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Review
. 2021 Oct 27;22(21):11593.
doi: 10.3390/ijms222111593.

Pathogenic Variants in Selenoproteins and Selenocysteine Biosynthesis Machinery

Didac Santesmasses  1 , Vadim N Gladyshev  1
Affiliations
Review

Pathogenic Variants in Selenoproteins and Selenocysteine Biosynthesis Machinery

Didac Santesmasses et al. Int J Mol Sci. .

Abstract

Selenium is incorporated into selenoproteins as the 21st amino acid selenocysteine (Sec). There are 25 selenoproteins encoded in the human genome, and their synthesis requires a dedicated machinery. Most selenoproteins are oxidoreductases with important functions in human health. A number of disorders have been associated with deficiency of selenoproteins, caused by mutations in selenoprotein genes or Sec machinery genes. We discuss mutations that are known to cause disease in humans and report their allele frequencies in the general population. The occurrence of protein-truncating variants in the same genes is also presented. We provide an overview of pathogenic variants in selenoproteins genes from a population genomics perspective.

Keywords: genetic variance; human disease; selenium; selenocysteine; selenoprotein.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Pathogenic variants and protein-truncating variants in SELENON. (a) Genomic organization of SELENON exons, and location of ClinVar pathogenic variants (above) and gnomAD protein-truncating variants (PTV) (below). The shape and color of each variant corresponds to its predicted consequence (see legend). For gnomAD variants only, the size of the symbol is proportional to the allele frequency. The genomic notation is used to describe each variant. (b) Location of variants along the SELENON protein sequence. The length of the protein is indicated on the right. Vertical black lines correspond to exon boundaries, and the vertical orange line correspond to the Sec residue. The same aesthetics for variants as (a) are used. The genomic coordinates correspond to genome build GRCh37/hg19; the SELENON gene structure and protein sequence correspond to transcript ENST00000374315.
Figure 2
Figure 2
Pathogenic variants and protein-truncating variants in GPX4. Location of ClinVar pathogenic variants (above) and gnomAD protein-truncating variants (below), along the GPX4 protein sequence. The same aesthetics as in Figure 1b are used. GPX4 transcript: ENST00000354171.
Figure 3
Figure 3
Pathogenic variants and protein-truncating variants in TXNRD1 and TXNRD2. Location of pathogenic variants (above) and gnomAD protein-truncating variants (below) along the TXNRD1 and TXNRD2 protein sequence. The same aesthetics as Figure 1b are used. TXNRD1 transcript: ENST00000526390; TXNRD2 transcript: ENST00000400521.
Figure 4
Figure 4
Pathogenic variants and protein-truncating variants in SELENOI. Location of ClinVar pathogenic variants (above) and gnomAD protein-truncating variants (below), along the SELENOI protein sequence. The same aesthetics as Figure 1b are used. SELENOI transcript: ENST00000260585.
Figure 5
Figure 5
Pathogenic variants and protein-truncating variants in SECISBP2. Location of ClinVar pathogenic variants (above) and gnomAD protein-truncating variants (below), along the SECISBP2 protein sequence. The same aesthetics as Figure 1b are used. SECISBP2 transcript: ENST00000375807.
Figure 6
Figure 6
Pathogenic variants and protein-truncating variants in SEPSECS. Location of ClinVar pathogenic variants (above) and gnomAD protein-truncating variants (below) along the SEPSECS protein sequence. The same aesthetics as Figure 1b are used. SEPSECS transcript: ENST00000382103.
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