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UniProtKB/Swiss-Prot Q76LX8: Variant p.Gln448Glu

A disintegrin and metalloproteinase with thrombospondin motifs 13
Gene: ADAMTS13
Variant information

Variant position:  448
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 Glutamine (Q) to Glutamate (E) at position 448 (Q448E, p.Gln448Glu).
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 medium size and polar (Q) to medium size and acidic (E)
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

Polymorphism:  Genetic variations in ADAMTS13 coding region influence plasmatic ADAMTS13 activity levels. Dependent on the sequence context, the same polymorphisms might be either positive or negative modifiers of gene expression, thereby altering the phenotype of ADAMTS13 deficiency.
Additional information on the polymorphism described.

Variant description:  Does not affect protein secretion; normal proteolytic activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  448
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1427
The length of the canonical sequence.

Location on the sequence:   LQAEMCNTQACEKTQLEFMS  Q QCARTDGQPLRSSPGGASFY
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                         LQAEMCNTQACEKTQLEFMSQQCARTDGQPLRSSPGGASFY

Mouse                         LQAKMCNTQACEKTQLEFMSEQCAQTDRQPLQLSQGTASFY

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 75 – 1427 A disintegrin and metalloproteinase with thrombospondin motifs 13
Region 440 – 556 Cysteine-rich
Helix 442 – 451


Literature citations

Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura.
Levy G.G.; Nichols W.C.; Lian E.C.; Foroud T.; McClintick J.N.; McGee B.M.; Yang A.Y.; Siemieniak D.R.; Stark K.R.; Gruppo R.; Sarode R.; Shurin S.B.; Chandrasekaran V.; Stabler S.P.; Sabio H.; Bouhassira E.E.; Upshaw J.D. Jr.; Ginsburg D.; Tsai H.-M.;
Nature 413:488-494(2001)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); INVOLVEMENT IN THROMBOTIC THROMBOCYTOPENIC PURPURA; VARIANTS TTP ASP-96; CYS-102; ILE-196; HIS-398; GLY-528; CYS-692; GLY-951; GLY-1024 AND TYR-1213; VARIANTS TRP-7; GLU-448; ALA-618; HIS-625; VAL-732; VAL-900 AND THR-1033;

Submission
SeattleSNPs variation discovery resource;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS TRP-7; GLU-448; HIS-456; LEU-457; ALA-618; HIS-625; LYS-740; VAL-900; ARG-982; THR-1033 AND ILE-1226;

The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.
Clark H.F.; Gurney A.L.; Abaya E.; Baker K.; Baldwin D.T.; Brush J.; Chen J.; Chow B.; Chui C.; Crowley C.; Currell B.; Deuel B.; Dowd P.; Eaton D.; Foster J.S.; Grimaldi C.; Gu Q.; Hass P.E.; Heldens S.; Huang A.; Kim H.S.; Klimowski L.; Jin Y.; Johnson S.; Lee J.; Lewis L.; Liao D.; Mark M.R.; Robbie E.; Sanchez C.; Schoenfeld J.; Seshagiri S.; Simmons L.; Singh J.; Smith V.; Stinson J.; Vagts A.; Vandlen R.L.; Watanabe C.; Wieand D.; Woods K.; Xie M.-H.; Yansura D.G.; Yi S.; Yu G.; Yuan J.; Zhang M.; Zhang Z.; Goddard A.D.; Wood W.I.; Godowski P.J.; Gray A.M.;
Genome Res. 13:2265-2270(2003)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 275-1427; VARIANT GLU-448;

Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity.
Kokame K.; Matsumoto M.; Soejima K.; Yagi H.; Ishizashi H.; Funato M.; Tamai H.; Konno M.; Kamide K.; Kawano Y.; Miyata T.; Fujimura Y.;
Proc. Natl. Acad. Sci. U.S.A. 99:11902-11907(2002)
Cited for: VARIANTS TTP PRO-268 AND TYR-508; VARIANTS GLU-448 AND SER-475; CHARACTERIZATION OF VARIANTS TTP PRO-268 AND TYR-508; CHARACTERIZATION OF VARIANTS GLU-448 AND SER-475;

Congenital thrombotic thrombocytopenic purpura in association with a mutation in the second CUB domain of ADAMTS13.
Pimanda J.E.; Maekawa A.; Wind T.; Paxton J.; Chesterman C.N.; Hogg P.J.;
Blood 103:627-629(2004)
Cited for: VARIANT TTP ILE-196; VARIANT GLU-448;

Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome.
Matsumoto M.; Kokame K.; Soejima K.; Miura M.; Hayashi S.; Fujii Y.; Iwai A.; Ito E.; Tsuji Y.; Takeda-Shitaka M.; Iwadate M.; Umeyama H.; Yagi H.; Ishizashi H.; Banno F.; Nakagaki T.; Miyata T.; Fujimura Y.;
Blood 103:1305-1310(2004)
Cited for: VARIANTS TTP TRP-193; PHE-673; TYR-908 AND CYS-1123; VARIANT GLU-448; CHARACTERIZATION OF VARIANTS TTP TRP-193; PHE-673; TYR-908 AND CYS-1123;

Modulation of ADAMTS13 secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation.
Plaimauer B.; Fuhrmann J.; Mohr G.; Wernhart W.; Bruno K.; Ferrari S.; Konetschny C.; Antoine G.; Rieger M.; Scheiflinger F.;
Blood 107:118-125(2006)
Cited for: CHARACTERIZATION OF VARIANTS TRP-7; GLU-448; ALA-618 AND VAL-732; CHARACTERIZATION OF VARIANT TTP TRP-1336; DISCUSSION OF MUTUAL MODULATORY EFFECTS OF POLYMORPHISMS;

In-vitro and in-vivo consequences of mutations in the von Willebrand factor cleaving protease ADAMTS13 in thrombotic thrombocytopenic purpura.
Donadelli R.; Banterla F.; Galbusera M.; Capoferri C.; Bucchioni S.; Gastoldi S.; Nosari S.; Monteferrante G.; Ruggeri Z.M.; Bresin E.; Scheiflinger F.; Rossi E.; Martinez C.; Coppo R.; Remuzzi G.; Noris M.;
Thromb. Haemost. 96:454-464(2006)
Cited for: VARIANTS TTP TRP-1060; CYS-1123 AND TRP-1219; CHARACTERIZATION OF VARIANTS TTP TRP-1060; CYS-1123 AND TRP-1219; VARIANT GLU-448;

Pregnancy-induced thrombocytopenia and TTP, and the risk of fetal death, in Upshaw-Schulman syndrome: a series of 15 pregnancies in 9 genotyped patients.
Fujimura Y.; Matsumoto M.; Kokame K.; Isonishi A.; Soejima K.; Akiyama N.; Tomiyama J.; Natori K.; Kuranishi Y.; Imamura Y.; Inoue N.; Higasa S.; Seike M.; Kozuka T.; Hara M.; Wada H.; Murata M.; Ikeda Y.; Miyata T.; George J.N.;
Br. J. Haematol. 144:742-754(2009)
Cited for: VARIANTS TTP THR-178; TRP-193; CYS-304; CYS-349; ASP-525 AND PRO-606; VARIANTS ARG-339; GLU-448 AND ALA-618;

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.