UniProtKB/SwissProt variant VAR

Variant information

Variant position:

193

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 Tryptophan (W) at position 193 (R193W, p.Arg193Trp).

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 large size and aromatic (W)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-3

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:

Thrombotic thrombocytopenic purpura congenital (TTP) [MIM:274150]: A hematologic disease characterized by hemolytic anemia with fragmentation of erythrocytes, thrombocytopenia, diffuse and non-focal neurologic findings, decreased renal function and fever. Recessive. {ECO:0000269|PubMed:11586351, ECO:0000269|PubMed:12181489, ECO:0000269|PubMed:12393505, ECO:0000269|PubMed:12614216, ECO:0000269|PubMed:12753286, ECO:0000269|PubMed:14512317, ECO:0000269|PubMed:14563640, ECO:0000269|PubMed:15009458, ECO:0000269|PubMed:15126318, ECO:0000269|PubMed:15327386, ECO:0000269|PubMed:16160007, ECO:0000269|PubMed:16449289, ECO:0000269|PubMed:16453338, ECO:0000269|PubMed:16796708, ECO:0000269|PubMed:16807643, ECO:0000269|PubMed:17003922, ECO:0000269|PubMed:18443791, ECO:0000269|PubMed:19055667, ECO:0000269|PubMed:19116307, ECO:0000269|PubMed:22075512}. 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 TTP; low activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs281875287 [ dbSNP | Ensembl ]

Sequence information

Variant position:

193

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:

DLVLYITRFDLELPDGNRQV R GVTQLGGACSPTWSCLITED

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                         DLVLYITRFDLELPDGNRQVRGVTQLGGACSPTWSCLITED

Mouse                         DLILYITRFDLELPDGNQQVRGVTQLGGACSLSWSCLITED

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	75 – 1427	A disintegrin and metalloproteinase with thrombospondin motifs 13
Domain	80 – 286	Peptidase M12B
Metal binding	173 – 173	Calcium
Metal binding	182 – 182	Calcium; high affinity
Metal binding	184 – 184	Calcium; high affinity
Metal binding	187 – 187	Calcium; high affinity
Metal binding	212 – 212	Calcium; high affinity
Disulfide bond	155 – 208
Alternative sequence	2 – 329	Missing. In isoform 4.
Mutagenesis	173 – 173	D -> A. No change in calcium dependence for proteolysis.
Mutagenesis	184 – 184	E -> A. Dramatically reduced affinity for calcium.
Mutagenesis	187 – 187	D -> A. Dramatically reduced affinity for calcium.
Mutagenesis	212 – 212	E -> A. Dramatically reduced affinity for calcium.

Literature citations

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;

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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q76LX8: Variant p.Arg193Trp