EDARADD gene

EDAR associated via death domain

Normal Function

The EDARADD gene provides instructions for making a protein called the EDAR-associated via death domain (EDARADD) 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.

Health Conditions Related to Genetic Changes

Hypohidrotic ectodermal dysplasia

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.

More About This Health Condition

Other Names for This Gene

ectodysplasia A receptor associated death domain
ectodysplasin A receptor associated adapter protein
EDAD_HUMAN
EDAR-associated death domain

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Tests of EDARADD

Scientific Articles on PubMed

PubMed

Catalog of Genes and Diseases from OMIM

EDAR-ASSOCIATED DEATH DOMAIN; EDARADD

Gene and Variant Databases

References

Chassaing N, Cluzeau C, Bal E, Guigue P, Vincent MC, Viot G, Ginisty D, Munnich A, Smahi A, Calvas P. Mutations in EDARADD account for a small proportion of hypohidrotic ectodermal dysplasia cases. Br J Dermatol. 2010 May;162(5):1044-8. doi: 10.1111/j.1365-2133.2010.09670.x. Epub 2010 Mar 5. Citation on PubMed
Chaudhary AK, Girisha KM, Bashyam MD. A novel EDARADD 5'-splice site mutation resulting in activation of two alternate cryptic 5'-splice sites causes autosomal recessive Hypohidrotic Ectodermal Dysplasia. Am J Med Genet A. 2016 Jun;170(6):1639-41. doi: 10.1002/ajmg.a.37607. Epub 2016 Mar 15. No abstract available. Citation on PubMed
Cluzeau C, Hadj-Rabia S, Jambou M, Mansour S, Guigue P, Masmoudi S, Bal E, Chassaing N, Vincent MC, Viot G, Clauss F, Maniere MC, Toupenay S, Le Merrer M, Lyonnet S, Cormier-Daire V, Amiel J, Faivre L, de Prost Y, Munnich A, Bonnefont JP, Bodemer C, Smahi A. Only four genes (EDA1, EDAR, EDARADD, and WNT10A) account for 90% of hypohidrotic/anhidrotic ectodermal dysplasia cases. Hum Mutat. 2011 Jan;32(1):70-2. doi: 10.1002/humu.21384. Citation on PubMed
Headon DJ, Emmal SA, Ferguson BM, Tucker AS, Justice MJ, Sharpe PT, Zonana J, Overbeek PA. Gene defect in ectodermal dysplasia implicates a death domain adapter in development. Nature. 2001 Dec 20-27;414(6866):913-6. doi: 10.1038/414913a. Citation on PubMed
Wohlfart S, Hammersen J, Schneider H. Mutational spectrum in 101 patients with hypohidrotic ectodermal dysplasia and breakpoint mapping in independent cases of rare genomic rearrangements. J Hum Genet. 2016 Oct;61(10):891-897. doi: 10.1038/jhg.2016.75. Epub 2016 Jun 16. Citation on PubMed
Wohlfart S, Soder S, Smahi A, Schneider H. A novel missense mutation in the gene EDARADD associated with an unusual phenotype of hypohidrotic ectodermal dysplasia. Am J Med Genet A. 2016 Jan;170A(1):249-53. doi: 10.1002/ajmg.a.37412. Epub 2015 Oct 5. Citation on PubMed
Wright JT, Grange DK, Fete M. Hypohidrotic Ectodermal Dysplasia. 2003 Apr 28 [updated 2025 Mar 20]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1112/ Citation on PubMed

Genomic Location

The EDARADD gene is found on chromosome 1.

MEDICAL ENCYCLOPEDIA

Understanding Genetics

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