VKORC1L1

protein-coding

vitamin K epoxide reductase complex subunit 1 like 1

Gene summary

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]

MANE transcript

NM_173517.6

Inheritance

—

ClinVar variants

U:11B:2

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr7:65,873,074-65,959,563

External References & Databases

Ensembl (ENSG00000196715)

Transcript & Mutation Effects

hg38 • Region Span ~86.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VKORC1L1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 11

not providedTotal: 1

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173517.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense			10 clinvar			10
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	11	2	0	13

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173517.6	RefSeq	NP_775788.2	3	MANE Select
ENST00000360768.5	Ensembl	ENSP00000353998.2	3	MANE Select
NM_001284342.3	RefSeq	NP_001271271.1	2	Standard
ENST00000434382.2	Ensembl	ENSP00000403077.2	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ubiquinone and other terpenoid-quinone biosynthesis - Homo sapiens (human)
Metabolism of fat-soluble vitamins
Metabolism
Metabolism of vitamins and cofactors
Metabolism of vitamin K

Biological Process

peptidyl-glutamic acid carboxylation
cellular response to oxidative stress
vitamin K metabolic process
oxidation-reduction process

Molecular Function

vitamin-K-epoxide reductase (warfarin-sensitive) activity
quinone binding

Cellular Component

endoplasmic reticulum
endoplasmic reticulum membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000360768
Coding exons: 3
Length: 86297
Individuals with no LoFs: 118022
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 118023
p: 0.00000424

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.79	47	96.5	0.487	0.00000525	1093
Missense (PolyPhen)		10	34.992	0.28578		456
Synonymous	0.178	44	45.5	0.966	0.00000279	371
Loss of Function	2.29	0	6.12	0.00	2.59e-7	85

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000093	0.0000093	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. {ECO:0000269|PubMed:21367861, ECO:0000269|PubMed:23928358, ECO:0000269|PubMed:24532791}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.0921
RVIS EVS: 0.01
RVIS percentile EVS: 54.63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium