GSTZ1 was first reported in relation to autosomal recessive maleylacetoacetate isomerase deficiency in 2017 (Yang et al., 2017; PMID 27876694). The GSTZ1 gene encodes an enzyme that is involved in the phenylalanine/phenylacetate degradation pathway. Most patients with the deficiency show only mild symptoms and remain well without treatment (Yang et al., 2017; PMID 27876694). Five variants (missense, nonsense, and intronic) that have been reported in seven probands in two publications (PMIDs: 27876694, 38535121) are included in this curation. This gene-disease association is also supported by biochemical assays and a mouse model (PMIDs: 12052898, 9417084). 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 originally evaluated by the ClinGen Aminoacidopathy Gene Curation Expert Panel on March 22nd, 2019. It was reevaluated on September 9th, 2022, and on December 5th, 2024. As a result of this reevaluation, new genetic evidence was added (PMID: 38535121) but the classification did not change.
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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