SUGCT was first reported in relation to autosomal recessive glutaric acidemia type 3 in 2008 (Sherman EA, et al., 2008, PMID: 18926513). SUGCT catalyzes the succinyl-CoA-dependent conversion of glutaric acid into glutaryl-CoA preventing urinary loss of the organic acid; in patients with deficiency of SUGCT there is a consequent accumulation of glutaric acid. Glutaric aciduria type 3 is a biochemical phenotype with uncertain clinical relevance. Evidence supporting the relationship between SUGCT and glutaric acidemia type 3 includes case-level data and experimental data. Variants in this gene have been reported in at least 12 probands in 6 publications (PMIDs: 18926513, 28766179, 29421601, 2779420, 37920852, 39101156). At least 7 unique missense, nonsense, and frameshift variants have been reported in humans. This gene-disease relationship is supported by the biochemical function of SUGCT which is consistent with the biochemical abnormalities observed in individuals with glutaric acidemia type 3 (PMID: 23893049) and the biochemical features of a Sugct knockout mouse (PMID: 31722069). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged.
This gene-disease pair was previously evaluated by the Aminoacidopathy GCEP on 09/25/2020. It was reevaluated on 10/14/2022 and 12/10/2024 which identified three additional cases (PMIDs: 37920852, 39101156). As a result of this reevaluation, the classification remained Moderate.
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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