HOGA1 was first reported in relation to autosomal recessive Primary Hyperoxaluria III (HP3) in 2010 (Belostotsky et al., PMID: 20797690). 17 variants (missense, in-frame indel, splicing, frameshift, nonsense) that have been reported in 16 probands in 5 publications (PMIDs: 20797690, 21896830, 22391140, 28711958, 31123811) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached, The mechanism of disease appears to be loss-of-function. This gene-disease relationship is also supported by experimental evidence (expression-level evidence; GTEx and Humphrey’s Lab expression data). A mouse model was evaluated, but was not scored as the mice lacked urinary oxalate excretion, a key part of the human phenotype. In summary, there is definitive evidence supporting the relationship between HOGA1 and autosomal recessive HP3. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Tubulopathy GCEP on the meeting date 5/30/2024 (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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