Home  |  Contact

UniProtKB/Swiss-Prot Q9UNE0: Variant p.Arg420Gln

Tumor necrosis factor receptor superfamily member EDAR
Gene: EDAR
Chromosomal location: 2q11-q13
Variant information

Variant position:  420
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Arginine (R) to Glutamine (Q) at position 420 (R420Q, p.Arg420Gln).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from large size and basic (R) to medium size and polar (Q)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in disease:  Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant (ECTD10A) [MIM:129490]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. It is an autosomal dominant condition characterized by hypotrichosis, abnormal or missing teeth, and hypohidrosis due to the absence of sweat glands. {ECO:0000269|PubMed:10431241, ECO:0000269|PubMed:18231121}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Involvement in disease:  Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive (ECTD10B) [MIM:224900]: A disorder due to abnormal development of two or more ectodermal structures, and characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands. {ECO:0000269|PubMed:10431241, ECO:0000269|PubMed:15373768, ECO:0000269|PubMed:16029325, ECO:0000269|PubMed:16435307, ECO:0000269|PubMed:18231121, ECO:0000269|PubMed:19438931, ECO:0000269|PubMed:20979233, ECO:0000269|PubMed:27657131}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In ECTD10A and ECTD10B; abolishes NF-kappa-B activation and reduces JNK activation.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  420
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  448
The length of the canonical sequence.

Location on the sequence:   RISTAGYSIPELLTKLVQIE  R LDAVESLCADILEWAGVVPP
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         RISTAGYSIPELLTKLVQIERLDAVESLCADILEWAGVVPP

Mouse                         RISTAGYSIPELLTKLVQIERLDAVESLCADILEWAGVVPP

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 27 – 448 Tumor necrosis factor receptor superfamily member EDAR
Topological domain 209 – 448 Cytoplasmic
Domain 358 – 431 Death


Literature citations

Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia.
Monreal A.W.; Ferguson B.M.; Headon D.J.; Street S.L.; Overbeek P.A.; Zonana J.;
Nat. Genet. 22:366-369(1999)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1); VARIANTS ECTD10B ARG-87 AND HIS-89; VARIANT ECTD10A GLN-420;

The ectodermal dysplasia receptor activates the nuclear factor-kappaB, JNK, and cell death pathways and binds to ectodysplasin A.
Kumar A.; Eby M.T.; Sinha S.; Jasmin A.; Chaudhary P.M.;
J. Biol. Chem. 276:2668-2677(2001)
Cited for: CHARACTERIZATION OF VARIANT GLN-420; MUTAGENESIS OF GLU-379; CHARACTERIZATION; INTERACTION WITH TRAF1 AND TRAF3;

Mutations in EDAR account for one-quarter of non-ED1-related hypohidrotic ectodermal dysplasia.
Chassaing N.; Bourthoumieu S.; Cossee M.; Calvas P.; Vincent M.-C.;
Hum. Mutat. 27:255-259(2006)
Cited for: VARIANTS ECTD10B TYR-47; HIS-89; ALA-110; ARG-148; PHE-377; MET-403; PRO-413; THR-418; GLN-420 AND CYS-434;

Mutation screening of the ectodysplasin-A receptor gene EDAR in hypohidrotic ectodermal dysplasia.
van der Hout A.H.; Oudesluijs G.G.; Venema A.; Verheij J.B.G.M.; Mol B.G.J.; Rump P.; Brunner H.G.; Vos Y.J.; van Essen A.J.;
Eur. J. Hum. Genet. 16:673-679(2008)
Cited for: VARIANTS ECTD10B HIS-89 AND ALA-110; VARIANT ECTD10A GLN-420;

Only four genes (EDA1, EDAR, EDARADD, and WNT10A) account for 90% of hypohidrotic/anhidrotic ectodermal dysplasia cases.
Cluzeau C.; Hadj-Rabia S.; Jambou M.; Mansour S.; Guigue P.; Masmoudi S.; Bal E.; Chassaing N.; Vincent M.C.; Viot G.; Clauss F.; Maniere M.C.; Toupenay S.; Le Merrer M.; Lyonnet S.; Cormier-Daire V.; Amiel J.; Faivre L.; de Prost Y.; Munnich A.; Bonnefont J.P.; Bodemer C.; Smahi A.;
Hum. Mutat. 32:70-72(2011)
Cited for: VARIANTS ECTD10B HIS-89; GLN-358; GLN-396 INS; MET-403; PHE-408 AND GLN-420;

Eight mutations of three genes (EDA, EDAR, and WNT10A) identified in seven hypohidrotic ectodermal dysplasia patients.
Zeng B.; Xiao X.; Li S.; Lu H.; Lu J.; Zhu L.; Yu D.; Zhao W.;
Genes (Basel) 7:0-0(2016)
Cited for: VARIANT ECTD10B GLN-420; VARIANT LEU-370;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.