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UniProtKB/Swiss-Prot P37023: Variant p.Glu407Asp

Serine/threonine-protein kinase receptor R3
Gene: ACVRL1
Chromosomal location: 12q11-q14
Variant information

Variant position:  407
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 Glutamate (E) to Aspartate (D) at position 407 (E407D, p.Glu407Asp).
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:  Similar physico-chemical property. Both residues are medium size and acidic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  2
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:  Telangiectasia, hereditary hemorrhagic, 2 (HHT2) [MIM:600376]: A multisystemic vascular dysplasia leading to dilation of permanent blood vessels and arteriovenous malformations of skin, mucosa, and viscera. The disease is characterized by recurrent epistaxis and gastro-intestinal hemorrhage. Visceral involvement includes arteriovenous malformations of the lung, liver, and brain. {ECO:0000269|PubMed:10694922, ECO:0000269|PubMed:10767348, ECO:0000269|PubMed:11170071, ECO:0000269|PubMed:11484689, ECO:0000269|PubMed:14684682, ECO:0000269|PubMed:15024723, ECO:0000269|PubMed:15712270, ECO:0000269|PubMed:16525724, ECO:0000269|PubMed:16752392, ECO:0000269|PubMed:20414677, ECO:0000269|PubMed:26176610, ECO:0000269|PubMed:8640225, ECO:0000269|PubMed:9245985}. 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 HHT2.
Any additional useful information about the variant.



Sequence information

Variant position:  407
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  503
The length of the canonical sequence.

Location on the sequence:   TDCFESYKWTDIWAFGLVLW  E IARRTIVNGIVEDYRPPFYD
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                         TDCFESYKWTDIWAFGLVLWEIARRTIVNGIVEDYRPPFYD

Mouse                         TDCFESYKWTDIWAFGLVLWEIARRTIINGIVEDYRPPFYD

Rat                           TDCFESYKWTDIWAFGLVLWEIARRTIINGIVEDYRPPFYD

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 22 – 503 Serine/threonine-protein kinase receptor R3
Topological domain 142 – 503 Cytoplasmic
Domain 202 – 492 Protein kinase
Helix 390 – 410


Literature citations

Analysis of ALK-1 and endoglin in newborns from families with hereditary hemorrhagic telangiectasia type 2.
Abdalla S.A.; Pece-Barbara N.; Vera S.; Tapia E.; Paez E.; Bernabeu C.; Letarte M.;
Hum. Mol. Genet. 9:1227-1237(2000)
Cited for: VARIANTS HHT2 GLY-48-49-ALA DELINS EP; CYS-50; SER-232 DEL; ILE-333; TYR-344 AND ASP-407;

Hepatic manifestation is associated with ALK1 in hereditary hemorrhagic telangiectasia: identification of five novel ALK1 and one novel ENG mutations.
Kuehl H.K.A.; Caselitz M.; Hasenkamp S.; Wagner S.; El-Harith E.-H.A.; Manns M.P.; Stuhrmann M.;
Hum. Mutat. 25:320-320(2005)
Cited for: VARIANTS HHT2 TRP-67; TRP-374; LYS-379; ASP-407; TRP-411; VAL-425 AND PHE-425 DEL;

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.