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Reviewed August 2014

What is the official name of the DUX4 gene?

The official name of this gene is “double homeobox 4.”

DUX4 is the gene's official symbol. The DUX4 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 DUX4 gene?

The DUX4 gene is located near the end of chromosome 4 in a region known as 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 entire D4Z4 region is normally hypermethylated, which means that it has a large number of methyl groups (consisting of one carbon atom and three hydrogen atoms) attached to the DNA. The addition of methyl groups turns off (silences) genes, so hypermethylated regions of DNA tend to have fewer genes that are turned on (active).

Each of the repeated segments in the D4Z4 region contains a copy of the DUX4 gene; the copy closest to the end of chromosome 4 is called DUX4, while the other copies are described as "DUX4-like" or DUX4L. Hypermethylation of the D4Z4 region keeps the DUX4-like genes silenced all the time. No protein is produced from these genes. The DUX4 gene is also silenced in most adult cells and tissues, although it is active during early development and in the testes of adult males. Little is known about the function of the protein produced from the active DUX4 gene; it appears to help control the activity of other genes.

The DUX4 gene (the copy closest to the end of chromosome 4) is located next to a regulatory region of DNA known as a pLAM sequence, which is necessary for the production of the DUX4 protein. Some copies of chromosome 4 have a functional pLAM sequence, while others do not. Copies of chromosome 4 with a functional pLAM sequence are described as 4qA or "permissive." Those without a functional pLAM sequence are described as 4qB or "non-permissive." Without a functional pLAM sequence, no DUX4 protein is made. Because there are two copies of chromosome 4 in each cell, individuals may have two "permissive" copies of chromosome 4, two "non-permissive" copies, or one of each.

Does the DUX4 gene share characteristics with other genes?

The DUX4 gene belongs to a family of genes called homeobox (homeoboxes).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? in the Handbook.

How are changes in the DUX4 gene related to health conditions?

facioscapulohumeral muscular dystrophy - associated with the DUX4 gene

Changes in the D4Z4 region of chromosome 4, which contains the DUX4 gene, cause facioscapulohumeral muscular dystrophy. This disorder is characterized by muscle weakness and wasting (atrophy) that worsens slowly over time. Two types of the disorder have been described: type 1 (FSHD1) and type 2 (FSHD2). Both types result from hypomethylation of the D4Z4 region, in which the DNA has fewer methyl groups attached than normal. In FSHD1, hypomethylation occurs because the D4Z4 region is abnormally shortened (contracted), containing between 1 and 10 repeats instead of the usual 11 to 100 repeats. In FSHD2, hypomethylation most often results from mutations in a gene called SMCHD1, which normally hypermethylates the D4Z4 region.

Hypomethylation of the D4Z4 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 with a "permissive" chromosome 4. The "permissive" chromosome contains a working pLAM sequence, which allows protein to be produced from the abnormally active DUX4 gene. Researchers believe that the protein influences the activity of other genes, particularly in muscle cells. However, it is unknown how presence of the DUX4 protein damages or destroys these cells, leading to progressive muscle weakness and atrophy.

Where is the DUX4 gene located?

Cytogenetic Location: 4

Molecular Location on chromosome 4: base pairs 190,173,669 to 190,175,845

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

The DUX4 gene is located on chromosome 4.

The DUX4 gene is located on chromosome 4.

More precisely, the DUX4 gene is located from base pair 190,173,669 to base pair 190,175,845 on chromosome 4.

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

Where can I find additional information about DUX4?

You and your healthcare professional may find the following resources about DUX4 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 DUX4 gene or gene products?

  • double homeobox 4-like
  • double homeobox protein 4
  • double homeobox protein 4/10
  • double homeobox protein 10

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 DUX4?

atom ; atrophy ; cell ; chromatin ; chromosome ; DNA ; DNA base ; epigenetic ; gene ; homeobox ; homeodomain ; kb ; methyl ; muscle cells ; muscular dystrophy ; protein ; testes ; wasting

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