UniProtKB/Swiss-Prot P07204: Variant p.Ala473Val

Thrombomodulin
Gene: THBD
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Variant information Variant position:

473 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Alanine (A) to Valine (V) at position 473 (A473V, p.Ala473Val). 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 small size and hydrophobic (A) to medium size and hydrophobic (V) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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
Other resources:

Links to websites of interest for the variant.

Variant rs1042579 [ dbSNP | Ensembl ]

Sequence information Variant position:

473 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

575 The length of the canonical sequence.
Location on the sequence:

GVCHNLPGTFECICGPDSAL A RHIGTDCDSGKVDGGDSGSG 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                         GVCHNLPGTFECICGPDSALARHIGTDCDSGKVD---GGDSGSG

                              EACRNLPGTYECICGPDSPLAGQVATDCGRIISDPDGDSDS

Mouse                         SECRNFPGSYECICGPDTALAGQISKDCDPIPVREDTKEEE

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.

Type	Positions	Description
Chain	19 – 575	Thrombomodulin
Topological domain	19 – 515	Extracellular
Domain	441 – 481	EGF-like 6; calcium-binding
Glycosylation	490 – 490	O-linked (Xyl...) (chondroitin sulfate) serine
Glycosylation	492 – 492	O-linked (Xyl...) (chondroitin sulfate) serine
Disulfide bond	466 – 480
Mutagenesis	490 – 490	S -> E. Improved overall glycosaminoglycan attachment, likely due to improved xylosyltransferase acceptor consensus sequence around Ser-492.
Mutagenesis	492 – 492	S -> G. Reduced glycosaminoglycan attachment.
Beta strand	473 – 477

Literature citations
Submission
SeattleSNPs variation discovery resource;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANT VAL-473; The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
The MGC Project Team;
Genome Res. 14:2121-2127(2004)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]; VARIANT VAL-473; A common thrombomodulin amino acid dimorphism is associated with myocardial infarction.
Norlund L.; Holm J.; Zoller B.; Oehlin A.-K.;
Thromb. Haemost. 77:248-251(1997)
Cited for: VARIANT VAL-473; Thrombomodulin Ala455Val polymorphism and risk of coronary heart disease.
Wu K.K.; Aleksic N.; Ahn C.; Boerwinkle E.; Folsom A.R.; Juneja H.;
Circulation 103:1386-1389(2001)
Cited for: VARIANT VAL-473; Mutations in the thrombomodulin gene are rare in patients with severe thrombophilia.
Faioni E.M.; Franchi F.; Castaman G.; Biguzzi E.; Rodeghiero F.;
Br. J. Haematol. 118:595-599(2002)
Cited for: VARIANT THPH12 TYR-486; VARIANT VAL-473; Thrombomodulin mutations in atypical hemolytic-uremic syndrome.
Delvaeye M.; Noris M.; De Vriese A.; Esmon C.T.; Esmon N.L.; Ferrell G.; Del-Favero J.; Plaisance S.; Claes B.; Lambrechts D.; Zoja C.; Remuzzi G.; Conway E.M.;
N. Engl. J. Med. 361:345-357(2009)
Cited for: VARIANTS AHUS6 THR-43; GLY-53; LEU-81; TYR-486; SER-495 AND LEU-501; CHARACTERIZATION OF VARIANTS AHUS6 THR-43; GLY-53; LEU-81; TYR-486; SER-495 AND LEU-501; VARIANT VAL-473;

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.