VKORC1L1 Gene - Vitamin K Epoxide Reductase Complex Subunit 1-Like 1
<table class="infobox infobox-gene">
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<th class="infobox-header" colspan="2">VKORC1L1 — Vitamin K Epoxide Reductase Complex Subunit 1-Like 1</th>
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<td class="label">Symbol</td>
<td><strong>VKORC1L1</strong></td>
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<td class="label">Full Name</td>
<td>Vitamin K Epoxide Reductase Complex Subunit 1-Like 1</td>
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<td class="label">Chromosome</td>
<td>7q11.22</td>
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<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/89439" target="_blank">89439</a></td>
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<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000137868" target="_blank">ENSG00000137868</a></td>
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<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/Q8N4U2" target="_blank">Q8N4U2</a></td>
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<td class="label">Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers)</td>
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<td class="label">Expression</td>
<td>Brain, Liver, Lung, Heart</td>
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<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/colorectal-cancer" style="color:#ef9a9a">Colorectal Cancer</a>, <a href="/wiki/tumor" style="color:#ef9a9a">Tumor</a></td>
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<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">15 edges</a></td>
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</table>
VKORC1L1 — Vitamin K Epoxide Reductase Complex Subunit 1-Like 1
Introduction
VKORC1L1 (Vitamin K Epoxide Reductase Complex Subunit 1-Like 1) is a gene located on chromosome 7q11.22 that encodes a vitamin K epoxide reductase enzyme. While structurally similar to the canonical VKORC1 gene involved in warfarin sensitivity, VKORC1L1 has distinct tissue distribution and physiological functions[^ORC1L1]. VK1 has been implicated in Alzheimer's disease risk through genome-wide association studies (GWAS), highlighting the potential role of vitamin K metabolism in neurodegenerative processes[@protein][@therapeutic].
Overview
Mermaid diagram (expand to render)
| Property | Value |
|----------|-------|
| Location | 7q11.22 |
| Protein | VKORC1L1 (~373 aa) |
| Primary function | Vitamin K metabolism |
| Tissue expression | Brain, Liver, Lung, Heart |
Normal Physiological Functions
VKORC1L1 plays a crucial role in the vitamin K cycle:
- Vitamin K recycling: Catalyzes the reduction of vitamin K epoxide to vitamin K hydroquinone, the active form
- Gamma-carboxylation: Supports the gamma-carboxylation of Gla-containing proteins including clotting factors, osteocalcin, and matrix Gla protein
- Oxidative stress response: The vitamin K cycle is linked to cellular antioxidant systems through NAD(P)H-dependent reductases[@gene]
Tissue-Specific Functions
- Liver: Contributes to coagulation factor synthesis
- Brain: Expressed in [neurons](/entities/neurons) and glial cells; vitamin K is involved in myelin formation and neuronal survival
- Cardiovascular system: Supports vascular calcification regulation through matrix Gla protein
Disease Associations
Alzheimer's Disease (AD)
VKORC1L1 variants have been associated with AD risk in GWAS studies[@protein][@therapeutic]:
- Genetic association: Variants in the VKORC1L1 region show nominal association with AD in meta-analyses
- Potential mechanisms:
- Vitamin K's role in brain lipid metabolism and myelin maintenance
- Involvement in sphingolipid metabolism, which is altered in AD
- Potential effects on neuronal survival through gas6/TAM receptor signaling[@mutations]
Other Neurological Conditions
- Parkinson's disease: Preliminary studies suggest potential involvement of vitamin K pathway genes
- Multiple sclerosis: Vitamin K supplementation has been explored as a potential therapeutic approach
Molecular Interactions
VKORC1L1 interacts with several key proteins and pathways:
- VKORC1: Paralogous gene with overlapping and distinct functions
- Gamma-glutamyl carboxylase (GGCX): Works in concert for protein carboxylation
- Warfarin: Both VKORC1 and VKORC1L1 are sensitive to warfarin inhibition
- Sphingolipid metabolism pathway: Genetic evidence suggests shared mechanisms with AD
Therapeutic Implications
Vitamin K as a Potential Therapeutic
- Observational studies: Lower vitamin K levels have been associated with cognitive decline
- Preclinical evidence: Vitamin K supplementation may protect against neuronal death
- Clinical trials: Ongoing studies evaluating vitamin K supplementation in MCI and AD
Drug Interactions
- Warfarin: Both VKORC1 and VKORC1L1 are inhibited by warfarin
- Vitamin K antagonists: Important consideration for patients on anticoagulant therapy
Key Publications
[@gene]: Tie JK, Stafford AR, Zhou Y, et al. Functional characterization of vitamin K epoxide reductase complex subunit 1-like 1 (VKORC1L1). J Thromb Haemost. 2015;13(7):1264-1273. PMID: 25903649(https://pubmed.ncbi.nlm.nih.gov/25903649/)
[@protein]: Lambert JC, Ibrahim-Verbaas CA, Harold D, et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat Genet. 2013;45(12):1452-1458. PMID: 24162737(https://pubmed.ncbi.nlm.nih.gov/24162737/)
[@therapeutic]: Karch CM, Goate AM. Alzheimer's disease risk genes and mechanisms of disease pathogenesis. Biol Psychiatry. 2015;77(1):43-51. PMID: 25195381(https://pubmed.ncbi.nlm.nih.gov/25195381/)
[@mutations]: Bellettato CM, Scarpa M. Possible involvement of gas6/TAM system in the pathogenesis of Alzheimer's disease. J Alzheimers Dis. 2018;61(4):1457-1469. PMID: 29332053(https://pubmed.ncbi.nlm.nih.gov/29332053/)
See Also
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Vitamin K Metabolism](/mechanisms/vitamin-k-metabolism)
- [VKORC1 Gene](/genes/vkorc1)
Background
The study of Vkorc1L1 Gene Vitamin K Epoxide Reductase Complex Subunit 1 Like 1 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
External Links
- [NCBI Gene: VKORC1L1](https://www.ncbi.nlm.nih.gov/gene/89439)
- [UniProt: Q8N4U2](https://www.uniprot.org/uniprot/Q8N4U2)
- [Ensembl: ENSG00000137868](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000137868)
References
Unknown, Gene function and disease associations - PubMed (n.d.)
Unknown, Protein structure and mechanism studies - PubMed (n.d.)
Unknown, Therapeutic targeting potential - PubMed (n.d.)
Unknown, Mutations and disease variants - PubMed (n.d.)
Unknown, Expression and regulation in nervous system - PubMed (n.d.)Pathway Diagram
The following diagram shows the key molecular relationships involving VKORC1L1 Gene - Vitamin K Epoxide Reductase Complex Subunit 1-Like 1 discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)