VKORC1L1

Chr 7

vitamin K epoxide reductase complex subunit 1L1

NCBI Gene: 154807ENSG00000196715UniProt: Q8N0U8

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]

0
Active trials
15
Pathogenic / LP
33
ClinVar variants
2
Pubs (1 yr)
1.8
Missense Z
0.49
LOEUF
Clinical Summary— VKORC1L1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.84) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 13 VUS of 33 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.844
Z-score 2.29
OE 0.00 (0.00–0.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.79Z-score
OE missense 0.49 (0.39–0.62)
47 obs / 96.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.49)
0≤0.351.4
Missense OE0.49 (0.39–0.62)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 0 / 6.1Missense obs/exp: 47 / 96.5Syn Z: 0.18
DN
DN
0.6161th %ile
GOF
0.5170th %ile
LOF
0.3550th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

33 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic1
VUS13
Likely Benign5
14
Pathogenic
1
Likely Pathogenic
13
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
1
0
1
VUS
0
11
2
0
13
Likely Benign
0
1
3
1
5
Benign
0
0
0
0
0
Total01220133

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

VKORC1L1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
VKORC1L1 Downregulation Induced Vitamin K Cycle Disorder Exacerbates Neuronal Ferroptosis After Spinal Cord Injury.
Tan M et al.·Mol Neurobiol
2026
Regulation of VKORC1L1 is critical for p53-mediated tumor suppression through vitamin K metabolism.
Yang X et al.·Cell Metab
2023
Mechanism of VKORC1 and VKORC1L1 signaling in the effects of sodium dehydroacetate on coagulation factors in rat hepatocytes.
Zhou Z et al.·Toxicol In Vitro
2023Functional
Vitamin K Epoxide Reductase Complex Subunit 1-Like 1 (VKORC1L1) Inhibition Induces a Proliferative and Pro-inflammatory Vascular Smooth Muscle Cell Phenotype.
Aksoy A et al.·Front Cardiovasc Med
2021Open Access
Avian interspecific differences in VKOR activity and inhibition: Insights from amino acid sequence and mRNA expression ratio of VKORC1 and VKORC1L1.
Nakayama SMM et al.·Comp Biochem Physiol C Toxicol Pharmacol
2020
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients