VKORC1

Summary

VKORC1 (vitamin K epoxide reductase complex subunit 1, HGNC:23663) is a protein-coding gene on chromosome 16p11.2, encoding Vitamin K epoxide reductase complex subunit 1 (Q9BQB6). Involved in vitamin K metabolism.

This gene encodes the catalytic subunit of the vitamin K epoxide reductase complex, which is responsible for the reduction of inactive vitamin K 2,3-epoxide to active vitamin K in the endoplasmic reticulum membrane. Vitamin K is a required co-factor for carboxylation of glutamic acid residues by vitamin K-dependent gamma-carboxylase in blood-clotting enzymes. Allelic variation in this gene is associated with vitamin k-dependent clotting factors combined deficiency of 2, and increased resistance or sensitivity to warfarin, an inhibitor of vitamin K epoxide reductase. Pseudogenes of this gene are located on chromosomes 1 and X. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 79001 — RefSeq curated summary.

At a glance

• Gene–disease (curated): coumarin resistance (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 54 total — 3 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 35
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_024006

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23663
Approved symbol	VKORC1
Name	vitamin K epoxide reductase complex subunit 1
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000167397
Ensembl biotype	protein_coding
OMIM	608547
Entrez	79001

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000300851, ENST00000319788, ENST00000354895, ENST00000394971, ENST00000394975, ENST00000420057, ENST00000472468, ENST00000498155, ENST00000879179, ENST00000879180

RefSeq mRNA: 3 — MANE Select: NM_024006 NM_001311311, NM_024006, NM_206824

CCDS: CCDS10703, CCDS10704

Canonical transcript exons

ENST00000394975 — 3 exons

Exon	Start	End
ENSE00001888159	31094557	31094797
ENSE00003465107	31093312	31093421
ENSE00003579391	31090854	31091342

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 130.7124 / max 816.9298, expressed in 1826 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157130	84.4410	1819
157132	33.1187	1820
157131	8.4504	1731
157128	4.1150	1325
157129	0.5873	350

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.04	gold quality
right lobe of liver	UBERON:0001114	99.00	gold quality
thoracic aorta	UBERON:0001515	98.59	gold quality
ascending aorta	UBERON:0001496	98.58	gold quality
descending thoracic aorta	UBERON:0002345	98.58	gold quality
right coronary artery	UBERON:0001625	98.47	gold quality
liver	UBERON:0002107	98.47	gold quality
body of pancreas	UBERON:0001150	98.40	gold quality
left coronary artery	UBERON:0001626	98.29	gold quality
pancreas	UBERON:0001264	98.04	gold quality
right ovary	UBERON:0002118	98.03	gold quality
pituitary gland	UBERON:0000007	98.02	gold quality
myometrium	UBERON:0001296	98.00	gold quality
popliteal artery	UBERON:0002250	97.94	gold quality
tibial artery	UBERON:0007610	97.94	gold quality
body of uterus	UBERON:0009853	97.90	gold quality
left ovary	UBERON:0002119	97.89	gold quality
right adrenal gland cortex	UBERON:0035827	97.83	gold quality
endocervix	UBERON:0000458	97.82	gold quality
left uterine tube	UBERON:0001303	97.82	gold quality
adenohypophysis	UBERON:0002196	97.81	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.76	gold quality
left adrenal gland cortex	UBERON:0035825	97.68	gold quality
right adrenal gland	UBERON:0001233	97.66	gold quality
islet of Langerhans	UBERON:0000006	97.65	gold quality
left adrenal gland	UBERON:0001234	97.65	gold quality
fundus of stomach	UBERON:0001160	97.57	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.49	gold quality
ovary	UBERON:0000992	97.47	gold quality
lower esophagus	UBERON:0013473	97.46	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-8322	yes	2053.79
E-MTAB-8410	yes	34.29
E-HCAD-6	yes	23.28
E-CURD-112	yes	6.20
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting VKORC1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-891A-3P	98.05	67.99	970
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-6860	97.21	66.31	1656
HSA-MIR-4313	97.18	63.15	420
HSA-MIR-6835-5P	95.81	64.27	500
HSA-MIR-4512	95.26	63.08	371

Literature-anchored findings (GeneRIF, showing 40)

• using a positional cloning approach that integrated mapping information from three species, the gene VKORC1 that is mutated in combined deficiency of vitamin-K-dependent clotting factors type 2 and warfarin resistance was identified (PMID:14765194)
• identification of the gene for VKOR based on specific inhibition of VKOR activity by a single siRNA pool (PMID:14765195)
• Genetic variants of the VKORC1 gene locus modulate the mean daily dose of drug prescribed to acquire the target anticoagulation intensity. (PMID:15358623)
• association between a nucleotide transition in VKORC1 and pharmacodynamic warfarin resistance supports the hypothesis that VKORC1 is the site of action of warfarin and indicates thatVKORC1 sequence is an important determinant of the warfarin dose response (PMID:15630486)
• The simple genotyping of 2 single-nucleotide polymorphisms (SNPs), VKORC1 -1639G>A or 1173C>T and the CYP2C9*3 polymorphisms, could thus predict a high risk of overdose before initiation of anticoagulation with acenocoumarol (PMID:15790782)
• VKORC1 single-nucleotide polymorphisms associated significantly with warfarin dose, and explain 29-30% of variance in dose. (PMID:15883587)
• VKORC1 haplotypes can be used to stratify patients into low-, intermediate-, and high-dose warfarin groups and may explain differences in dose requirements among patients of different ancestries. (PMID:15930419)
• CYP2C9 and VKORC1 genotype have roles in determining response to warfarin therapy and therefore in blood coagulation (PMID:15947090)
• VKOR is involved in angiogenesis. (PMID:15972850)
• a VKORC1 mutation is described in a patient with vitamin K antagonist resistance [case report] (PMID:15978113)
• Overexpression of VKORC1 can be utilized for increased cellular production of recombinant vitamin K-dependent proteins. (PMID:16030016)
• the C132-X-X-C135 motif in VKORC1 comprises part of the redox active site that catalyzes VKO reduction and also suggest a crucial role for the hydrophobic Thr-Tyr-Ala motif in coumarin binding (PMID:16270630)
• Population variation in VKORC1 haplotype structure. (PMID:16420583)
• VKORC1 and CYP2C9 polymorphisms contribute to inter-population difference in warfarin doses among Japanese, Caucasians and African-Americans (PMID:16424822)
• subjects with the CC and CT genotypes had lower levels of undercarboxylated osteocalcin, and lower levels of protein induced in vitamin K absence or antagonism than those with TT genotypes (PMID:16549638)
• The association between single nucleotide polymorphisms (SNPs) in VKORC1 and CYP2C9 and average weekly warfarin dose was tested. (PMID:16611750)
• These data indicate that the effect of VKOR overexpression is limited in vivo, possibly because a carboxylation component like the redox protein becomes saturated or because another step is now rate-limiting. (PMID:16634640)
• VKORC1 is the key protein of the vitamin K cycle [review] (PMID:16677080)
• VKORC1 1173C>T could be responsible, atleast in part, for the higher sensitivity of Asian people to oral anticoagulants. (PMID:16700826)
• VKORC1*2 is the most important haplotype for warfarin dosage in the Swedish population (PMID:16879214)
• In addition to polymorphisms in VKORC1 and CYP2C9, we identified GGCX 8016G>A, resulting in the missense mutation R325Q, as a genetic determinant of warfarin maintenance dose in Japanese patients. (PMID:17049586)
• Asp36Tyr is a new marker of the high end of the warfarin dosing range (PMID:17110455)
• Purified vitamin K epoxide reductase alone is sufficient for conversion of vitamin K epoxide to vitamin K and vitamin K to vitamin KH2. (PMID:17164330)
• Results suggest that knowledge of both VKORC1 and CYP2C9 genotypes could contribute to a safer treatment with along acting anticoagulant phenprocoumom. (PMID:17192772)
• VKORC1 haplotypes possibly are linked to some unidentified factors involved in the metabolic clearance of warfarin enantiomers (PMID:17413769)
• study examined the potential association between the functional SNP rs9923231 & early-onset coronary heart disease (CHD)in Northern Germans; no evidence for a significant association was detected between VKORC1 genotype & CHD phenotype (PMID:17549303)
• VKORC1 genotype did not confer a significant increase in risk for hemorrhage in patients on warfarin. (PMID:17653141)
• VKORC1 gene variation may not have a role in venous thrombosis [commentary] (PMID:17666014)
• VKORC1 (-1639) G/A genotyping might be necessary for patients with Factor V Leiden and/or prothrombin G2021A mutation before warfarin anticoagulant therapy. (PMID:17721328)
• Mutations and single nucleotide polymorphisms within the translated and non-translated regions of the VKORC1 gene have been shown to cause coumarin resistance and sensitivity, respectively. (PMID:17849045)
• the VKORCI polymorphism may have a role in the pathogenesis of venous thromboembolism (PMID:17883698)
• VKORC1 variants are not associated with arterial or venous thrombosis (PMID:17883699)
• Warfarin dose requirements in Asian patients homozygous for VKORC1 H1 haplotype are significantly lower compared with patients homozygous for the H7 haplotype. (PMID:17995970)
• VKORC1 protein genotype was not associated with warfarin dose requirements in the African-Americans population. (PMID:18034618)
• T allele of VKORC1 1173C>T SNP (tag-SNP of H1-H2 haplotypes) is highly associated with low mean weekly warfarin dose. (PMID:18034619)
• Persons with at least one 1173C>T-allele had a statistically significant 19% (95% CI 2 to 40%) risk increase of calcification of the aortic far wall compared to CC homozygous persons, adjusted for age and gender. (PMID:18218987)
• Single nucleotide polymorphisms show significant differences between ethnic groups and are associated with warfarin dose requirements for achieving a recommended International Normalized Ratio range in Japanese cardiovascular surgery patients. (PMID:18240904)
• Initial variability in the INR response to warfarin was more strongly associated with genetic variability in the pharmacologic target of warfarin, VKORC1, than with CYP2C9. (PMID:18322281)
• No clear link waqs found between VKORC1 genetic polymorphism and the risk of venous thrombosis or peripheral arterial disease. (PMID:18449434)
• effect of VKORC1 genotype on vitamin K-induced alterations in the anticoagulation response (PMID:18466315)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	vkorc1	ENSDARG00000086183
mus_musculus	Vkorc1	ENSMUSG00000096145
drosophila_melanogaster	Vkor	FBGN0053544

Paralogs (1): VKORC1L1 (ENSG00000196715)

Protein

Protein identifiers

Vitamin K epoxide reductase complex subunit 1 — Q9BQB6 (reviewed: Q9BQB6)

Alternative names: Vitamin K1 2,3-epoxide reductase subunit 1

All UniProt accessions (8): A0A0S2Z5X7, A0A0S2Z6I4, Q9BQB6, A8MV79, F2Z3Q2, F8W9H0, H0YF24, I3L1P9

UniProt curated annotations — full annotation on UniProt →

Function. Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the gamma-carboxylation of various proteins, including clotting factors, and is required for normal blood coagulation, but also for normal bone development.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expressed at highest levels in fetal and adult liver, followed by fetal heart, kidney, and lung, adult heart, and pancreas.

Disease relevance. Combined deficiency of vitamin K-dependent clotting factors 2 (VKCFD2) [MIM:607473] VKCFD leads to a bleeding tendency that is usually reversed by oral administration of vitamin K. The disease is caused by variants affecting the gene represented in this entry. Coumarin resistance (CMRES) [MIM:122700] A condition characterized by partial or complete resistance to warfarin or other 4-hydroxycoumarin derivatives. These drugs are used as anti-coagulants for the prevention of thromboembolic diseases in subjects with deep vein thrombosis, atrial fibrillation, or mechanical heart valve replacement. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by warfarin (coumadin). Warfarin locks VKORC1 in both redox states into the closed conformation. Inhibited by warfarin analogs phenindione, brodifacoum and chlorophacinone.

Domain organisation. Partially oxidized VKORC1 forms a cysteine adduct with substrates, vitamin K 2,3-epoxide, inducing a closed conformation, juxtaposing all cysteines (S-S or SH) for unimpeded electron transfer. VKOR becomes fully oxidized with an open conformation that releases reaction products, vitamin K quinone, or hydroquinone. Cys-132 and Cys-135 constitute the catalytic redox-active center. Cys-43 and Cys-51 are the cysteine pair that mediates transfer of reducing equivalents during catalysis.

Similarity. Belongs to the VKOR family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BQB6-1	1, MST576	yes
Q9BQB6-2	2, MST134
Q9BQB6-3	3

RefSeq proteins (3): NP_001298240, NP_076869, NP_996560 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012932	VKOR	Domain
IPR038354	VKOR_sf	Homologous_superfamily
IPR042406	VKORC1/VKORC1L1	Family

Pfam: PF07884

Enzyme classification (BRENDA):

• EC 1.17.4.4 — vitamin-K-epoxide reductase (warfarin-sensitive) (BRENDA: 25 organisms, 68 substrates, 97 inhibitors, 39 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
2,3-EPOXY-2,3-DIHYDRO-2-METHYL-3-PHYTYL-1,4-NAPH	0.0043–0.1875	12
VITAMIN K1 2,3-EPOXIDE	0.0024–0.0065	7
2-METHYL-3-PHYTYL-1,4-NAPHTHOQUINONE	0.0072–0.0195	4
VITAMIN K 2,3-EPOXIDE	0.0013–0.0052	4
DITHIOTHREITOL	0.0004–0.16	3
2,3-EPOXYPHYLLOQUINONE	0.0178–0.0195	2
ALLYLBENZENE 2’,3’-OXIDE	0.805	1
STYRENE 1’,2’-OXIDE	0.065	1

Catalyzed reactions (Rhea), 2 shown:

• phylloquinone + [protein]-disulfide + H2O = 2,3-epoxyphylloquinone + [protein]-dithiol (RHEA:13817)
• phylloquinol + [protein]-disulfide = phylloquinone + [protein]-dithiol (RHEA:57744)

UniProt features (66 total): sequence variant 19, mutagenesis site 19, helix 9, topological domain 5, binding site 4, transmembrane region 4, disulfide bond 2, splice variant 2, chain 1, strand 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
6WVH	X-RAY DIFFRACTION	1.99
6WV3	X-RAY DIFFRACTION	2.2
6WV7	X-RAY DIFFRACTION	2.48
6WV6	X-RAY DIFFRACTION	2.7
6WV5	X-RAY DIFFRACTION	2.8
6WV4	X-RAY DIFFRACTION	3.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQB6-F1	91.50	0.82

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 80; 135; 139; 139

Disulfide bonds (2): 43–51, 132–135

Mutagenesis-validated functional residues (19):

Position	Phenotype
16	reduces enzyme activity by about 80%.
35	nearly abolishes enzyme activity.
43	reduces enzyme activity.
51	reduces enzyme activity.
56	nearly abolishes enzyme activity.
57	nearly abolishes enzyme activity.
80	decreased vitamin k epoxide reductase activity.
85	reduces enzyme activity by about 25%.
85	reduces enzyme activity by about 75%.
96	reduces enzyme activity by about 70%.
98	reduces enzyme activity by about 80%. decreases inhibition by warfarin.
98	no effect on enzyme activity. decreases inhibition by warfarin.
120	decreases enzyme activity moderately. decreases inhibition by warfarin.
128	decreases enzyme activity by about 80%. decreases inhibition by warfarin.
132	nearly abolishes enzyme activity.
135	nearly abolishes enzyme activity.
139	decreased vitamin k epoxide reductase activity.
139	decreases enzyme activity moderately. strongly decreases inhibition by warfarin.
139	no effect on enzyme activity. strongly decreases inhibition by warfarin.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6806664	Metabolism of vitamin K

MSigDB gene sets: 272 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_COAGULATION, GOLDRATH_IMMUNE_MEMORY, GOBP_POSITIVE_REGULATION_OF_COAGULATION, GOBP_KETONE_METABOLIC_PROCESS, GOBP_WOUND_HEALING, GOBP_BONE_DEVELOPMENT, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, chr16p11, MORI_SMALL_PRE_BII_LYMPHOCYTE_DN, GOBP_PEPTIDYL_GLUTAMIC_ACID_MODIFICATION, GOBP_HEMOSTASIS, DELASERNA_MYOD_TARGETS_UP

GO Biological Process (6): xenobiotic metabolic process (GO:0006805), blood coagulation (GO:0007596), peptidyl-glutamic acid carboxylation (GO:0017187), vitamin K metabolic process (GO:0042373), positive regulation of coagulation (GO:0050820), bone development (GO:0060348)

GO Molecular Function (6): vitamin-K-epoxide reductase (warfarin-sensitive) activity (GO:0047057), vitamin-K-epoxide reductase (warfarin-insensitive) activity (GO:0047058), quinone binding (GO:0048038), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on CH or CH2 groups, disulfide as acceptor (GO:0016728)

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of fat-soluble vitamins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
coagulation	2
oxidoreductase activity, acting on CH or CH2 groups, disulfide as acceptor	2
metabolic process	1
cellular response to xenobiotic stimulus	1
hemostasis	1
wound healing	1
peptidyl-glutamic acid modification	1
protein carboxylation	1
ketone metabolic process	1
regulation of coagulation	1
positive regulation of multicellular organismal process	1
skeletal system development	1
animal organ development	1
small molecule binding	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on CH or CH2 groups	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
endoplasmic reticulum	1
intracellular organelle lumen	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

754 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VKORC1	GGCX	P38435	988
VKORC1	CYP2C9	P11712	980
VKORC1	CYP4F2	P78329	967
VKORC1	CYP2C19	P33259	914
VKORC1	PROS1	P07225	856
VKORC1	MGP	P08493	848
VKORC1	F2	P00734	831
VKORC1	ABCC6	P78420	824
VKORC1	CYP2C8	P10632	809
VKORC1	CALU	O43852	809
VKORC1	F7	P08709	791
VKORC1	TPMT	P51580	786
VKORC1	SLCO1B1	Q9Y6L6	785
VKORC1	CYP2D6	P10635	769
VKORC1	EPHX1	P07099	766

IntAct

98 interactions, top by confidence:

A	B	Type	Score
VKORC1	SDC3	psi-mi:“MI:0915”(physical association)	0.560
VKORC1	BIK	psi-mi:“MI:0915”(physical association)	0.560
VKORC1	TMPRSS2	psi-mi:“MI:0915”(physical association)	0.560
VKORC1	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
VKORC1	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
VKORC1	RMDN3	psi-mi:“MI:0915”(physical association)	0.560
VKORC1	FAM210B	psi-mi:“MI:0915”(physical association)	0.560
SDC3	VKORC1	psi-mi:“MI:0915”(physical association)	0.560
BIK	VKORC1	psi-mi:“MI:0915”(physical association)	0.560
TMPRSS2	VKORC1	psi-mi:“MI:0915”(physical association)	0.560
CREB3L1	VKORC1	psi-mi:“MI:0915”(physical association)	0.560
FAM210B	VKORC1	psi-mi:“MI:0915”(physical association)	0.560
GORAB	VKORC1	psi-mi:“MI:0915”(physical association)	0.560
FAM209A	VKORC1	psi-mi:“MI:0915”(physical association)	0.560
SLC7A14	VKORC1	psi-mi:“MI:0915”(physical association)	0.560
CPLX4	VKORC1	psi-mi:“MI:0915”(physical association)	0.560
MUC1	VKORC1	psi-mi:“MI:0915”(physical association)	0.560
RMDN3	VKORC1	psi-mi:“MI:0915”(physical association)	0.560
VKORC1	MANBAL	psi-mi:“MI:0915”(physical association)	0.560
GPR152	VKORC1	psi-mi:“MI:0915”(physical association)	0.560
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530

BioGRID (157): VKORC1 (Two-hybrid), VKORC1 (Affinity Capture-MS), VKORC1 (Affinity Capture-MS), VKORC1 (Affinity Capture-MS), VKORC1 (Affinity Capture-MS), VKORC1 (Affinity Capture-MS), VKORC1 (Affinity Capture-MS), VKORC1 (Affinity Capture-MS), VKORC1 (Affinity Capture-MS), VKORC1 (Affinity Capture-MS), VKORC1 (Affinity Capture-MS), VKORC1 (Affinity Capture-MS), VKORC1 (Affinity Capture-MS), VKORC1 (Affinity Capture-MS), VKORC1 (Two-hybrid)

ESM2 similar proteins: A0A2I1C3V3, A0A411PQQ5, A4DA85, E2RDM9, M1VWN5, M3APK4, O18765, O28797, O82245, O94327, P0DN89, P16257, P17057, P24008, P30535, P30536, P31213, P31214, P50637, P70245, Q15125, Q28892, Q2QDF6, Q3MHQ7, Q3T0W0, Q3T100, Q3ZCI1, Q4WQY6, Q5R751, Q5R9A6, Q5REM8, Q5TGU0, Q5U220, Q6B4J2, Q6DFQ5, Q6UN27, Q6UW68, Q8HZJ2, Q8KBX2, Q8N2M4

Diamond homologs: Q6B4J2, Q6TEK3, Q6TEK4, Q6TEK5, Q6TEK8, Q8N0U8, Q9BQB6, Q9CRC0

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
VKORC1	“down-regulates quantity”	“vitamin K epoxide”	“chemical modification”
VKORC1	“up-regulates quantity”	“Reduced Vitamin K”	“chemical modification”
VKORC1	“down-regulates quantity”	“vitamin K”	“chemical modification”
warfarin	“down-regulates activity”	VKORC1	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

54 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	23
Likely benign	5
Benign	6

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
2207	NM_024006.6(VKORC1):c.85G>T (p.Val29Leu)	Pathogenic
2208	NM_024006.6(VKORC1):c.134T>C (p.Val45Ala)	Pathogenic
2209	NM_024006.6(VKORC1):c.172A>G (p.Arg58Gly)	Pathogenic
2206	NM_024006.6(VKORC1):c.292C>T (p.Arg98Trp)	Likely pathogenic
3381146	NM_024006.6(VKORC1):c.229A>T (p.Asn77Tyr)	Likely pathogenic

SpliceAI

667 predictions. Top by Δscore:

Variant	Effect	Δscore
16:31091136:AGTG:A	donor_gain	1.0000
16:31091146:AG:A	donor_gain	1.0000
16:31091147:G:C	donor_gain	1.0000
16:31094553:ACACC:A	donor_loss	1.0000
16:31094554:CACC:C	donor_loss	1.0000
16:31094555:ACC:A	donor_loss	1.0000
16:31094556:CC:C	donor_loss	1.0000
16:31091139:G:A	donor_gain	0.9900
16:31091152:G:A	donor_gain	0.9900
16:31091172:T:TA	donor_gain	0.9900
16:31091181:TGAGC:T	donor_gain	0.9900
16:31091226:CAATG:C	donor_gain	0.9900
16:31091343:C:CC	acceptor_gain	0.9900
16:31091343:CTGCA:C	acceptor_loss	0.9900
16:31091344:T:A	acceptor_loss	0.9900
16:31094546:C:CA	donor_gain	0.9900
16:31094552:CACA:C	donor_loss	0.9900
16:31094553:ACAC:A	donor_loss	0.9900
16:31094555:A:T	donor_loss	0.9900
16:31094556:C:A	donor_loss	0.9900
16:31091198:A:AC	donor_gain	0.9800
16:31091199:C:CC	donor_gain	0.9800
16:31091225:A:AC	donor_gain	0.9800
16:31091226:C:CC	donor_gain	0.9800
16:31091339:CAAC:C	acceptor_gain	0.9800
16:31091340:AAC:A	acceptor_gain	0.9800
16:31091341:AC:A	acceptor_gain	0.9800
16:31091342:CC:C	acceptor_gain	0.9800
16:31091343:C:A	acceptor_loss	0.9800
16:31094578:CAG:C	donor_gain	0.9800

AlphaMissense

1043 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:31093352:G:C	S81R	0.982
16:31093352:G:T	S81R	0.982
16:31093354:T:G	S81R	0.982
16:31093334:G:C	F87L	0.980
16:31093334:G:T	F87L	0.980
16:31093336:A:G	F87L	0.980
16:31093404:C:T	G64E	0.980
16:31093355:G:C	N80K	0.979
16:31093355:G:T	N80K	0.979
16:31091231:C:T	C132Y	0.977
16:31093411:C:G	G62R	0.972
16:31091200:G:C	N142K	0.971
16:31091200:G:T	N142K	0.971
16:31094565:G:C	F55L	0.971
16:31094565:G:T	F55L	0.971
16:31094567:A:G	F55L	0.971
16:31093406:G:C	F63L	0.970
16:31093406:G:T	F63L	0.970
16:31093408:A:G	F63L	0.970
16:31093344:C:T	G84D	0.969
16:31093418:C:A	W59C	0.969
16:31093418:C:G	W59C	0.969
16:31094602:C:G	C43S	0.969
16:31094603:A:T	C43S	0.969
16:31091299:G:C	S109R	0.968
16:31091299:G:T	S109R	0.968
16:31091301:T:G	S109R	0.968
16:31093342:A:G	C85R	0.966
16:31094566:A:C	F55C	0.966
16:31094602:C:T	C43Y	0.966

dbSNP variants (sampled 300 via entrez): RS1000020242 (16:31093957 G>T), RS1000983632 (16:31095483 C>T), RS1001467846 (16:31095215 C>T), RS1001639264 (16:31092651 T>C,G), RS1001690297 (16:31092344 G>A,T), RS1002747237 (16:31095984 C>A), RS1003310348 (16:31090971 G>A,C), RS1003983905 (16:31091079 A>G,T), RS1004016466 (16:31090763 C>A,G), RS1004095378 (16:31094871 T>G), RS1005505257 (16:31096511 G>A), RS1005651686 (16:31092875 AAAAAAC>A), RS1006094261 (16:31092537 C>T), RS1006651003 (16:31096624 G>A), RS1007903968 (16:31094946 T>C,G)

Disease associations

OMIM: gene MIM:608547 | disease phenotypes: MIM:122700, MIM:607473, MIM:277450

GenCC curated gene-disease

Disease	Classification	Inheritance
vitamin K-dependent clotting factors, combined deficiency of, type 2	Strong	Autosomal recessive
coumarin resistance	Strong	Autosomal dominant
vitamin K-dependent clotting factors, combined deficiency of, type 1	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
vitamin K-dependent clotting factors, combined deficiency of, type 2	Moderate	AR

Mondo (5): coumarin resistance (MONDO:0007390), vitamin K-dependent clotting factors, combined deficiency of, type 2 (MONDO:0011837), congenital vitamin K-dependent coagulation factors deficiency (MONDO:0015722), venous thromboembolism (MONDO:0005399), vitamin K-dependent clotting factors, combined deficiency of, type 1 (MONDO:0010187)

Orphanet (2): Congenital vitamin K-dependent coagulation factors deficiency (Orphanet:169826), Hereditary combined deficiency of vitamin K-dependent clotting factors (Orphanet:98434)

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000132	Menorrhagia
HP:0000421	Epistaxis
HP:0000939	Osteoporosis
HP:0000973	Cutis laxa
HP:0000978	Bruising susceptibility
HP:0001102	Angioid streaks
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001871	Abnormality of blood and blood-forming tissues
HP:0001892	Abnormal bleeding
HP:0002170	Intracranial hemorrhage
HP:0002239	Gastrointestinal hemorrhage
HP:0002621	Atherosclerosis
HP:0003645	Prolonged partial thromboplastin time
HP:0004415	Pulmonary artery stenosis
HP:0004646	Hypoplasia of the nasal bone
HP:0004855	Reduced protein S activity
HP:0005261	Joint hemorrhage
HP:0005543	Reduced protein C activity
HP:0006118	Shortening of all distal phalanges of the fingers
HP:0008151	Prolonged prothrombin time
HP:0008169	Reduced factor VII activity
HP:0008321	Reduced factor X activity
HP:0010655	Epiphyseal stippling
HP:0011858	Reduced factor IX activity
HP:0011884	Abnormal umbilical stump bleeding
HP:0011890	Prolonged bleeding following procedure
HP:0011891	Post-partum hemorrhage

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000204_1	Warfarin maintenance dose	5.000000e-34
GCST000360_1	Warfarin maintenance dose	3.000000e-181
GCST000792_4	Warfarin maintenance dose	9.000000e-31
GCST003085_8	Warfarin maintenance dose	1.000000e-33
GCST007293_141	Body fat distribution (arm fat ratio)	4.000000e-15
GCST007293_82	Body fat distribution (arm fat ratio)	3.000000e-15
GCST007293_99	Body fat distribution (arm fat ratio)	1.000000e-14
GCST008103_175	Bipolar disorder	8.000000e-06
GCST008115_45	Bipolar I disorder	5.000000e-07
GCST008374_3	Warfarin maintenance dose (adjusted for clinical factors)	5.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0009963	bipolar I disorder

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D054556	Venous Thromboembolism	C14.907.355.590.700
C563039	Coumarin Resistance (supp.)
C564741	Vitamin K-Dependent Clotting Factors, Combined Deficiency Of, 1 (supp.)
C564393	Vitamin K-Dependent Clotting Factors, Combined Deficiency Of, Type 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1930 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 69,797 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1464	WARFARIN	4	69,797

PharmGKB: 1 entry (VIP=true, CPIC=true)

PharmGKB clinical annotations

38 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs104894539	Dosage	3	warfarin
rs104894540	Dosage	3	warfarin
rs104894541	Dosage	3	warfarin
rs104894542	Dosage	3	warfarin
rs11150606	Dosage	3	warfarin
rs17708472	Dosage	4	warfarin
rs17878544	Dosage	3	acenocoumarol
rs17880887	Dosage	3	warfarin
rs17886199	Dosage	3	warfarin
rs2359612	Dosage	1B	warfarin
rs2884737	Dosage	2A	warfarin
rs55894764	Dosage	3	acenocoumarol
rs61162043	Dosage	3	warfarin
rs61742245	Dosage	2A	warfarin
rs61742245	Dosage	3	acenocoumarol
rs7196161	Dosage	3	warfarin
rs7200749	Dosage	3	warfarin
rs7200749	Dosage	3	acenocoumarol
rs72547529	Dosage,Efficacy	3	warfarin
rs7294	Dosage	1B	warfarin
rs7294	Other	3	acenocoumarol
rs7294	Dosage	3	acenocoumarol;phenprocoumon
rs8050894	Dosage	1B	warfarin
rs9923231	Dosage	1A	phenprocoumon
rs9923231	Dosage	1A	acenocoumarol
rs9923231	Dosage	1A	warfarin
rs9923231	Toxicity	1B	warfarin	over-anticoagulation
rs9923231	Efficacy	2A	warfarin	time to therapeutic inr
rs9923231	Efficacy	2A	warfarin	time in therapeutic range
rs9923231	Toxicity	2A	warfarin	Hemorrhage
rs9923231	Toxicity	2A	phenprocoumon	Hemorrhage;over-anticoagulation;time above therapeutic range
rs9923231	Toxicity	3	acenocoumarol	Hemorrhage
rs9934438	Dosage	1B	warfarin
rs9934438	Dosage	2A	phenprocoumon
rs9934438	Dosage	2A	acenocoumarol
rs9934438	Efficacy	3	warfarin
rs9934438	Efficacy	3	fluindione	Thromboembolism

PharmGKB variants

24 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7294	PRSS53, VKORC1	1B	43.25	3	acenocoumarol;acenocoumarol;phenprocoumon;warfarin
rs749671	VKORC1, ZNF646		0.00	0
rs2359612	PRSS53, VKORC1	1B	38.25	1	warfarin
rs2884737	VKORC1	2A	11.25	1	warfarin
rs7196161	VKORC1	3	3.50	1	warfarin
rs7200749	PRSS53, VKORC1	3	3.00	2	acenocoumarol;warfarin
rs8050894	VKORC1	1B	27.00	1	warfarin
rs9923231	BCKDK, PRSS53, VKORC1	1A	484.38	9	warfarin;acenocoumarol;phenprocoumon
rs9934438	PRSS53, VKORC1	1B	109.62	6	warfarin;fluindione;acenocoumarol;phenprocoumon
rs11150606	PRSS53, VKORC1	3	2.00	1	warfarin
rs17708472	VKORC1	4	-2.00	1	warfarin
rs17878544	VKORC1	3	3.00	1	acenocoumarol
rs17880887	VKORC1	3	2.25	1	warfarin
rs17886199	PRSS53, VKORC1	3	2.00	1	warfarin
rs55894764	VKORC1	3	3.00	1	acenocoumarol
rs56314408	VKORC1		0.00	0
rs61162043	BCKDK, VKORC1	3	2.75	1	warfarin
rs61742245	PRSS53, VKORC1	2A	7.25	2	acenocoumarol;warfarin
rs72547529	VKORC1	3	1.00	1	warfarin
rs104894539	VKORC1	3	0.25	1	warfarin
rs104894540	VKORC1	3	0.25	1	warfarin
rs104894541	VKORC1	3	0.25	1	warfarin
rs104894542	PRSS53, VKORC1	3	0.25	1	warfarin
rs188009042	VKORC1		0.00	0

PharmGKB dosing guidelines

6 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
CPIC	warfarin	Annotation of CPIC Guideline for warfarin and CYP2C9, CYP4F2, VKORC1	yes	yes
DPWG	acenocoumarol	Annotation of DPWG Guideline for acenocoumarol and VKORC1	yes	yes
DPWG	phenprocoumon	Annotation of DPWG Guideline for phenprocoumon and VKORC1	yes	yes
DPWG	warfarin	Annotation of DPWG Guideline for warfarin and VKORC1	yes	yes
CPNDS	warfarin	Annotation of CPNDS Guideline for warfarin and CYP2C9, VKORC1	yes	yes
RNPGx	acenocoumarol;fluindione;warfarin	Annotation of RNPGx Guideline for acenocoumarol, fluindione, warfarin and CYP2C9, VKORC1	yes	yes

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 1.-.-.- Oxidoreductases

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
acenocoumarol	Inhibition	6.11	pIC50
warfarin	Inhibition	5.58	pKi

ChEMBL bioactivities

16 potent at pChembl≥5 of 23 total, top 16 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.35	IC50	4.5	nM	CHEMBL4594145
8.06	IC50	8.8	nM	WARFARIN
7.24	IC50	58.2	nM	CHEMBL4530669
7.23	IC50	59	nM	CHEMBL4517532
7.04	IC50	90.2	nM	CHEMBL4443961
7.01	IC50	98	nM	CHEMBL5435296
6.82	IC50	150	nM	BRODIFACOUM
6.30	IC50	498	nM	CHEMBL5436380
6.28	IC50	527	nM	CHEMBL5433796
6.19	IC50	643	nM	CHEMBL5432023
6.06	IC50	873	nM	CHEMBL5403819
5.97	IC50	1059	nM	WARFARIN
5.81	IC50	1534	nM	CHEMBL5404461
5.71	IC50	1929	nM	CHEMBL4463800
5.57	IC50	2715	nM	CHEMBL5434421
5.26	IC50	5535	nM	CHEMBL5396437

PubChem BioAssay actives

17 with measured affinity, of 31 total; 15 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-(cyclooctatetraenyl)-2-hydroxy-2-methyl-3,4-dihydropyrano[3,2-c]chromen-5-one	1633844: Inhibition of VKOR (unknown origin) in HEK293 expressing FIXgla-PC incubated for 48 hrs by ELISA	ic50	0.0045	uM
Warfarin	1633844: Inhibition of VKOR (unknown origin) in HEK293 expressing FIXgla-PC incubated for 48 hrs by ELISA	ic50	0.0088	uM
(3R,6’R,8’S)-6’-(cyclooctatetraenyl)-8’-hydroxy-8’-methyl-2’-phenylspiro[2H-chromene-3,5’-6,7-dihydro-[1,2,4]triazolo[1,2-a]pyridazine]-1’,3’,4-trione	1633844: Inhibition of VKOR (unknown origin) in HEK293 expressing FIXgla-PC incubated for 48 hrs by ELISA	ic50	0.0582	uM
3-(1-cyclooctyl-3-oxobutyl)-4-hydroxychromen-2-one	1633844: Inhibition of VKOR (unknown origin) in HEK293 expressing FIXgla-PC incubated for 48 hrs by ELISA	ic50	0.0590	uM
3-(1-cyclohexyl-3-oxobutyl)-4-hydroxychromen-2-one	1633844: Inhibition of VKOR (unknown origin) in HEK293 expressing FIXgla-PC incubated for 48 hrs by ELISA	ic50	0.0902	uM
4-hydroxy-3-[(2Z,6Z)-3,7,11-trimethyldodeca-2,6,10-trienyl]chromen-2-one	2015651: Inhibition of recombinant human wild-type VKORC1 expressed in Pichia pastoris membrane incubated for 30 mins in presence of presence of dithiothreitol by LC-APCI/MS/MS analysis	ic50	0.0980	uM
3-[3-[4-(4-bromophenyl)phenyl]-1,2,3,4-tetrahydronaphthalen-1-yl]-4-hydroxychromen-2-one	2015651: Inhibition of recombinant human wild-type VKORC1 expressed in Pichia pastoris membrane incubated for 30 mins in presence of presence of dithiothreitol by LC-APCI/MS/MS analysis	ic50	0.1500	uM
4-hydroxy-3-[[4-(trifluoromethyl)phenyl]methyl]chromen-2-one	2015651: Inhibition of recombinant human wild-type VKORC1 expressed in Pichia pastoris membrane incubated for 30 mins in presence of presence of dithiothreitol by LC-APCI/MS/MS analysis	ic50	0.4980	uM
4-hydroxy-3-[(4-methylsulfanylphenyl)methyl]chromen-2-one	2015651: Inhibition of recombinant human wild-type VKORC1 expressed in Pichia pastoris membrane incubated for 30 mins in presence of presence of dithiothreitol by LC-APCI/MS/MS analysis	ic50	0.5270	uM
3-[(4-bromophenyl)methyl]-4-hydroxychromen-2-one	2015651: Inhibition of recombinant human wild-type VKORC1 expressed in Pichia pastoris membrane incubated for 30 mins in presence of presence of dithiothreitol by LC-APCI/MS/MS analysis	ic50	0.6430	uM
3-(1,3-benzodioxol-5-ylmethyl)-4-hydroxychromen-2-one	2015651: Inhibition of recombinant human wild-type VKORC1 expressed in Pichia pastoris membrane incubated for 30 mins in presence of presence of dithiothreitol by LC-APCI/MS/MS analysis	ic50	0.8730	uM
4-hydroxy-3-(1-phenylethyl)chromen-2-one	2015651: Inhibition of recombinant human wild-type VKORC1 expressed in Pichia pastoris membrane incubated for 30 mins in presence of presence of dithiothreitol by LC-APCI/MS/MS analysis	ic50	1.5340	uM
(1E,3Z,5E,7Z)-6-[1-(4-hydroxy-2-oxochromen-3-yl)-3-oxobutyl]cycloocta-1,3,5,7-tetraene-1-carboxylic acid	1633844: Inhibition of VKOR (unknown origin) in HEK293 expressing FIXgla-PC incubated for 48 hrs by ELISA	ic50	1.9290	uM
4-hydroxy-3-[(4-methoxyphenyl)methyl]chromen-2-one	2015651: Inhibition of recombinant human wild-type VKORC1 expressed in Pichia pastoris membrane incubated for 30 mins in presence of presence of dithiothreitol by LC-APCI/MS/MS analysis	ic50	2.7150	uM
4-hydroxy-3-[(3-methoxyphenyl)methyl]chromen-2-one	2015651: Inhibition of recombinant human wild-type VKORC1 expressed in Pichia pastoris membrane incubated for 30 mins in presence of presence of dithiothreitol by LC-APCI/MS/MS analysis	ic50	5.5350	uM

CTD chemical–gene interactions

55 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Warfarin	affects cotreatment, affects response to substance, decreases response to substance, affects abundance, affects metabolic processing (+6 more)	163
Acenocoumarol	decreases activity, affects response to substance, decreases response to substance, increases response to substance, decreases reaction (+1 more)	12
Phenprocoumon	decreases reaction, increases reduction, decreases activity, affects response to substance, decreases response to substance	5
Valproic Acid	affects cotreatment, increases expression, affects expression	4
Benzo(a)pyrene	decreases expression, increases methylation	3
bisphenol A	affects expression, affects cotreatment, increases expression	2
vitamin K1 oxide	decreases reaction, increases reduction, increases activity, increases carboxylation	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
coumarin	decreases response to substance, increases response to substance	2
bisphenol F	affects cotreatment, increases expression	1
coumatetralyl	decreases reaction, increases reduction, decreases activity	1
triphenyl phosphate	affects expression	1
bromfenacoum	decreases reaction, increases reduction, decreases activity	1
fluindione	decreases reaction, increases reduction, decreases activity	1
bromadiolone	decreases reaction, increases reduction, decreases activity	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-hydroxycoumarin	decreases reaction, increases reduction, decreases activity	1
7-hydroxywarfarin	affects abundance	1
ferulenol	decreases reaction, increases reduction, decreases activity	1
chloropicrin	increases expression	1
K 7174	decreases expression	1
coumachlor	decreases reaction, increases reduction, decreases activity	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
pyrimidifen	increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2051036	Binding	Inhibition of VKORC1	Biochemical and pharmacological evaluation of 4-hydroxychromen-2-ones bearing polar C-3 substituents as anticoagulants. — Eur J Med Chem

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2L3	Abcam HeLa VKORC1 KO	Cancer cell line	Female
CVCL_B3L8	Abcam HEK293T VKORC1 KO	Transformed cell line	Female
CVCL_TX45	HAP1 VKORC1 (-) 1	Cancer cell line	Male
CVCL_TX46	HAP1 VKORC1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00077753	PHASE4	COMPLETED	EXCLAIM:Extended Prophylaxis for Venous ThromboEmbolism (VTE) in Acutely Ill Medical Patients With Prolonged Immobilization
NCT00196118	PHASE4	COMPLETED	Study of IVC Filter Retrieval With the Günther Tulip Vena Cava Filter
NCT00437697	PHASE4	TERMINATED	Thromboprophylaxis in Critically Ill Patients
NCT00445328	PHASE4	TERMINATED	Dalteparin vs Unfractionated Heparin For The Prevention Of Venous Thromboembolism (VTE) In Hospitalized Acutely Ill Medical Patients
NCT00689520	PHASE4	COMPLETED	Long-Term Low-Molecular-Weight Heparin Versus Oral Anticoagulants in Deep Venous Thrombosis
NCT00851864	PHASE4	COMPLETED	Safety and Efficacy of Therapeutic Anticoagulation With Tinzaparin During Pregnancy Via Weight-based Dosing
NCT00966277	PHASE4	COMPLETED	Dalteparin for Primary Venous Thromboembolism (VTE) Prophylaxis in Pancreatic Cancer Patients
NCT00967304	PHASE4	COMPLETED	Clinical Decision Rule Validation Study to Predict Low Recurrent Risk in Patients With Unprovoked Venous Thromboembolism
NCT01119261	PHASE4	COMPLETED	EUropean Pharmacogenetics of AntiCoagulant Therapy - Acenocoumarol
NCT01119274	PHASE4	COMPLETED	EUropean Pharmacogenetics of AntiCoagulant Therapy - Phenprocoumon
NCT01119300	PHASE4	COMPLETED	EUropean Pharmacogenetics of AntiCoagulant Therapy - Warfarin
NCT01210755	PHASE4	COMPLETED	Study in Healthy Volunteers of the Reversion by Haemostatic Drugs of the Anticoagulant Effect of New Anti-thrombotics
NCT01304108	PHASE4	COMPLETED	Improving Venous Thromboembolism Prophylaxis
NCT01467583	PHASE4	COMPLETED	Fondaparinux in Critically Ill Patients With Renal Failure
NCT01916707	PHASE4	UNKNOWN	Weight Based Enoxaparin in Trauma Patients
NCT02095509	PHASE4	COMPLETED	Pharmacokinetics of Enoxaparin in Intensive Care Patients
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