TDO2 was first reported in relation to autosomal recessive hypertryptophanemia in 2017 (Ferreira P, et al., 2017, PMID: 28285122). It results in the biochemical phenotype of persistent hypertryptophanemia and hyperserotoninemia, but without any discernable clinical phenotype. Unbiased ascertainment by newborn screening strongly suggests that this is a benign biochemical variant of no clinical significance (PMIDs: 28285122). Evidence supporting this gene-disease relationship includes case-level data and experimental data. Two unique variants (missense and frameshift) have been reported in the single human case (PMID: 28285122). This gene-disease association is supported by its biochemical function in tryptophan metabolism (PMID: 18027945) and a knockout mouse model (PMID: 19323847). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship.
This gene-disease pair was previously evaluated by the Aminoacidopathy GCEP on 07/10/2020. It was reevaluated on 10/24/2023. As a result of this reevaluation, the classification remained Limited with no new evidence identified.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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