Bioinformatics Database
EDA: Ectodysplasin A
Cellular Process
Tooth Eruption
Gene Name
EDA: Ectodysplasin A
Gene ID
1896
Gene Sequence
General Description
The protein encoded by this gene is a type II membrane protein that can be cleaved by furin to produce a secreted form. The encoded protein, which belongs to the tumor necrosis factor family, acts as a homotrimer and may be involved in cell-cell signaling during the development of ectodermal organs. Defects in this gene are a cause of ectodermal dysplasia, anhidrotic, which is also known as X-linked hypohidrotic ectodermal dysplasia.
Alternative titles; symbols
ECTODYSPLASIN EDA1 GENE ED1 GENE; ED1
Chromosome
Chromosome X
Cytogenetic location
Xq13.1
Encoded Protein
Ectodysplasin-A isoform 1
Function of the protein in oral and tooth development
Pillas et al., (2010) performed a genome-wide association study of time to first tooth eruption. The results identified 5 loci and several genes with links to tooth and other organ development including EDA and IGF2BP1.
Fatemifar et al.,(2013) conducted genome-wide association study and reported association of six loci with primary tooth eruption including KCNJ2/KCNJ16, IGF2BP1, and EDA.
Dental and Oral Diseases
Ectodermal dysplasia 1, hypohidrotic, X-linked
(OMIM ID: 305100)
Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings.
Tooth agenesis, selective, X-linked 1
(OMIM ID: 313500)
Selective tooth agenesis is a congenital disorder divided into two types based on the number of missing teeth, i.e. hypodontia which is the absence of <6 teeth, and oligodontia which is agenesis of >6 permanent teeth excluding the third molars (Aslam et al., 2020).
Protein Sequence
>NP_001390.1 ectodysplasin-A isoform 1 [Homo sapiens]
MGYPEVERRELLPAAAPRERGSQGCGCGGAPARAGEGNSCLLFLGFFGLSLALHLLTLCCYLELRSELRR
ERGAESRLGGSGTPGTSGTLSSLGGLDPDSPITSHLGQPSPKQQPLEPGEAALHSDSQDGHQMALLNFFF
PDEKPYSEEESRRVRRNKRSKSNEGADGPVKNKKKGKKAGPPGPNGPPGPPGPPGPQGPPGIPGIPGIPG
TTVMGPPGPPGPPGPQGPPGLQGPSGAADKAGTRENQPAVVHLQGQGSAIQVKNDLSGGVLNDWSRITMN
PKVFKLHPRSGELEVLVDGTYFIYSQVEVYYINFTDFASYEVVVDEKPFLQCTRSIETGKTNYNTCYTAG
VCLLKARQKIAVKMVHADISINMSKHTTFFGAIRLGEAPAS
Mutations
Ectodermal dysplasia 1, hypohidrotic, X-linked (Selected Mutations, visit OMIM 300451 for details)
TYR61HIS: Kere et al. (1996) identified a tyr61-to-his mutation in a novel transmembrane protein resulting from a T-to-C transition at nucleotide 423. This was 1 of 9 point mutations identified in patients with this disorder.
ARG69LEU: Kere et al. (1996) found an association between EDA and a point mutation, a G-to-T transversion at nucleotide 448 resulting in an arg69-to-leu amino acid substitution.
GLN23TER: Mutations found by Ferguson et al. (1998) in patients with XHED was a 366C-T transition resulting in a gln23-to-ter nonsense mutation.
GLU63LYS: Mutations found by Ferguson et al. (1998) in patients with XHED was a 429G-A transition resulting in a glu63-to-lys amino acid substitution.
ARG155CYS: In a patient with XHED, Monreal et al. (1998) found a 704C-T transition in exon 3 of the EDA gene, causing an arg155-to-cys amino acid substitution in isoform II of the EDA protein.
ARG156CYS: Monreal et al. (1998) found a 707C-T transition in exon 3 of the EDA gene, predicted to result in an arg156-to-cys amino acid substitution in isoform II of the EDA protein. This was a de novo mutation
ARG156HIS: Monreal et al. (1998) found a 708G-A transition in exon 3 of the EDA gene, resulting in an arg156-to-his amino acid substitution in isoform II of the EDA protein.
PRO209LEU: Monreal et al. (1998) found an 867C-T transition in exon 5, predicted to result in a pro209-to-leu amino acid substitution in isoform II of the EDA protein.
GLY224ALA : Monreal et al. (1998) found a 912G-C transversion in exon 5 of the EDA gene, predicted to result in a gly224-to-ala amino acid substitution in isoform II of the EDA protein.
ALA349THR: n 2 apparently unrelated families, Monreal et al. (1998) found that males with XHED had a 1285G-A transition in exon 9 of the EDA gene, predicted to result in an ala349-to-thr amino acid substitution in isoform II of the EDA protein.
Tooth agenesis, selective, X-linked 1 (Selected Mutations, visit OMIM 300451 for details)
ARG65GLY: Tao et al. (2006) identified a 193C-G transversion in exon 1 of the EDA gene, resulting in an arg65-to-gly (R65G) substitution in the juxtamembrane region of the protein, in all affected males and carrier females.
GLN358GLU: Tarpey et al. (2007) identified a 1072C-G transversion in exon 8 of the EDA gene, resulting in a gln358-to-glu (Q358E) substitution.
THR338MET: Han et al. (2008) identified a hemizygous 1013C-T transition in exon 8 of the EDA gene, resulting in a thr338-to-met (T338M) substitution that changes the residue from hydrophilic to hydrophobic and is predicted to cause a conformational change affecting the stability of the homotrimer.
Related Literature
Fatemifar et al.,(2013). https://doi.org/10.1093/hmg/ddt231
Pillas et al., (2010). https://doi.org/10.1371/journal.pgen.1000856
Aslam et al., (2020). https://doi.org/10.5455/JPMA.42628
Ferguson et al. (1998). https://doi.org/10.1136/jmg.35.2.112
Kere et al. (1996). https://doi.org/10.1038/ng0895-409
Monreal et al., (1998). https://doi.org/10.1086/301984
Han et al., (2008). https://doi.org/10.1016/j.ejmg.2008.06.002
Tarpey et al., (2007). https://doi.org/10.1002/ajmg.a.31567
Tao et al., (2006). https://doi.org/10.1007/s10038-006-0389-2
