UniProtKB/SwissProt variant VAR

Vitamin K epoxide reductase complex subunit 1
Gene: VKORC1
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Variant information Variant position:

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

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:

From Leucine (L) to Arginine (R) at position 128 (L128R, p.Leu128Arg). 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 hydrophobic (L) to large size and basic (R) 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
Variant description:

In CMRES. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs104894542 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

LSSLVSLAGSVYLAWILFFV L YDFCIVCITTYAINVSLMWL 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                         LSSLVSLAGSVYLAWILFFVLYDFCIVCITTYAINVSLMWL

Mouse                         LSSLVSVAGSVYLAWILFFVLYDFCIVCITTYAINVGLMLL

Rat                           LSSLVSVAGSLYLAWILFFVLYDFCIVCITTYAINAGLMLL

Bovine                        LSCLVSLAGSVYLAWILFFVLYDFCIVCITTYAINVGLTVL

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	1 – 163	Vitamin K epoxide reductase complex subunit 1
Transmembrane	101 – 128	Helical
Binding site	135 – 135
Binding site	139 – 139
Binding site	139 – 139
Alternative sequence	59 – 163	WGRGFGLVEHVLGQDSILNQSNSIFGCIFYTLQLLLGCLRTRWASVLMLLSSLVSLAGSVYLAWILFFVLYDFCIVCITTYAINVSLMWLSFRKVQEPQGKAKRH -> LPADTLGLCPDAAELPGVSRWFCLPGLDPVLRAL. In isoform 3.
Alternative sequence	95 – 163	GCLRTRWASVLMLLSSLVSLAGSVYLAWILFFVLYDFCIVCITTYAINVSLMWLSFRKVQEPQGKAKRH -> DGVSPCCPGWSQAICLPQPPKVLGGLQALPADTLGLCPDAAELPGVSRWFCLPGLDPVLRAL. In isoform 2.
Mutagenesis	120 – 120	L -> Q. Decreases enzyme activity moderately. Decreases inhibition by warfarin.
Mutagenesis	128 – 128	L -> QS. Decreases enzyme activity by about 80%. Decreases inhibition by warfarin.
Mutagenesis	132 – 132	C -> S. Nearly abolishes enzyme activity.
Mutagenesis	135 – 135	C -> S. Nearly abolishes enzyme activity.
Mutagenesis	139 – 139	Y -> A. Decreased vitamin K epoxide reductase activity.
Mutagenesis	139 – 139	Y -> CGS. Decreases enzyme activity moderately. Strongly decreases inhibition by warfarin.
Mutagenesis	139 – 139	Y -> F. No effect on enzyme activity. Strongly 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;

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.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9BQB6: Variant p.Leu128Arg