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.... See more...

Aliases for VKORC1L1 Gene

Aliases for VKORC1L1 Gene

  • Vitamin K Epoxide Reductase Complex Subunit 1 Like 1 2 3 5
  • Vitamin K Epoxide Reductase Complex Subunit 1-Like Protein 1 3 4
  • VKORC1-Like Protein 1 3 4
  • EC 1.17.4.4 4
  • VKORC1L1 5

External Ids for VKORC1L1 Gene

Previous GeneCards Identifiers for VKORC1L1 Gene

  • GC07P064749
  • GC07P064782
  • GC07P064975
  • GC07P065338
  • GC07P061601
  • GC07P065874
  • GC07P065836

Summaries for VKORC1L1 Gene

Entrez Gene Summary for VKORC1L1 Gene

  • 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. [provided by RefSeq, Oct 2016]

GeneCards Summary for VKORC1L1 Gene

VKORC1L1 (Vitamin K Epoxide Reductase Complex Subunit 1 Like 1) is a Protein Coding gene. Diseases associated with VKORC1L1 include Vitamin K Deficiency Bleeding. Among its related pathways are Metabolism of fat-soluble vitamins and Metabolism. Gene Ontology (GO) annotations related to this gene include quinone binding and vitamin-K-epoxide reductase (warfarin-sensitive) activity. An important paralog of this gene is ENSG00000255439.

UniProtKB/Swiss-Prot Summary for VKORC1L1 Gene

  • Involved in vitamin K metabolism. Can reduce inactive vitamin K 2,3-epoxide to active vitamin K (in vitro), 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.

Additional gene information for VKORC1L1 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for VKORC1L1 Gene

Genomics for VKORC1L1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for VKORC1L1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH07J065749 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 635.1 -114.5 -114471 3.4 SP1 GATAD2A PRDM10 RFX1 LEF1 ZNF692 POLR2A BACH1 FOS LARP7 VKORC1L1 CCT6P1 lnc-VKORC1L1-7 piR-41405-076 ENSG00000226824 ENSG00000230189 LINC00174 ENSG00000244657 ENSG00000236529 ENSG00000234500
GH07J065872 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas 635 +7.9 7929 2.6 BACH1 RBFOX2 POLR2A NR2C1 ZNF740 HDAC1 YY1 ZFX NRF1 NONO VKORC1L1 ENSG00000226824 ENSG00000236529 RABGEF1 LINC00174 ZNF117 piR-42491-207 RF00017-6223 piR-50444-427 lnc-VKORC1L1-2
GH07J066653 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 28.3 +789.2 789166 3.9 CREB1 GATAD2A HNRNPL TEAD4 PRDM10 ZNF629 TFE3 IKZF1 NFKBIZ ZNF692 ENSG00000226824 RABGEF1 LOC100996437 ENSG00000229180 VKORC1L1 ENSG00000237310 ENSG00000244657 ENSG00000230189 CRCP GUSB
GH07J066625 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 28.4 +763.1 763081 6.6 SP1 CREB1 HNRNPL ATF7 ZNF629 RFX1 IKZF1 POLR2A BACH1 FOS KCTD7 ENSG00000284461 MN298404 ENSG00000226824 RABGEF1 VKORC1L1 ENSG00000237310 CCT6P1 RF00017-6229
GH07J066680 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 28.6 +816.9 816936 3.8 CREB1 HNRNPL PRDM10 ZNF629 LEF1 IKZF1 POLR2A TARDBP ZHX2 JUND RABGEF1 lnc-KCTD7-1 ENSG00000226824 VKORC1L1 piR-37750-008 LOC100996437 ENSG00000284461 RF00017-6229 TMEM248
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around VKORC1L1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for VKORC1L1

Top Transcription factor binding sites by QIAGEN in the VKORC1L1 gene promoter:
  • C/EBPalpha
  • Cart-1
  • CHOP-10
  • E47
  • FAC1
  • HNF-3beta
  • HNF-4alpha1
  • Pax-5
  • Spz1
  • Tal-1

Genomic Locations for VKORC1L1 Gene

Genomic Locations for VKORC1L1 Gene
chr7:65,865,772-65,959,563
(GRCh38/hg38)
Size:
93,792 bases
Orientation:
Plus strand
chr7:65,338,254-65,424,550
(GRCh37/hg19)
Size:
86,297 bases
Orientation:
Plus strand

Genomic View for VKORC1L1 Gene

Genes around VKORC1L1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
VKORC1L1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for VKORC1L1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for VKORC1L1 Gene

Proteins for VKORC1L1 Gene

  • Protein details for VKORC1L1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8N0U8-VKORL_HUMAN
    Recommended name:
    Vitamin K epoxide reductase complex subunit 1-like protein 1
    Protein Accession:
    Q8N0U8
    Secondary Accessions:
    • B4E222
    • E7ETM5
    • Q6AHW9
    • Q6TEK6

    Protein attributes for VKORC1L1 Gene

    Size:
    176 amino acids
    Molecular mass:
    19836 Da
    Quaternary structure:
    No Data Available
    Miscellaneous:
    • The location of two cysteine active-site residues within a proposed transmembrane is consistent both with the known hydrophobic environment of the thiol redox site of the enzyme and with the lipophilicity of vitamin K and warfarin (coumadin).

    Alternative splice isoforms for VKORC1L1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for VKORC1L1 Gene

Post-translational modifications for VKORC1L1 Gene

  • Ubiquitination at Lys57 and Lys168
  • Modification sites at PhosphoSitePlus

Other Protein References for VKORC1L1 Gene

No data available for DME Specific Peptides for VKORC1L1 Gene

Domains & Families for VKORC1L1 Gene

Gene Families for VKORC1L1 Gene

Human Protein Atlas (HPA):
  • Enzymes
  • FDA approved drug targets
  • Predicted membrane proteins

Protein Domains for VKORC1L1 Gene

InterPro:
Blocks:
  • Vitamin K epoxide reductase
ProtoNet:

Suggested Antigen Peptide Sequences for VKORC1L1 Gene

GenScript: Design optimal peptide antigens:
  • Vitamin K epoxide reductase complex subunit 1-like protein 1 (VKORL_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8N0U8

UniProtKB/Swiss-Prot:

VKORL_HUMAN :
  • Belongs to the VKOR family.
Family:
  • Belongs to the VKOR family.
genes like me logo Genes that share domains with VKORC1L1: view

Function for VKORC1L1 Gene

Molecular function for VKORC1L1 Gene

UniProtKB/Swiss-Prot Function:
Involved in vitamin K metabolism. Can reduce inactive vitamin K 2,3-epoxide to active vitamin K (in vitro), 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.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=[protein]-disulfide + H2O + phylloquinone = 2,3-epoxyphylloquinone + [protein]-dithiol; Xref=Rhea:RHEA:13817, Rhea:RHEA-COMP:10593, Rhea:RHEA-COMP:10594, ChEBI:CHEBI:15377, ChEBI:CHEBI:15759, ChEBI:CHEBI:18067, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058; EC=1.17.4.4; Evidence={ECO:0000269|PubMed:21367861, ECO:0000269|PubMed:23928358, ECO:0000269|PubMed:24532791};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=[protein]-disulfide + phylloquinol = [protein]-dithiol + phylloquinone; Xref=Rhea:RHEA:57744, Rhea:RHEA-COMP:10593, Rhea:RHEA-COMP:10594, ChEBI:CHEBI:18067, ChEBI:CHEBI:28433, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058; EC=1.17.4.4; Evidence={ECO:0000269|PubMed:21367861, ECO:0000269|PubMed:23928358, ECO:0000269|PubMed:24532791};.
UniProtKB/Swiss-Prot Induction:
Up-regulated in response to oxidative stress induced by hydrogen peroxide treatment.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by warfarin (coumadin).

Enzyme Numbers (IUBMB) for VKORC1L1 Gene

Phenotypes From GWAS Catalog for VKORC1L1 Gene

Gene Ontology (GO) - Molecular Function for VKORC1L1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016491 oxidoreductase activity IEA --
GO:0047057 vitamin-K-epoxide reductase (warfarin-sensitive) activity IDA 21367861
GO:0048038 quinone binding IEA --
genes like me logo Genes that share ontologies with VKORC1L1: view

Phenotypes for VKORC1L1 Gene

genes like me logo Genes that share phenotypes with VKORC1L1: view

Animal Models for VKORC1L1 Gene

MGI Knock Outs for VKORC1L1:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for VKORC1L1

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for VKORC1L1 Gene

Localization for VKORC1L1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for VKORC1L1 Gene

Endoplasmic reticulum membrane. Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for VKORC1L1 gene
Compartment Confidence
endoplasmic reticulum 5
plasma membrane 3
extracellular 1
mitochondrion 1
nucleus 1
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Endoplasmic reticulum (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for VKORC1L1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum IEA,IDA --
GO:0005789 endoplasmic reticulum membrane TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with VKORC1L1: view

Pathways & Interactions for VKORC1L1 Gene

genes like me logo Genes that share pathways with VKORC1L1: view

Pathways by source for VKORC1L1 Gene

Gene Ontology (GO) - Biological Process for VKORC1L1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0017187 peptidyl-glutamic acid carboxylation IMP 24532791
GO:0034599 cellular response to oxidative stress IMP 21367861
GO:0042373 vitamin K metabolic process TAS --
GO:0055114 oxidation-reduction process IEA --
genes like me logo Genes that share ontologies with VKORC1L1: view

No data available for SIGNOR curated interactions for VKORC1L1 Gene

Drugs & Compounds for VKORC1L1 Gene

(2) Drugs for VKORC1L1 Gene - From: DrugBank, PharmGKB, DGIdb, and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Menadione Approved Nutra Target, cofactor, inhibitor 327
Warfarin Approved Pharma inhibitor 609
genes like me logo Genes that share compounds with VKORC1L1: view

Transcripts for VKORC1L1 Gene

mRNA/cDNA for VKORC1L1 Gene

2 REFSEQ mRNAs :
16 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for VKORC1L1

Alternative Splicing Database (ASD) splice patterns (SP) for VKORC1L1 Gene

No ASD Table

Relevant External Links for VKORC1L1 Gene

GeneLoc Exon Structure for
VKORC1L1

Expression for VKORC1L1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for VKORC1L1 Gene

Protein differential expression in normal tissues from HIPED for VKORC1L1 Gene

This gene is overexpressed in Adipocyte (13.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for VKORC1L1 Gene



Protein tissue co-expression partners for VKORC1L1 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for VKORC1L1

SOURCE GeneReport for Unigene cluster for VKORC1L1 Gene:

Hs.427232

Evidence on tissue expression from TISSUES for VKORC1L1 Gene

  • Kidney(4.4)
  • Nervous system(2.6)
  • Liver(2.2)
genes like me logo Genes that share expression patterns with VKORC1L1: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for VKORC1L1 Gene

Orthologs for VKORC1L1 Gene

This gene was present in the common ancestor of animals.

Orthologs for VKORC1L1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia VKORC1L1 30
  • 100 (n)
Dog
(Canis familiaris)
Mammalia VKORC1L1 30 31
  • 94.32 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Vkorc1l1 30
  • 92.99 (n)
Mouse
(Mus musculus)
Mammalia Vkorc1l1 30 17 31
  • 92.05 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia VKORC1L1 30 31
  • 91.86 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia VKORC1L1 31
  • 82 (a)
OneToOne
Chicken
(Gallus gallus)
Aves VKORC1L1 30 31
  • 81.82 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia VKORC1L1 31
  • 57 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia vkorc1l1 30
  • 78.1 (n)
Zebrafish
(Danio rerio)
Actinopterygii vkorc1l1 30 31
  • 74.29 (n)
OneToOne
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.12700 30
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000543 30
  • 54.4 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta Vkor 31
  • 26 (a)
OneToMany
Species where no ortholog for VKORC1L1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for VKORC1L1 Gene

ENSEMBL:
Gene Tree for VKORC1L1 (if available)
TreeFam:
Gene Tree for VKORC1L1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for VKORC1L1: view image

Paralogs for VKORC1L1 Gene

Paralogs for VKORC1L1 Gene

(1) SIMAP similar genes for VKORC1L1 Gene using alignment to 2 proteins:

  • VKORL_HUMAN
  • E7ETM5_HUMAN

Pseudogenes.org Pseudogenes for VKORC1L1 Gene

genes like me logo Genes that share paralogs with VKORC1L1: view

Variants for VKORC1L1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for VKORC1L1 Gene

SNP ID Clinical significance and condition Chr 07 pos Variation AA Info Type
rs193921078 Uncertain Significance: Malignant tumor of prostate 65,954,262(+) G/T MISSENSE_VARIANT,NONSENSE

Additional dbSNP identifiers (rs#s) for VKORC1L1 Gene

Structural Variations from Database of Genomic Variants (DGV) for VKORC1L1 Gene

Variant ID Type Subtype PubMed ID
dgv6444n100 CNV gain 25217958
esv21527 CNV gain 19812545
esv2664145 CNV deletion 23128226
esv2759534 CNV gain+loss 17122850
esv2761079 CNV gain+loss 21179565
esv2764020 CNV gain+loss 21179565
esv3613491 CNV loss 21293372
esv3613492 CNV gain 21293372
esv3613493 CNV gain 21293372
nsv1020622 CNV gain 25217958
nsv1028971 CNV gain 25217958
nsv1029800 CNV loss 25217958
nsv1076916 CNV deletion 25765185
nsv1119125 CNV deletion 24896259
nsv1137585 CNV deletion 24896259
nsv966829 CNV duplication 23825009
nsv966830 CNV duplication 23825009

Variation tolerance for VKORC1L1 Gene

Residual Variation Intolerance Score: 48.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.79; 83.35% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for VKORC1L1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
VKORC1L1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for VKORC1L1 Gene

Disorders for VKORC1L1 Gene

MalaCards: The human disease database

(1) MalaCards diseases for VKORC1L1 Gene - From: DISEASES

Disorder Aliases PubMed IDs
vitamin k deficiency bleeding
  • deficiency of vitamin k
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for VKORC1L1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with VKORC1L1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for VKORC1L1 Gene

Publications for VKORC1L1 Gene

  1. VKORC1L1, an enzyme rescuing the vitamin K 2,3-epoxide reductase activity in some extrahepatic tissues during anticoagulation therapy. (PMID: 23928358) Hammed A … Lattard V (The Journal of biological chemistry 2013) 2 3 4
  2. Conserved loop cysteines of vitamin K epoxide reductase complex subunit 1-like 1 (VKORC1L1) are involved in its active site regeneration. (PMID: 24532791) Tie JK … Stafford DW (The Journal of biological chemistry 2014) 3 4
  3. Human vitamin K 2,3-epoxide reductase complex subunit 1-like 1 (VKORC1L1) mediates vitamin K-dependent intracellular antioxidant function. (PMID: 21367861) Westhofen P … Oldenburg J (The Journal of biological chemistry 2011) 3 4
  4. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41
  5. No association between vitamin K epoxide reductase complex subunit 1-like 1 (VKORC1L1) and the variability of warfarin dose requirement in a Japanese patient population. (PMID: 17996924) Yin T … Miyata T (Thrombosis research 2008) 3 23

Products for VKORC1L1 Gene

  • Biorbyt antibodies for VKORC1L1

Sources for VKORC1L1 Gene