EDAR associated death domain

The EDARADD gene provides instructions for making a protein called the EDAR-associated death domain protein. This protein is part of a signaling pathway that plays an important role in development before birth. Specifically, it is critical for interactions between two embryonic cell layers called the ectoderm and the mesoderm. In the early embryo, these cell layers form the basis for many of the body's organs and tissues. Ectoderm-mesoderm interactions are essential for the formation of several structures that arise from the ectoderm, including the skin, hair, nails, teeth, and sweat glands.

The EDARADD protein interacts with another protein, called the ectodysplasin A receptor, which is produced from the EDAR gene. This interaction occurs at a region called the death domain that is present in both proteins. The EDARADD protein acts as an adapter, which means it assists the ectodysplasin A receptor in triggering chemical signals within cells. These signals affect cell activities such as division, growth, and maturation. Starting before birth, this signaling pathway controls the formation of ectodermal structures such as hair follicles, sweat glands, and teeth.

Fewer than 10 mutations in the EDARADD gene have been found to cause hypohidrotic ectodermal dysplasia, the most common form of ectodermal dysplasia. Starting before birth, ectodermal dysplasias result in the abnormal development of the skin, hair, nails, teeth, and sweat glands. Hypohidrotic ectodermal dysplasia is characterized by a reduced ability to sweat (hypohidrosis), sparse scalp and body hair (hypotrichosis), and several missing teeth (hypodontia) or teeth that are malformed. EDARADD gene mutations are an infrequent cause of hypohidrotic ectodermal dysplasia, accounting for only about 1 percent of all cases.

Most of the EDARADD gene mutations associated with hypohidrotic ectodermal dysplasia change single protein building blocks (amino acids) in the receptor protein. These changes occur in or near the death domain, preventing the EDARADD protein from interacting effectively with the ectodysplasin A receptor. As a result, the receptor cannot trigger the signals needed for ectoderm-mesoderm interactions in early development. Without these signals, hair follicles, teeth, sweat glands, and other ectodermal structures do not form properly, which leads to the characteristic features of hypohidrotic ectodermal dysplasia.

Cytogenetic Location: 1q42.3-q43, which is the long (q) arm of chromosome 1 between positions 42.3 and 43

Molecular Location: base pairs 236,394,286 to 236,484,930 on chromosome 1 (Homo sapiens Updated Annotation Release 109.20200228, GRCh38.p13) (NCBI)

Cytogenetic Location: 1q42.3-q43, which is the long (q) arm of chromosome 1 between positions 42.3 and 43
  • ectodysplasia A receptor associated death domain
  • ectodysplasin A receptor associated adapter protein
  • EDAR-associated death domain