SETD5

Description

The SETD5 (SET domain containing 5) is a protein-coding gene located on chromosome 3.

SETD5 is a protein encoded by the SETD5 gene in humans. It belongs to the histone lysine methyltransferase family. Overexpression of SETD5 is linked to increased breast cancer progression. Mutations in SETD5 are associated with a rare developmental disorder known as autosomal dominant mental retardation-23 (MRD23), characterized by various congenital defects and facial abnormalities. Symptoms include developmental delay, intellectual disability, chewing difficulties, hypospadias, and cryptorchidism in males, often accompanied by craniofacial dysmorphisms.

SETD5 plays a crucial role in brain development by regulating RNA elongation rate, which in turn influences neural stem cell proliferation and synaptic transmission. It achieves this by trimethylating Lys-36 of histone H3 (H3K36me3), a modification essential for timely RNA elongation. Additionally, SETD5 monomethylates Lys-9 of histone H3 (H3K9me1) in vitro, though the significance of its histone methyltransferase activity is still debated.

SETD5 is also known as MRD23, SETD5A.

Associated Diseases

• Intellectual developmental disorder, autosomal dominant 23
• Intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency