SMCHD1 : structural maintenance of chromosomes flexible hinge domain containing 1

Description

The SMCHD1 (structural maintenance of chromosomes flexible hinge domain containing 1) is a protein-coding gene located on chromosome 18.

The SMCHD1 gene provides instructions for making a protein that regulates gene activity by altering the structure of DNA. This protein is associated with DNA methylation, adding methyl groups to DNA molecules, which often leads to gene silencing. SMCHD1 is involved in X-inactivation, where one X chromosome in females is randomly and permanently inactivated during embryonic development. It hypermethylates CpG islands on the inactive X chromosome, helping to keep it inactivated. SMCHD1 also plays a role in hypermethylation of the D4Z4 region near the end of chromosome 4, silencing the DUX4 gene. This protein appears to contribute to normal development of the nose, eyes, and other head and face structures, and may participate in DNA repair.

SMCHD1 is a non-canonical member of the structural maintenance of chromosomes (SMC) protein family that plays a crucial role in epigenetic silencing by regulating chromatin architecture. It promotes heterochromatin formation in both autosomes and chromosome X, likely by mediating the merging of chromatin compartments. This protein is vital in X chromosome inactivation in females, promoting the spread of heterochromatin. It is recruited to the inactivated X chromosome by Xist RNA, acting by merging chromatin compartments and creating a random chromatin interaction pattern. This process ultimately leads to a compartment-less architecture characteristic of the inactivated X chromosome. Additionally, SMCHD1 is required for Xist RNA spreading. Furthermore, it is essential for silencing a subset of clustered autosomal loci in somatic cells, such as the DUX4 locus. This protein exhibits ATPase activity, suggesting its involvement in structural manipulation of chromatin in an ATP-dependent manner, contributing to its role in gene expression regulation. SMCHD1 also plays a significant role in DNA repair, localizing to sites of DNA double-strand breaks in response to DNA damage to promote repair. It facilitates non-homologous end joining (NHEJ) while inhibiting homologous recombination (HR) repair.

SMCHD1 is also known as BAMS, FSHD2.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing