SYNPO was first reported in relation to autosomal dominant glomerulopathy in 2010 (Dai et al., PMID: 19666657). Two variants (at the promoter site) that have been reported in 2 probands in one publication (PMID: 19666657) are included in this curation. A second publication details an affected individual with a homozygous missense variant, although heterozygous familial carriers are unaffected (PMID: 33615071). The mechanism of pathogenicity appears to be loss of function. This gene-disease relationship is also supported by expression in podocytes, interaction with CD2AP, and a knockout model demonstrating conditionally stimulated nephrotic syndrome along with podocytes showing impaired actin filament reformation in vitro (PMIDs: 15841212, 16628251, 33615071). 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 classification was approved by the ClinGen Glomerulopathy GCEP on the meeting date November 13, 2023 (SOP Version 10).
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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