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    EDAR Gene

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    Submitted by: Vivi Li
    (This entry belongs to Entry Collection "MedlinePlus ")

    Definition

    Ectodysplasin A receptor: The EDAR gene provides instructions for making a protein called the ectodysplasin A receptor. 

    1. Normal Function

    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 ectodysplasin A receptor interacts with a protein called ectodysplasin A1 (produced from the EDA gene). On the cell surface, ectodysplasin A1 attaches to this receptor like a key in a lock. When these two proteins are connected, they trigger a series of chemical signals that 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.

    Studies suggest that common variations (polymorphisms) in the EDAR gene are associated with the thickness and straightness of scalp hair, particularly in East Asian populations. EDAR appears to be one of many genes that influence these hair traits.

    2. Health Conditions Related to Genetic Changes

    2.1 Hypohidrotic Ectodermal Dysplasia

    More than 50 mutations in the EDAR 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. EDAR gene mutations account for about 10 percent of all cases of hypohidrotic ectodermal dysplasia.

    Most of the EDAR gene mutations associated with hypohidrotic ectodermal dysplasia change a single protein building block (amino acid) in the receptor protein. Some of the mutations that cause this condition lead to the production of an abnormal version of the ectodysplasin A receptor. Other mutations prevent cells from producing any functional receptor. All of these genetic changes prevent the receptor from interacting with ectodysplasin A1, which impairs chemical signaling needed for interactions between the ectoderm and the mesoderm 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.

    2.2 Other Disorders

    EDAR gene mutations have also been reported in some people with a condition called nonsyndromic tooth agenesis. This condition causes one or more teeth not to form. Although missing teeth is a common feature of ectodermal dysplasias, "nonsyndromic" suggests that in these cases tooth agenesis occurs without the other signs and symptoms of those conditions. It is unclear why the effects of some mutations in this gene appear to be limited to tooth development, while other mutations affect the formation of multiple ectodermal tissues.

    3. Other Names for This Gene

    • DL

    • ectodysplasin 1, anhidrotic receptor

    • ectodysplasin A1 isoform receptor

    • ectodysplasin receptor

    • ED1R

    • ED3

    • ED5

    • EDA-A1R

    • EDA1R

    • EDA3

    • EDAR_HUMAN

    The entry is from https://medlineplus.gov/genetics/gene/edar

    References

    1. Arte S, Parmanen S, Pirinen S, Alaluusua S, Nieminen P. Candidate geneanalysis of tooth agenesis identifies novel mutations in six genes and suggestssignificant role for WNT and EDA signaling and allele combinations. PLoS One.2013 Aug 22;8(8):e73705. doi: 10.1371/journal.pone.0073705.
    2. Azeem Z, Naqvi SK, Ansar M, Wali A, Naveed AK, Ali G, Hassan MJ, Tariq M,Basit S, Ahmad W. Recurrent mutations in functionally-related EDA and EDAR genes underlie X-linked isolated hypodontia and autosomal recessive hypohidroticectodermal dysplasia. Arch Dermatol Res. 2009 Sep;301(8):625-9. doi:10.1007/s00403-009-0975-1.
    3. Bashyam MD, Chaudhary AK, Reddy EC, Reddy V, Acharya V, Nagarajaram HA, DeviAR, Bashyam L, Dalal AB, Gupta N, Kabra M, Agarwal M, Phadke SR, Tainwala R,Kumar R, Hariharan SV. A founder ectodysplasin A receptor (EDAR) mutation resultsin a high frequency of the autosomal recessive form of hypohidrotic ectodermaldysplasia in India. Br J Dermatol. 2012 Apr;166(4):819-29. doi:10.1111/j.1365-2133.2011.10707.x.
    4. Cluzeau C, Hadj-Rabia S, Jambou M, Mansour S, Guigue P, Masmoudi S, Bal E,Chassaing N, Vincent MC, Viot G, Clauss F, Manière MC, Toupenay S, Le Merrer M,Lyonnet S, Cormier-Daire V, Amiel J, Faivre L, de Prost Y, Munnich A, BonnefontJP, Bodemer C, Smahi A. Only four genes (EDA1, EDAR, EDARADD, and WNT10A) accountfor 90% of hypohidrotic/anhidrotic ectodermal dysplasia cases. Hum Mutat. 2011Jan;32(1):70-2. doi: 10.1002/humu.21384.
    5. Monreal AW, Ferguson BM, Headon DJ, Street SL, Overbeek PA, Zonana J.Mutations in the human homologue of mouse dl cause autosomal recessive anddominant hypohidrotic ectodermal dysplasia. Nat Genet. 1999 Aug;22(4):366-9.
    6. Naeem M, Muhammad D, Ahmad W. Novel mutations in the EDAR gene in twoPakistani consanguineous families with autosomal recessive hypohidroticectodermal dysplasia. Br J Dermatol. 2005 Jul;153(1):46-50.
    7. Wiśniewski SA, Kobielak A, Trzeciak WH, Kobielak K. Recent advances inunderstanding of the molecular basis of anhidrotic ectodermal dysplasia:discovery of a ligand, ectodysplasin A and its two receptors. J Appl Genet.2002;43(1):97-107. Review.
    8. Wohlfart S, Hammersen J, Schneider H. Mutational spectrum in 101 patients withhypohidrotic 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.
    9. Wright JT, Grange DK, Fete M. Hypohidrotic Ectodermal Dysplasia. 2003 Apr 28[updated 2017 Jun 1]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH,Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): Universityof Washington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK1112/
    10. Wu S, Tan J, Yang Y, Peng Q, Zhang M, Li J, Lu D, Liu Y, Lou H, Feng Q, Lu Y, Guan Y, Zhang Z, Jiao Y, Sabeti P, Krutmann J, Tang K, Jin L, Xu S, Wang S.Genome-wide scans reveal variants at EDAR predominantly affecting hairstraightness in Han Chinese and Uyghur populations. Hum Genet. 2016Nov;135(11):1279-1286.
    11. Zeng B, Zhao Q, Li S, Lu H, Lu J, Ma L, Zhao W, Yu D. Novel EDA or EDARMutations Identified in Patients with X-Linked Hypohidrotic Ectodermal Dysplasia or Non-Syndromic Tooth Agenesis. Genes (Basel). 2017 Oct 5;8(10). pii: E259. doi:10.3390/genes8100259.
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