KDM6B encodes a histone demethylase that plays key roles in the regulation of gene expression during development. Homozygous KDM6B variants (missense, splice region, and in-frame deletion) have been reported in three consanguineous families with syndromic intellectual disability (ID) (PMIDs: 21937992, 26077850, 28097321). Affected individuals present with moderate to severe ID, dysmorphic facial features, and mild hand and feet anomalies. Functional studies were not performed to assess the pathogenicity of these variants. Heterozygous de novo KDM6B variants cause autosomal dominant syndromic ID; this disease association has been curated separately.
In summary, there is limited evidence to support the relationship between KDM6B and autosomal recessive syndromic ID. 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 Intellectual Disability and Autism Gene Curation Expert Panel on February 18 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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