| Summary: | Sulfate is essential for healthy fetal growth and development. Cysteine dioxygenase type 1 (CDO1) plays an important role in the catabolism of cysteine to sulfate. Cdo1 knockout mice exhibit severe and lethal fetal phenotypes but the involvement of CDO1 gene variants in human development is unknown. We searched the NCBI and Ensembl gene databases and identified four alternatively spliced CDO1 coding mRNA transcripts, as well as 148 validated CDO1 gene variants, including 138 missense, 6 nonsense, 1 frameshift, 1 in-frame deletion, and 2 splice site variants. In silico analyses predicted 68 of the missense variants to be deleterious to CDO1 protein structure and function. We examined the relative abundance of the four CDO1 coding mRNA transcripts in human term placentas using qRT-PCR. CDO1 mRNA variant 2 was the most abundant transcript, with intermediate levels of variant 4 and lower levels of variants 1 and 3. Using in situ hybridization, we localised CDO1 mRNA expression to the syncytiotrophoblast layer of human term placenta. To investigate the regulation of CDO1 gene expression, we analysed the transcriptional activity of the human CDO1 5′-flanking region in the JEG-3 placental cell line using luciferase reporter assays. Transcriptional activities were identified in the regions −5 to −269 and − 269 to −1200 nucleotides upstream of the CDO1 transcription initiation site. Mutational analyses of a single nucleotide polymorphism -289C > G that is common in the general population (allele frequency = 0.37) and a putative transcription factor binding motif (CCAAT enhancer binding protein beta) did not alter transcriptional activity of the CDO1 5′-flanking region. Collectively, this study provides an overview and analysis of human CDO1 for future investigations of this gene in human health. Keywords: Sulfate, Isoform, Splice variant, Placenta, Mutation
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