KDM6B
Description
The KDM6B (lysine demethylase 6B) is a protein-coding gene located on chromosome 17.
KDM6B (JMJD3) is a human gene that encodes for the Lysine demethylase 6B protein. It is involved in several key processes, including:
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Regulation during differentiation: KDM6B expression increases during cardiac and endothelial differentiation of mouse embryonic stem cells.
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Small molecule inhibition: GSK-J1, a small molecule inhibitor, has been developed to target the jumonji domain of the KDM6 histone demethylase family, aiming to modulate proinflammatory responses in macrophages.
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Role in pathology: Mutations in the KDM6B gene can cause a neurodevelopmental disorder characterized by coarse facial features and mild skeletal abnormalities. This disorder was first described in 2019 and is identified through standard laboratory exome sequencing.
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Clinical picture: Individuals with KDM6B variants often exhibit developmental delays, distinctive facial features, musculoskeletal abnormalities, neuromuscular hypotonia, intellectual disability, and autism spectrum disorder.
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Epidemiology: De novo alterations in the KDM6B gene are found in approximately 0.12% of patients presenting with intellectual disability and/or developmental delay.
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Related conditions: There are overlapping phenotypic features between KDM6A-associated Kabuki syndrome and KDM6B variations, including prominent ears, abnormal dentition, heart defects, feeding difficulties, cryptorchidism, joint hypermobility, developmental delays, hypotonia, and behavioral issues.
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Ongoing research: Pathologic mutations in KDM6B have been linked to five cases of cerebral folate deficiency.
KDM6B is a histone demethylase that specifically removes methyl groups from lysine 27 of histone H3, playing a crucial role in the histone code. It demethylates both trimethylated and dimethylated H3 Lys-27. KDM6B is essential for regulating posterior development by controlling HOX gene expression. It also participates in the inflammatory response by modulating gene expression and macrophage differentiation during inflammation. Beyond its demethylase activity, KDM6B plays a role in chromatin remodeling, acting as a bridge between T-box factors and the SMARCA4-containing SWI/SNF remodeling complex to regulate T-box family member-dependent gene expression.
KDM6B is also known as JMJD3, NEDCFSA, NEDSST.
