TULP3 was first reported in relation to autosomal recessive ciliopathy in 2022 (Devane et al., PMID: 35397207). At least eight variants (missense, nonsense, frameshift, intragenic deletion, splice site) that have been reported in eight probands and additional family members in a publication (PMID: 35397207) are included in this curation. Variants in this gene segregated with disease in three additional family members. Evidence supporting this gene-disease relationship includes case-level, segregation data, and experimental data. The mechanism of pathogenicity appears to be lodd of function (LOF). Animal models, with data from mice (Legue et al., 2019; PMID: 30799240 and Hwang et al., 2019; PMID: 30799239) and zebrafish models (Devane et al., 2022; PMID: 35397207), and expression studies also support this gene-disease relationship (PMIDs: 35397207, 30799240, 30799239, 9828123). In summary, there is strong evidence to support the relationship between TULP3 and autosomal recessive ciliopathy. Three years must elapse from the first proposal of the relationship to reach a definitive classification without any valid contradictory evidence. We will re-evaluate this gene-disease relationship at that time to determine if an upgraded classification of definitive is warranted. This classification was approved by the ClinGen Kidney Cystic and Ciliopathy Disorders GCEP on the meeting date 07/27/2022 (SOP Version 9).
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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