RAB23 was first reported in relation to autosomal recessive Carpenter syndrome as early as 2007 (Jenkins et al., PMID: 17503333). At least nine variants (nonsense, frameshift, splice site, in-frame indel, missense) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data, segregation data, and experimental data. This curation includes five variants reported in five probands to reach a maximum score of 12 points for genetic evidence (PMID: 17503333, 20358613, 23599695, 25168863, 33368989). Variants in this gene segregated with disease in 5 additional family members. More evidence is available in the literature (PMID: 24458945, 21412941). The mechanism of pathogenicity is proposed to be loss of function (PMID: 21412941). This gene-disease relationship is also supported by animal models, expression studies, and in vitro functional assays (PMID: 32662771, 18218620). In summary, there is definitive evidence to support the relationship between RAB23 and autosomal recessive Carpenter syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This curation was approved by the Craniofacial Malformations Gene Curation Expert Panel on 4/22/21 (SOP Version 8).
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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