KDM6A gene

lysine demethylase 6A

The KDM6A gene provides instructions for making an enzyme called lysine-specific demethylase 6A that is found in many organs and tissues of the body. Lysine-specific demethylase 6A functions as a histone demethylase. Histone demethylases are enzymes that modify proteins called histones. Histones are structural proteins that attach (bind) to DNA and give chromosomes their shape. By removing a molecule called a methyl group from histones (a process called demethylation), histone demethylases control (regulate) the activity of certain genes. Lysine-specific demethylase 6A appears to regulate certain genes that are important for development.

Lysine-specific demethylase 6A is also believed to act as a tumor suppressor, which means it normally helps prevent cells from growing and dividing in an uncontrolled way.

At least 35 mutations in the KDM6A gene have been identified in people with Kabuki syndrome, a disorder characterized by distinctive facial features, intellectual disability, and abnormalities affecting other parts of the body.

Most of the KDM6A gene mutations associated with Kabuki syndrome delete genetic material in the KDM6A gene sequence or result in a premature stop signal that leads to an abnormally short lysine-specific demethylase 6A enzyme. As a result of these mutations, the enzyme is nonfunctional. A lack of functional lysine-specific demethylase 6A enzyme disrupts its role in histone demethylation and impairs proper regulation of certain genes in many of the body's organs and tissues, resulting in the abnormalities of development and function characteristic of Kabuki syndrome.

Although lysine-specific demethylase 6A is believed to act as a tumor suppressor, a loss of this enzyme's function does not seem to increase cancer risk in people with Kabuki syndrome.

Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Somatic mutations in the KDM6A gene have been found in some cases of bladder cancer. Bladder cancer is a disease in which certain cells in the bladder become abnormal and multiply uncontrollably to form a tumor. Bladder cancer may cause blood in the urine, pain during urination, frequent urination, the feeling to of needing to urinate without being able to, or lower back pain.

Bladder cancer is generally divided into two types, non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), based on where in the bladder the tumor is located. About half of NMIBC tumors have KDM6A gene mutations. These KDM6A gene mutations change single protein building blocks (amino acids) in the enzyme, which appears to impair the enzyme's role in histone demethylation. As a result, regulation of certain genes in bladder cells is disrupted, which likely leads to uncontrolled cell division and the formation of bladder cancer.

Somatic mutations in the KDM6A gene have been identified in cancers of the breast, esophagus, colon, kidney, and brain, and cancers of blood-forming cells called myeloid leukemia and multiple myeloma. Most of these mutations result in an abnormally short, nonfunctional lysine-specific demethylase 6A enzyme that cannot perform its role as a tumor suppressor, resulting in the development of cancer.

Cytogenetic Location: Xp11.3, which is the short (p) arm of the X chromosome at position 11.3

Molecular Location: base pairs 44,873,175 to 45,112,779 on the X chromosome (Homo sapiens Updated Annotation Release 109.20200522, GRCh38.p13) (NCBI)

Cytogenetic Location: Xp11.3, which is the short (p) arm of the X chromosome at position 11.3
  • bA386N14.2
  • bA386N14.2 (ubiquitously transcribed X chromosome tetratricopeptide repeat protein (UTX))
  • histone demethylase UTX
  • KABUK2
  • lysine (K)-specific demethylase 6A
  • lysine-specific demethylase 6A
  • ubiquitously transcribed tetratricopeptide repeat protein X-linked
  • ubiquitously-transcribed TPR gene on the X chromosome
  • ubiquitously-transcribed TPR protein on the X chromosome
  • UTX