VKORC1
vitamin K epoxide reductase complex subunit 1
Basic information
Region (hg38): 16:31090842-31095980
Previous symbols: [ "VKCFD2" ]
Links
Phenotypes
GenCC
Source:
- vitamin K-dependent clotting factors, combined deficiency of, type 1 (Supportive), mode of inheritance: AR
- vitamin K-dependent clotting factors, combined deficiency of, type 2 (Limited), mode of inheritance: Unknown
- vitamin K-dependent clotting factors, combined deficiency of, type 2 (Moderate), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Vitamin K-dependent clotting factors, combined deficiency of, 2; Drug metabolism, VKORC1-related | AD/AR | Hematologic; Pharmacogenomic | Individuals may present with severe bleeding episodes (including, for example, fatal neonatal intracranial hemorrhage), and oral administration of vitamin K typically reverses bleeding tendency; Variants may have pharmacogenomic relevance (related to Drug metabolism, VKORC1-related) in regards to selection and dosing of medications (including warfarin) | Hematologic | 11154138; 12384421; 14765194; 15930419; 15947090; 15888487; 16611310; 17653141; 18466099; 18535201; 18855533; 19207028; 19228618; 19300499; 20203262; 20833980; 19794411; 21148049; 22431865; 22528326; 23215886; 23276529; 23277416; 23279643; 23677510 |
ClinVar
This is a list of variants' phenotypes submitted to
- Vitamin_K-dependent_clotting_factors,_combined_deficiency_of,_type_2 (18 variants)
- not_provided (9 variants)
- Warfarin_response (6 variants)
- VKORC1-related_disorder (6 variants)
- not_specified (6 variants)
- Thrombus (1 variants)
- warfarin_response_-_Dosage (1 variants)
- Hereditary_combined_deficiency_of_vitamin_K-dependent_clotting_factors (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the VKORC1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024006.6. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 9 | |||||
| missense | 12 | 19 | ||||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 3 | 2 | 19 | 2 | 3 |
Highest pathogenic variant AF is 0.000058264366
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| VKORC1 | protein_coding | protein_coding | ENST00000394975 | 3 | 5139 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.162 | 0.780 | 125691 | 0 | 11 | 125702 | 0.0000438 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.305 | 85 | 93.3 | 0.911 | 0.00000503 | 1021 |
| Missense in Polyphen | 28 | 36.219 | 0.77307 | 434 | ||
| Synonymous | 0.537 | 38 | 42.5 | 0.895 | 0.00000227 | 347 |
| Loss of Function | 1.55 | 2 | 6.16 | 0.325 | 2.65e-7 | 63 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000303 | 0.000297 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000179 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- 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. {ECO:0000269|PubMed:14765194, ECO:0000269|PubMed:14765195, ECO:0000269|PubMed:15879509, ECO:0000269|PubMed:16270630, ECO:0000269|PubMed:20978134, ECO:0000269|PubMed:22923610}.;
- Disease
- DISEASE: 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. {ECO:0000269|PubMed:14765194, ECO:0000269|PubMed:16270630}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:14765194, ECO:0000269|PubMed:20946155}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Ubiquinone and other terpenoid-quinone biosynthesis - Homo sapiens (human);Warfarin Pathway, Pharmacodynamics;Aminocaproic Acid Action Pathway;Tranexamic Acid Action Pathway;Urokinase Action Pathway;Reteplase Action Pathway;Streptokinase Action Pathway;Tenecteplase Action Pathway;Alteplase Action Pathway;Anistreplase Action Pathway;Aprotinin Action Pathway;Phenindione Action Pathway;Dicoumarol Action Pathway;Warfarin Action Pathway;Acenocoumarol Action Pathway;Vitamin K Metabolism;Coagulation ;Bivalirudin Action Pathway;Argatroban Action Pathway;Ardeparin Action Pathway;Heparin Action Pathway;Fondaparinux Action Pathway;Enoxaparin Action Pathway;Phenprocoumon Action Pathway;Dicumarol Action Pathway;Ximelagatran Action Pathway;Lepirudin Action Pathway;Metabolism of fat-soluble vitamins;Metabolism;Metabolism of vitamins and cofactors;Metabolism of vitamin K
(Consensus)
Intolerance Scores
- loftool
- rvis_EVS
- 0.19
- rvis_percentile_EVS
- 66.57
Haploinsufficiency Scores
- pHI
- 0.177
- hipred
- N
- hipred_score
- 0.139
- ghis
- 0.458
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.979
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Vkorc1
- Phenotype
- homeostasis/metabolism phenotype; skeleton phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan);
Gene ontology
- Biological process
- blood coagulation;response to organonitrogen compound;response to organic cyclic compound;drug metabolic process;peptidyl-glutamic acid carboxylation;regulation of blood coagulation;vitamin K metabolic process;response to antibiotic;oxidation-reduction process;bone development
- Cellular component
- endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane
- Molecular function
- vitamin-K-epoxide reductase (warfarin-sensitive) activity;vitamin-K-epoxide reductase (warfarin-insensitive) activity;quinone binding