Figure 1.

Compound-heterozygous mutations in NUP160, NUP160^Glu803Lys and NUP160^Arg1173X, were identified in an autosomal recessive family with steroid-resistant nephrotic syndrome. (A) Human NUP160 cDNA (NM_015231.2; 5476 bp) showing exons (numbered; alternating black and white), positions of start (ATG) and stop (TGA) codons, and mutation sites (arrows). (B) Human Nup160 protein (NP_056046.1; 1436 amino acids) structural domains, phosphorylation sites, and locations of missense (amino acid 803) and truncation (amino acid 1173) lesions. (C) A pedigree of the affected family (family members diagnosed with kidney disease are indicated in black). The arrow indicates the proband. (D) Compound-heterozygous missense and truncating NUP160 mutations identified from proband (II6; patient [P]) sequencing. Nucleotide and corresponding amino acid sequences are shown for wild-type (upper panel; in black) and mutant (lower panel; in green) alleles. Codons are underlined (green), and altered nucleotides and amino acids are highlighted (red). Arrows indicate positions of mutations in relation to exons and protein motifs (in A and B, respectively). Relevant sequences from surviving family members (I1, father [F]; I2, mother [M]; II5, sister [S]) are also shown. (E) Phylogenetic comparisons of amino acid sequences of Nup160 protein regions affected by the identified mutations.