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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9BQB6: Variant p.Arg98Trp

Vitamin K epoxide reductase complex subunit 1
Gene: VKORC1
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Variant information Variant position: help 98 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] 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: help From Arginine (R) to Tryptophan (W) at position 98 (R98W, p.Arg98Trp). 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: help 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: help -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
Variant description: help In VKCFD2; strongly reduced enzyme activity. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 98 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 163 The length of the canonical sequence.
Location on the sequence: help QSNSIFGCIFYTLQLLLGCL R TRWASVLMLLSSLVSLAGSV 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         QSNSIFGCIFYTLQLLLGCLRTRWASVLMLLSSLVSLAGSV

Mouse                         QSNSIFGCLFYTLQLLLGCLRGRWASILLVLSSLVSVAGSV

Rat                           QSNSIFGCMFYTIQLLLGCLRGRWASILLILSSLVSVAGSL

Bovine                        QSNSIFGCIFYTLQLLLGCLQGRWASVLLRLSCLVSLAGSV
Sequence annotation in neighborhood: help 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 1 – 163 Vitamin K epoxide reductase complex subunit 1
Topological domain 96 – 100 Cytoplasmic
Binding site 80 – 80
Alternative sequence 59 – 163 WGRGFGLVEHVLGQDSILNQSNSIFGCIFYTLQLLLGCLRTRWASVLMLLSSLVSLAGSVYLAWILFFVLYDFCIVCITTYAINVSLMWLSFRKVQEPQGKAKRH -> LPADTLGLCPDAAELPGVSRWFCLPGLDPVLRAL. In isoform 3.
Alternative sequence 95 – 163 GCLRTRWASVLMLLSSLVSLAGSVYLAWILFFVLYDFCIVCITTYAINVSLMWLSFRKVQEPQGKAKRH -> DGVSPCCPGWSQAICLPQPPKVLGGLQALPADTLGLCPDAAELPGVSRWFCLPGLDPVLRAL. In isoform 2.
Mutagenesis 80 – 80 N -> A. Decreased vitamin K epoxide reductase activity.
Mutagenesis 85 – 85 C -> A. Reduces enzyme activity by about 25%.
Mutagenesis 85 – 85 C -> S. Reduces enzyme activity by about 75%.
Mutagenesis 96 – 96 C -> AS. Reduces enzyme activity by about 70%.
Mutagenesis 98 – 98 R -> DE. Reduces enzyme activity by about 80%. Decreases inhibition by warfarin.
Mutagenesis 98 – 98 R -> K. No effect on enzyme activity. Decreases inhibition by warfarin.



Literature citations
Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2.
Rost S.; Fregin A.; Ivaskevicius V.; Conzelmann E.; Hoertnagel K.; Pelz H.-J.; Lappegard K.; Seifried E.; Scharrer I.; Tuddenham E.G.D.; Mueller C.R.; Strom T.M.; Oldenburg J.;
Nature 427:537-541(2004)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); FUNCTION; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; VARIANTS CMRES LEU-29; ALA-45; GLY-58 AND ARG-128; VARIANT VKCFD2 TRP-98; Site-directed mutagenesis of coumarin-type anticoagulant-sensitive VKORC1: evidence that highly conserved amino acids define structural requirements for enzymatic activity and inhibition by warfarin.
Rost S.; Fregin A.; Hunerberg M.; Bevans C.G.; Muller C.R.; Oldenburg J.;
Thromb. Haemost. 94:780-786(2005)
Cited for: FUNCTION; POTENTIAL REDOX-ACTIVE SITE; CATALYTIC ACTIVITY; ACTIVITY REGULATION; SUBCELLULAR LOCATION; MUTAGENESIS OF CYS-16; CYS-43; CYS-51; SER-57; CYS-85; CYS-96; ARG-98; CYS-132; CYS-135 AND TYR-139; CHARACTERIZATION OF VARIANT VKCFD2 TRP-98;
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.