See Table A. Genes and Databases for chromosome locus and protein.

See Molecular Genetics for information on variants detected in this gene.

A number of additional individuals with contiguous gene deletions (not included in these calculations) have been reported (see Genetically Related Disorders).

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

In individuals with biochemically confirmed OTC deficiency (i.e., elevated urinary orotate, a positive allopurinol test, reduced OTC enzyme activity in liver biopsy, or a combination of these findings) [Caldovic et al 2015]

Data derived from Caldovic et al [2015] and publicly available databases of OTC sequence variants (ClinVar and LOVD)

Disease-causing variants in OTC regulatory regions [Jang et al 2018] and deep intronic regions [Kumar et al 2021] have been identified in individuals with biochemically confirmed OTC deficiency.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Gene-targeted deletion/duplication testing will detect deletions ranging from a single exon to the whole gene; however, breakpoints of large deletions and/or deletion of adjacent genes (e.g., those described in Deardorff et al [2008], Di Stefano et al [2015]) and Gallant et al [2015]) may not be detected by these methods.

When sequence analysis was followed by deletion/duplication analysis, a molecular defect was detected in 80%-90% of affected individuals with biochemically confirmed OTC deficiency [Tuchman et al 2008, Shchelochkov et al 2009, Caldovic et al 2015]. Other loci associated with an OTC deficiency phenotype have not been identified. However, disease-causing variants located in the deep intronic region or regulator regions have been subsequently identified in individuals with negative results on previous genetic testing [Jang et al 2018, Kumar et al 2021].