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Reviewed August 2014

What is the official name of the SMCHD1 gene?

The official name of this gene is “structural maintenance of chromosomes flexible hinge domain containing 1.”

SMCHD1 is the gene's official symbol. The SMCHD1 gene is also known by other names, listed below.

Read more about gene names and symbols on the About page.

What is the normal function of the SMCHD1 gene?

The SMCHD1 gene provides instructions for making a protein that is involved in regulating gene activity by altering the structure of DNA. Specifically, the SMCHD1 protein plays a role in DNA methylation, which is the addition of methyl groups (consisting of one carbon atom and three hydrogen atoms) to DNA molecules. The addition of methyl groups turns off (silences) genes, so hypermethylated regions of DNA tend to have fewer genes that are turned on (active).

The SMCHD1 protein is involved in a process called X-inactivation or Lyonization. Early in embryonic development in females, one of the two X chromosomes is randomly and permanently inactivated in cells other than egg cells. X-inactivation ensures that females, like males, have only one active copy of the X chromosome in each body cell. The SMCHD1 protein helps to inactivate the X chromosome by hypermethylating certain areas of DNA called CpG islands. The protein then remains attached (bound) to the inactive X chromosome to help keep it inactivated throughout life.

The SMCHD1 protein also plays a role in hypermethylation of a region near the end of chromosome 4 called D4Z4. This region consists of 11 to more than 100 repeated segments, each of which is about 3,300 DNA base pairs (3.3 kb) long. The segment closest to the end of chromosome 4 contains a gene called DUX4. Because the D4Z4 region is hypermethylated, the DUX4 gene is silenced in most adult cells and tissues. Little is known about the function of the protein produced from the DUX4 gene; it appears to help control the activity of other genes.

Studies suggest that the SMCHD1 gene is also involved in repairing damaged DNA. However, little is known about its role in this process.

How are changes in the SMCHD1 gene related to health conditions?

facioscapulohumeral muscular dystrophy - caused by mutations in the SMCHD1 gene

More than a dozen mutations in the SMCHD1 gene have been found to cause facioscapulohumeral muscular dystrophy, a disorder characterized by muscle weakness and wasting (atrophy) that worsens slowly over time. Two forms of the disorder have been described: type 1 (FSHD1) and type 2 (FSHD2). Changes in the SMCHD1 gene appear to play a role in both types.

SMCHD1 gene mutations cause most cases of FSHD2. These mutations reduce the amount of SMCHD1 protein available to add methyl groups to the D4Z4 region. The resulting hypomethylation of this region prevents the DUX4 gene from being silenced in cells and tissues where it is usually turned off, such as adult muscle cells. However, hypomethylation of the D4Z4 region results in facioscapulohumeral muscular dystrophy only when it occurs in people who also have at least one copy of chromosome 4 that is described as "permissive." A "permissive" chromosome 4 has a functional region of DNA known as a pLAM sequence located next to the DUX4 gene. The pLAM sequence is necessary for the production of the DUX4 protein. (Conversely, a "non-permissive" chromosome 4 does not contain a functional pLAM sequence, preventing the production of any DUX4 protein.) Researchers believe that the DUX4 protein influences the activity of other genes, particularly in muscle cells. However, it is unknown how the presence of this protein damages or destroys these cells, leading to progressive muscle weakness and atrophy.

Studies suggest that mutations in the SMCHD1 gene can increase the severity of disease in people with the other type of facioscapulohumeral muscular dystrophy, FSHD1. FSHD1 results when the D4Z4 region is abnormally shortened (contracted), containing between 1 and 10 repeats instead of the usual 11 to 100 repeats. Researchers suspect that the combination of a contracted D4Z4 region and a SMCHD1 gene mutation causes the D4Z4 region to have even fewer methyl groups attached, which allows the DUX4 gene to be highly active. In people with both genetic changes, the overactive gene leads to severe muscle weakness and atrophy.

Where is the SMCHD1 gene located?

Cytogenetic Location: 18p11.32

Molecular Location on chromosome 18: base pairs 2,655,887 to 2,805,017

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBIThis link leads to a site outside Genetics Home Reference.)

The SMCHD1 gene is located on the short (p) arm of chromosome 18 at position 11.32.

The SMCHD1 gene is located on the short (p) arm of chromosome 18 at position 11.32.

More precisely, the SMCHD1 gene is located from base pair 2,655,887 to base pair 2,805,017 on chromosome 18.

See How do geneticists indicate the location of a gene? in the Handbook.

Where can I find additional information about SMCHD1?

You and your healthcare professional may find the following resources about SMCHD1 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the SMCHD1 gene or gene products?

  • KIAA0650
  • SMC hinge domain-containing protein 1
  • structural maintenance of chromosomes flexible hinge domain-containing protein 1

Where can I find general information about genes?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding SMCHD1?

atom ; atrophy ; cell ; chromatin ; chromosome ; CpG islands ; DNA ; DNA base ; domain ; egg ; embryonic ; epigenetic ; gene ; kb ; lyonization ; methyl ; methylation ; muscle cells ; muscular dystrophy ; mutation ; protein ; wasting ; X-inactivation

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

See also Understanding Medical Terminology.

References (8 links)


The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

Reviewed: August 2014
Published: February 1, 2016