EDAR V370A - GET-Evidence

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EDAR V370A

(EDAR Val370Ala)


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Short summary

Associated with thicker hair, common in Chinese and Japanese individuals and thought to be Asian-specific.

Variant evidence
Computational 1

Other variants in this gene are associated with effect on hair thickness. Polyphen gives possible functional effect.

Functional 1

Lower activity of NF-kappaB.

See Fujimoto A et al. 2008 (18065779).

Case/Control 4

See Fujimoto A et al. 2008 (18065779).

Familial

No familial information.

 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Low clinical importance, Likely benign

(The "low clinical importance, likely" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • G @ chr2:109513601: 1.1% (114/10758) in EVS
  • G @ chr2:108880032: 12.5% (16/128) in GET-Evidence
  • Frequency shown in summary reports: 1.1% (114/10758)

Publications
 

Fujimoto A, Kimura R, Ohashi J, Omi K, Yuliwulandari R, Batubara L, Mustofa MS, Samakkarn U, Settheetham-Ishida W, Ishida T, Morishita Y, Furusawa T, Nakazawa M, Ohtsuka R, Tokunaga K. A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness. Hum Mol Genet. 2008 Mar 15;17(6):835-43. Epub 2007 Dec 8. PubMed PMID: 18065779.

C allele (Ala) is associated with larger cross-sectional area in Indonesian sample (p = 5.5 * 10^-3) and Thai-Mai sample (9.5 * 10^-4).

Functional analysis examining the interaction between EDAR and the EDAR-binding death domain adapter protein, EDARADD, which results in activation of NF-kappaB. The C allele showed lower NF-kappaB induced activation of a luciferase reporter, indicating this variant causes lower activity of NF-kappaB.

Mou C, Thomason HA, Willan PM, Clowes C, Harris WE, Drew CF, Dixon J, Dixon MJ, Headon DJ. Enhanced ectodysplasin-A receptor (EDAR) signaling alters multiple fiber characteristics to produce the East Asian hair form. Hum Mutat. 2008 Dec;29(12):1405-11. PubMed PMID: 18561327.

 

Fujimoto A, Ohashi J, Nishida N, Miyagawa T, Morishita Y, Tsunoda T, Kimura R, Tokunaga K. A replication study confirmed the EDAR gene to be a major contributor to population differentiation regarding head hair thickness in Asia. Hum Genet. 2008 Sep;124(2):179-85. Epub 2008 Aug 13. PubMed PMID: 18704500.

 

Kimura R, Yamaguchi T, Takeda M, Kondo O, Toma T, Haneji K, Hanihara T, Matsukusa H, Kawamura S, Maki K, Osawa M, Ishida H, Oota H. A common variation in EDAR is a genetic determinant of shovel-shaped incisors. Am J Hum Genet. 2009 Oct;85(4):528-35. PubMed PMID: 19804850; PubMed Central PMCID: PMC2756549.

 

Genomes
 

huC30901 - CGI sample GS00253-DNA_B01_200_37
het G @ chr2:109513601

 

GS18526 - var-GS18526-1100-36-ASM
hom G @ chr2:108880033

 

GS18537 - var-GS18537-1100-36-ASM
hom G @ chr2:108880033

 

Added in this revision:

GS18555 - var-GS18555-1100-36-ASM
hom G @ chr2:108880033

 

NA18555

 

NA18956

 

snp-1

 

snp-2

 

snp-3

 

Other external references
 

    dbSNP
  • rs3827760
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.485 (possibly damaging)
    Web search results (17 hits -- see all)
  • Positive Selection in East Asians for an EDAR Allele that ...
    Positive Selection in East Asians for an EDAR Allele that Enhances NF-κB Activation ... V370A is located in the death domain, a protein interaction module, of EDAR. ...
    www.ncbi.nlm.nih.gov/pmc/articles/PMC2374902
  • PLoS ONE: Positive Selection in East Asians for an EDAR ...
    PLoS ONE: an inclusive, peer-reviewed, open-access resource from the PUBLIC LIBRARY OF SCIENCE. ... V370A is located in the death domain, a protein interaction module, of EDAR. ...
    plosone.org/article/info:doi/10.1371/journal.pone.0002209
  • Figure 2 : Genome-wide detection and characterization of ...
    FIGURE 2. Global distribution of SLC24A5 A111T and EDAR V370A. ... b, EDAR V370A is common in Asia and the Americas, but absent in Europe and Africa. Next figure | Previous ...
    nature.com/nature/journal/.../fig_tab/nature06250_F2.html
  • Figures and Tables : Genome-wide detection and ...
    Nature is the international weekly journal of science: a magazine style journal that publishes full-length research papers in all disciplines of science, as well as ...
    nature.com/nature/journal/.../fig_tab/nature06250_ft.html
  • untitled
    A mutation encoding a V370A substi- tution in EDAR is near fixation in Asia and absent in ... V370A is common in Asia and the Americas, but absent in Europe and ...
    dceg.cancer.gov/files/genomicscourse/sabeti-102007.pdf
  • OMIM: 604095
    By embryonic days 16 and 17, EDAR was expressed in large amounts in the maturing follicles. ... the EDAR gene, resulting in a val370-to-ala (V370A) substitution in ...
    www.genome.jp/dbget-bin/www_bget?omim+604095
  • USACO 日本人論文紹介 2009年9月-12月
    Ectodysplasin A receptor (EDAR )は、歯、毛髪、汗腺など外胚葉由来器官の発生に関わる遺伝子であり、近年、非同義多型であるEDAR T1540C(V370A)が毛髪の太さと関連することが示された。 また、1540Cの分布は、モンゴロイド特有の形態形質であるシャベル型切歯の分布ともよく一致する。 ...
    www.usaco.co.jp/article/past.html
  • Type III 95%
    Gene name SWISS-PROT ID Variant site Phosphorylation site SWISS-PROT ... gruop(s) Added kinase family(s) Removed kinase gruop(s) Removed kinase family(s) ...
    www.nih.go.kr/phosphovariant/html/group_whole/TypeIII_95.txt

Other in silico analyses
 

  • NBLOSUM100 score = 2
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

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