutant sites (p.A165V and p.G195D) (Figure 5).