KDM5B was first reported in relation to autosomal recessive intellectual disability in 2018 (Faundes, et al., PMID: 29276005). At least 9 unique variants (e.g. missense, nonsense, frameshift, splice site, large deletion, etc.) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data, and experimental evidence. Variants in this gene have been reported in at least 5 probands in 3 publications (PMIDs: 29276005, 34573379, 30409806). Nine variants (missense, nonsense, frameshift, splice site, large deletion) that have been reported in 5 probands in 3 publications (PMIDs: 29276005, 34573379, 30409806) are included in this curation. Please note that due to limitations of the scoring interface, a proband who was compound heterozygous for a splice variant and a large deletion was not able to be formally entered and scored at 2 points (PMID:30409806).
This gene-disease association is also supported by animal models, in vitro functional assays, and biochemical function studies (PMIDs: 30409806, 22020125). Of note, this gene has also been implicated in autosomal dominant intellectual disability, autism, and development disorder. These will be assessed separately.
Although this curation reached Definitive, the classification has been modified to Moderate due to the small number of probands reported in the literature. More evidence is needed to establish this relationship definitively. In summary, there is moderate evidence to support this gene-disease relationship. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on 3/1/2022 (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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