VKORC1L1

Summary

VKORC1L1 (vitamin K epoxide reductase complex subunit 1L1, HGNC:21492) is a protein-coding gene on chromosome 7q11.21, encoding Vitamin K epoxide reductase complex subunit 1-like protein 1 (Q8N0U8). Involved in vitamin K metabolism.

This gene encodes an enzyme important in the vitamin K cycle, which is involved in the carboxylation of glutamate residues present in vitamin K-dependent proteins. The encoded enzyme catalyzes the de-epoxidation of vitamin K 2,3-epoxide. Oxidative stress may upregulate expression of this gene and the encoded protein may protect cells and membrane proteins form oxidative damage. This gene and a related gene (Gene ID: 79001) may have arisen by gene duplication of an ancestral gene.

Source: NCBI Gene 154807 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 14 total
• Druggable target: yes
• MANE Select transcript: NM_173517

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21492
Approved symbol	VKORC1L1
Name	vitamin K epoxide reductase complex subunit 1L1
Location	7q11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196715
Ensembl biotype	protein_coding
OMIM	608838
Entrez	154807

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000360768, ENST00000434382, ENST00000648179, ENST00000648187, ENST00000880557, ENST00000880558, ENST00000880559, ENST00000962252

RefSeq mRNA: 2 — MANE Select: NM_173517 NM_001284342, NM_173517

CCDS: CCDS5529, CCDS64663

Canonical transcript exons

ENST00000360768 — 3 exons

Exon	Start	End
ENSE00001408788	65948671	65948780
ENSE00003846291	65873074	65873565
ENSE00003847337	65954074	65959558

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 91.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.3846 / max 264.9467, expressed in 1770 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78845	4.7003	1531
78843	3.5311	1550
78846	1.8301	1004
78842	0.6247	340
78849	0.3788	162
78844	0.3196	128

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adipose tissue	UBERON:0001013	91.52	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.95	gold quality
upper arm skin	UBERON:0004263	89.61	gold quality
skin of hip	UBERON:0001554	89.60	gold quality
tibialis anterior	UBERON:0001385	89.59	gold quality
deltoid	UBERON:0001476	89.28	gold quality
left ventricle myocardium	UBERON:0006566	88.74	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.45	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.26	gold quality
omental fat pad	UBERON:0010414	87.99	gold quality
peritoneum	UBERON:0002358	87.97	gold quality
cardiac muscle of right atrium	UBERON:0003379	87.72	gold quality
synovial joint	UBERON:0002217	87.70	gold quality
layer of synovial tissue	UBERON:0007616	87.49	gold quality
cortical plate	UBERON:0005343	87.24	gold quality
islet of Langerhans	UBERON:0000006	87.02	gold quality
epithelial cell of pancreas	CL:0000083	86.99	gold quality
upper leg skin	UBERON:0004262	86.77	gold quality
Brodmann (1909) area 46	UBERON:0006483	86.70	gold quality
quadriceps femoris	UBERON:0001377	86.60	gold quality
biceps brachii	UBERON:0001507	86.51	gold quality
vastus lateralis	UBERON:0001379	86.42	gold quality
sural nerve	UBERON:0015488	86.41	gold quality
thoracic mammary gland	UBERON:0005200	86.38	gold quality
secondary oocyte	CL:0000655	86.37	gold quality
skeletal muscle tissue	UBERON:0001134	86.32	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.32	gold quality
muscle tissue	UBERON:0002385	86.25	gold quality
middle temporal gyrus	UBERON:0002771	86.23	gold quality
mammary gland	UBERON:0001911	86.13	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

274 targeting VKORC1L1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4795-3P	100.00	74.62	4024

Literature-anchored findings (GeneRIF, showing 8)

• molecular cloning (PMID:14765194)
• VKORC1L1 does not affect the variability of warfarin dose requirement in a Japanese patient population (PMID:17996924)
• VKORC1L1 is responsible for driving vitamin K-mediated intracellular antioxidation pathways critical to cell survival. (PMID:21367861)
• The involvement of VKORC1L1 in VKOR activity partly explains the low susceptibility of some extrahepatic tissues to vitamin K antagonists. (PMID:23928358)
• a concerted action of the four conserved cysteines of VKORC1L1 for active site regeneration (PMID:24532791)
• This study showed that polymorphisms of EPHX1 and VKORC1L1 could be determinants of stable warfarin doses. (PMID:29054760)
• we have established KO HEK 293T cell lines that express either endogenously VKORC1 or VKORC1L1, and found that VKORC1 is more sensitive to OACs than VKORC1L1, whereas rodenticides apparently inhibit both VKOR enzymes equally (PMID:29581108)
• The disputed loop sequence between the 1st and 2d transmembrane domain of VKOR in the cytoplasm. Using molecular dynamics simulations, a T-shaped stacking interaction between warfarin and Tyr 139, within the proposed TY139A warfarin-binding motif, was seen. Y25, A26, and Y139) were essential for warfarin binding to VKOR, with a reversible dynamic warfarin-binding pocket opening and conformational changes . (PMID:29743176)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	vkorc1l1	ENSDARG00000043644
mus_musculus	Vkorc1l1	ENSMUSG00000066735
rattus_norvegicus		ENSRNOG00000083064

Paralogs (1): VKORC1 (ENSG00000167397)

Protein

Protein identifiers

Vitamin K epoxide reductase complex subunit 1-like protein 1 — Q8N0U8 (reviewed: Q8N0U8)

All UniProt accessions (2): Q8N0U8, A0A3B3ISV4

UniProt curated annotations — full annotation on UniProt →

Function. Involved in vitamin K metabolism. Can reduce inactive vitamin K 2,3-epoxide to active vitamin K, and may contribute to vitamin K-mediated protection against oxidative stress. Plays a role in vitamin K-dependent gamma-carboxylation of Glu residues in target proteins.

Subcellular location. Endoplasmic reticulum membrane.

Activity regulation. Inhibited by warfarin (coumadin). Warfarin locks VKORC1 in both redox states into the closed conformation.

Induction. Up-regulated in response to oxidative stress induced by hydrogen peroxide treatment.

Similarity. Belongs to the VKOR family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N0U8-1	1	yes
Q8N0U8-2	2

RefSeq proteins (2): NP_001271271, NP_775788* (*=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)
• EC 1.17.4.5 — vitamin-K-epoxide reductase (warfarin-insensitive) (BRENDA: 4 organisms, 4 substrates, 11 inhibitors, 0 Km, 0 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 (20 total): topological domain 5, binding site 4, transmembrane region 4, disulfide bond 2, mutagenesis site 2, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N0U8-F1	91.20	0.75

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): 87; 142; 146; 146

Disulfide bonds (2): 50–58, 139–142

Mutagenesis-validated functional residues (2):

Position	Phenotype
50	abolishes enzyme activity in cell-based assays. reduces enzyme activity moderately in assays that regenerate the redox-a
58	abolishes enzyme activity in cell-based assays. reduces enzyme activity moderately in assays that regenerate the redox-a

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6806664	Metabolism of vitamin K

MSigDB gene sets: 156 (showing top): RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, AAAYRNCTG_UNKNOWN, GOBP_KETONE_METABOLIC_PROCESS, MYOD_01, AAAGACA_MIR511, TGACATY_UNKNOWN, GOBP_PEPTIDYL_GLUTAMIC_ACID_MODIFICATION, MYOD_Q6, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, ATCATGA_MIR433, chr7q11, SENESE_HDAC1_TARGETS_UP, PIT1_Q6, GRADE_COLON_AND_RECTAL_CANCER_UP, CP2_01

GO Biological Process (3): peptidyl-glutamic acid carboxylation (GO:0017187), cellular response to oxidative stress (GO:0034599), vitamin K metabolic process (GO:0042373)

GO Molecular Function (5): vitamin-K-epoxide reductase (warfarin-sensitive) activity (GO:0047057), 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 (3): endoplasmic reticulum (GO:0005783), 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
peptidyl-glutamic acid modification	1
protein carboxylation	1
response to oxidative stress	1
cellular response to chemical stress	1
ketone metabolic process	1
oxidoreductase activity, acting on CH or CH2 groups, disulfide as acceptor	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
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

378 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VKORC1L1	TMEM248	Q9NWD8	573
VKORC1L1	GGCX	P38435	544
VKORC1L1	LCN12	Q6JVE5	505
VKORC1L1	GLT8D2	Q9H1C3	430
VKORC1L1	ARHGAP20	Q9P2F6	380
VKORC1L1	IBTK	Q9P2D0	370
VKORC1L1	ZNF469	Q96JG9	370
VKORC1L1	HS3ST3B1	Q9Y662	366
VKORC1L1	LRRK1	Q38SD2	358
VKORC1L1	VWA8	A3KMH1	356
VKORC1L1	TENT5A	Q96IP4	352
VKORC1L1	DGKH	Q86XP1	349
VKORC1L1	VKORC1	Q9BQB6	334
VKORC1L1	GPR15	P49685	322
VKORC1L1	ADAMTS6	Q9UKP5	322

IntAct

144 interactions, top by confidence:

A	B	Type	Score
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
PCYT1A	VKORC1L1	psi-mi:“MI:0915”(physical association)	0.740
VKORC1L1	PCYT1A	psi-mi:“MI:0914”(association)	0.740
VKORC1L1	PCYT1B	psi-mi:“MI:0915”(physical association)	0.560
VKORC1L1	MS4A3	psi-mi:“MI:0915”(physical association)	0.560
AQP6	VKORC1L1	psi-mi:“MI:0915”(physical association)	0.560
VKORC1L1	TMEM80	psi-mi:“MI:0915”(physical association)	0.560
VKORC1L1	CISD2	psi-mi:“MI:0915”(physical association)	0.560
VKORC1L1	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
VKORC1L1	MTIF3	psi-mi:“MI:0915”(physical association)	0.560
MRM1	VKORC1L1	psi-mi:“MI:0915”(physical association)	0.560
VKORC1L1	GPX8	psi-mi:“MI:0915”(physical association)	0.560
GORAB	VKORC1L1	psi-mi:“MI:0915”(physical association)	0.560
VKORC1L1	AGT	psi-mi:“MI:0915”(physical association)	0.560
VKORC1L1	KLKB1	psi-mi:“MI:0915”(physical association)	0.560
VKORC1L1	LPL	psi-mi:“MI:0915”(physical association)	0.560
BRK1	VKORC1L1	psi-mi:“MI:0915”(physical association)	0.560
VKORC1L1	VHL	psi-mi:“MI:0915”(physical association)	0.560
VKORC1L1	CCT2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (144): VKORC1L1 (Affinity Capture-RNA), VKORC1L1 (Affinity Capture-MS), VKORC1L1 (Affinity Capture-MS), VKORC1L1 (Affinity Capture-MS), VKORC1L1 (Affinity Capture-MS), VKORC1L1 (Affinity Capture-MS), VKORC1L1 (Affinity Capture-MS), VKORC1L1 (Affinity Capture-MS), VKORC1L1 (Affinity Capture-MS), VKORC1L1 (Proximity Label-MS), VKORC1L1 (Proximity Label-MS), VKORC1L1 (Proximity Label-MS), VKORC1L1 (Proximity Label-MS), VKORC1L1 (Affinity Capture-MS), VKORC1L1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A1B0GTI8, A6NN92, E9Q9H8, F6RWY9, O18968, O64761, O70610, O75712, O93533, O95377, O95452, P08033, P08034, P08983, P25305, P28230, P28231, P28232, P28233, P36380, P49111, P51916, P70689, P79826, Q02738, Q02739, Q0IIL2, Q13571, Q2KJA5, Q3SZ36, Q3T110, Q3TUD9, Q49LS6, Q4VV71, Q58D78, Q5E9Z5, Q5F410, Q5JW98, Q5REZ0, Q60HF7

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

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
VKORC1L1	“down-regulates quantity”	“vitamin K epoxide”	“chemical modification”
VKORC1L1	“up-regulates quantity”	“vitamin K”	“chemical modification”
“vitamin K epoxide”	“up-regulates activity”	VKORC1L1	“chemical activation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 132 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Class A/1 (Rhodopsin-like receptors)	7	5.6×	5e-03
G alpha (q) signalling events	8	5.0×	5e-03
GPCR ligand binding	7	4.9×	8e-03
Neutrophil degranulation	12	3.0×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
amino acid transport	5	12.6×	9e-03
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	6	10.6×	5e-03
phospholipase C-activating G protein-coupled receptor signaling pathway	9	9.6×	1e-04
positive regulation of cytosolic calcium ion concentration	10	9.4×	1e-04
G protein-coupled receptor signaling pathway	16	4.7×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1100 predictions. Top by Δscore:

Variant	Effect	Δscore
7:65954071:CAGGC:C	acceptor_loss	1.0000
7:65954072:A:AG	acceptor_gain	1.0000
7:65954072:A:T	acceptor_loss	1.0000
7:65954072:AG:A	acceptor_gain	1.0000
7:65954073:G:GA	acceptor_gain	1.0000
7:65954073:GG:G	acceptor_gain	1.0000
7:65954073:GGC:G	acceptor_gain	1.0000
7:65954073:GGCA:G	acceptor_gain	1.0000
7:65954073:GGCAT:G	acceptor_gain	1.0000
7:65954326:TCTC:T	donor_gain	1.0000
7:65873562:CCAGG:C	donor_loss	0.9900
7:65873563:CAG:C	donor_loss	0.9900
7:65873564:AG:A	donor_loss	0.9900
7:65873565:GG:G	donor_loss	0.9900
7:65873566:G:GA	donor_loss	0.9900
7:65873567:T:C	donor_loss	0.9900
7:65946778:A:AG	donor_gain	0.9900
7:65948669:AGATG:A	acceptor_gain	0.9900
7:65948670:GATGG:G	acceptor_gain	0.9900
7:65948778:TTGGT:T	donor_loss	0.9900
7:65948779:TGG:T	donor_loss	0.9900
7:65948780:GGT:G	donor_loss	0.9900
7:65948781:GT:G	donor_loss	0.9900
7:65948782:TAAG:T	donor_loss	0.9900
7:65948783:A:AT	donor_loss	0.9900
7:65948784:AG:A	donor_loss	0.9900
7:65954070:A:AG	acceptor_gain	0.9900
7:65954204:G:GG	donor_gain	0.9900
7:65954295:G:GT	donor_gain	0.9900
7:65873539:G:GT	donor_gain	0.9800

AlphaMissense

1108 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:65873447:G:A	G26R	0.998
7:65873447:G:C	G26R	0.998
7:65954237:C:A	N156K	0.998
7:65954237:C:G	N156K	0.998
7:65873414:G:A	E15K	0.996
7:65873448:G:A	G26E	0.996
7:65948780:G:C	G102R	0.996
7:65954085:A:C	S106R	0.996
7:65954087:C:A	S106R	0.996
7:65954087:C:G	S106R	0.996
7:65954119:C:T	S117F	0.996
7:65954216:C:A	N149K	0.996
7:65954216:C:G	N149K	0.996
7:65954245:G:C	R159P	0.996
7:65954248:T:C	L160P	0.996
7:65954257:T:C	L163S	0.996
7:65873411:T:A	W14R	0.995
7:65873411:T:C	W14R	0.995
7:65873438:T:C	C23R	0.995
7:65948681:G:A	G69R	0.995
7:65948681:G:C	G69R	0.995
7:65948682:G:A	G69E	0.995
7:65948756:T:C	F94L	0.995
7:65948758:T:A	F94L	0.995
7:65948758:T:G	F94L	0.995
7:65954119:C:A	S117Y	0.995
7:65954107:T:C	L113P	0.994
7:65954136:G:A	G123R	0.994
7:65954136:G:C	G123R	0.994
7:65954145:T:G	Y126D	0.994

dbSNP variants (sampled 300 via entrez): RS1000025076 (7:65957814 G>C), RS1000034273 (7:65954187 A>G), RS1000067198 (7:65906700 T>A), RS1000086656 (7:65919174 T>C), RS1000159929 (7:65876708 A>G), RS1000200593 (7:65866464 G>A), RS1000224472 (7:65905392 C>T), RS1000259499 (7:65912454 C>A), RS1000294829 (7:65943046 A>G), RS1000324662 (7:65938224 G>A), RS1000357621 (7:65900437 C>T), RS1000523133 (7:65906312 T>C), RS1000524806 (7:65877859 T>C), RS1000567642 (7:65867510 C>T), RS1000581598 (7:65873712 G>A,C)

Disease associations

OMIM: gene MIM:608838 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001806_8	Corneal structure	4.000000e-09
GCST002201_11	Calcium levels	8.000000e-09
GCST007998_14	Intraocular pressure	2.000000e-09
GCST008058_301	Estimated glomerular filtration rate	3.000000e-11
GCST90002398_380	Neutrophil count	5.000000e-14

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004345	corneal topography
EFO:0004838	calcium measurement
EFO:0004695	intraocular pressure measurement
EFO:0004833	neutrophil count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066256 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4072879	Dosage	3	warfarin

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10950022	VKORC1L1		0.00	0
rs4072879	VKORC1L1	3	2.50	1	warfarin

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.60	Kd	2510	nM	CHEMBL5653589
5.60	ED50	2510	nM	CHEMBL5653589
5.23	Kd	5889	nM	CHEMBL3752910
5.23	ED50	5889	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 5 total; 2 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-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149766: Binding affinity to human VKORC1L1 incubated for 45 mins by Kinobead based pull down assay	kd	2.5098	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149766: Binding affinity to human VKORC1L1 incubated for 45 mins by Kinobead based pull down assay	kd	5.8887	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
vitamin K1 oxide	increases carboxylation, affects reaction, decreases reaction, increases reduction, increases metabolic processing (+1 more)	3
Warfarin	increases reduction, affects binding, decreases activity, decreases reaction, increases metabolic processing (+1 more)	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
coumatetralyl	decreases reaction, increases reduction, decreases activity	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
bromfenacoum	decreases activity, decreases reaction, increases reduction	1
fluindione	decreases activity, decreases reaction, increases reduction	1
bromadiolone	decreases activity, decreases reaction, increases reduction	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-hydroxycoumarin	decreases reaction, increases reduction, decreases activity	1
perfluorooctane sulfonic acid	decreases expression	1
ferulenol	decreases reaction, increases reduction, decreases activity	1
coumachlor	decreases activity, decreases reaction, increases reduction	1
bisphenol B	increases expression	1
abrine	decreases expression	1
bisphenol AF	increases expression	1
Acenocoumarol	decreases reaction, increases reduction, decreases activity	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	affects cotreatment, decreases expression, increases abundance	1
Dicumarol	decreases reaction, increases reduction, decreases activity	1
Coal	decreases expression, increases abundance	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652808	Binding	Binding affinity to human VKORC1L1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TX47	HAP1 VKORC1L1 (-) 1	Cancer cell line	Male
CVCL_TX48	HAP1 VKORC1L1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer