vitamin K-dependent clotting factors, combined deficiency of, type 2
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Also known as congenital vitamin K-dependent coagulation factors combined deficiency caused by mutation in VKORC1vitamin K-dependent clotting factors, combined deficiency of, 2VKCFD2VKORC1 congenital vitamin K-dependent coagulation factors combined deficiency
Summary
vitamin K-dependent clotting factors, combined deficiency of, type 2 (MONDO:0011837) is a disease caused by VKORC1 (GenCC Strong), with 1 cohort gene.
At a glance
- Causal gene: VKORC1 (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 24
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | vitamin K-dependent clotting factors, combined deficiency of, type 2 |
| Mondo ID | MONDO:0011837 |
| MeSH | C564393 |
| OMIM | 607473 |
| DOID | DOID:0112174 |
| UMLS | C1843832 |
| MedGen | 334505 |
| GARD | 0018196 |
| Is cancer (heuristic) | no |
Also known as: congenital vitamin K-dependent coagulation factors combined deficiency caused by mutation in VKORC1 · vitamin K-dependent clotting factors, combined deficiency of, 2 · vitamin K-dependent clotting factors, combined deficiency of, type 2 · VKCFD2 · VKORC1 congenital vitamin K-dependent coagulation factors combined deficiency
Data availability: 24 ClinVar variants · 2 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood coagulation disease › coagulation protein disease › congenital vitamin K-dependent coagulation factors deficiency › vitamin K-dependent clotting factors, combined deficiency of, type 2
Related subtypes (4): congenital factor VII deficiency, congenital factor X deficiency, vitamin K-dependent clotting factors, combined deficiency of, type 1, congenital prothrombin deficiency
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
24 retrieved; paginated sample, class counts are floors:
14 uncertain significance, 3 benign, 2 drug response, 2 likely benign, 1 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 benign/likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 2206 | NM_024006.6(VKORC1):c.292C>T (p.Arg98Trp) | VKORC1 | Likely pathogenic | criteria provided, single submitter |
| 2212 | NM_024006.6(VKORC1):c.106G>T (p.Asp36Tyr) | VKORC1 | drug response | reviewed by expert panel |
| 226016 | NM_024006.6(VKORC1):c.*134G>A | VKORC1 | drug response | reviewed by expert panel |
| 692018 | NM_024006.6(VKORC1):c.196G>A (p.Val66Met) | VKORC1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 318973 | NM_024006.6(VKORC1):c.*245G>A | VKORC1 | Uncertain significance | criteria provided, single submitter |
| 318976 | NM_024006.6(VKORC1):c.267A>T (p.Thr89=) | VKORC1 | Uncertain significance | criteria provided, single submitter |
| 4277943 | NM_024006.6(VKORC1):c.230A>G (p.Asn77Ser) | VKORC1 | Uncertain significance | criteria provided, single submitter |
| 884452 | NM_024006.6(VKORC1):c.117C>T (p.Tyr39=) | VKORC1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 884453 | NM_024006.6(VKORC1):c.54G>T (p.Thr18=) | VKORC1 | Uncertain significance | criteria provided, single submitter |
| 884454 | NM_024006.6(VKORC1):c.-2T>C | VKORC1 | Uncertain significance | criteria provided, single submitter |
| 884455 | NM_024006.6(VKORC1):c.-45G>A | VKORC1 | Uncertain significance | criteria provided, single submitter |
| 887421 | NM_024006.6(VKORC1):c.*172T>A | VKORC1 | Uncertain significance | criteria provided, single submitter |
| 887422 | NM_024006.6(VKORC1):c.*10C>G | VKORC1 | Uncertain significance | criteria provided, single submitter |
| 887423 | NM_024006.6(VKORC1):c.447T>C (p.Ser149=) | VKORC1 | Uncertain significance | criteria provided, single submitter |
| 887424 | NM_024006.6(VKORC1):c.379G>A (p.Val127Met) | VKORC1 | Uncertain significance | criteria provided, single submitter |
| 887599 | NM_024006.6(VKORC1):c.342C>G (p.Leu114=) | VKORC1 | Uncertain significance | criteria provided, single submitter |
| 887601 | NM_024006.6(VKORC1):c.202C>T (p.His68Tyr) | VKORC1 | Uncertain significance | criteria provided, single submitter |
| 887602 | NM_024006.6(VKORC1):c.173+11G>T | VKORC1 | Uncertain significance | criteria provided, single submitter |
| 318975 | NM_024006.6(VKORC1):c.358C>T (p.Leu120=) | VKORC1 | Benign | criteria provided, multiple submitters, no conflicts |
| 318977 | NM_024006.6(VKORC1):c.36G>A (p.Arg12=) | VKORC1 | Benign | criteria provided, multiple submitters, no conflicts |
| 791061 | NM_024006.6(VKORC1):c.129C>T (p.Cys43=) | VKORC1 | Benign/Likely benign | criteria provided, multiple submitters, no conflicts |
| 887420 | NM_024006.6(VKORC1):c.*243G>A | VKORC1 | Likely benign | criteria provided, single submitter |
| 887598 | NM_024006.6(VKORC1):c.352G>C (p.Val118Leu) | VKORC1 | Likely benign | criteria provided, single submitter |
| 887600 | NM_024006.6(VKORC1):c.203A>G (p.His68Arg) | VKORC1 | Benign | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| VKORC1 | Strong | Autosomal recessive | vitamin K-dependent clotting factors, combined deficiency of, type 2 | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| VKORC1 | Orphanet:98434 | Hereditary combined deficiency of vitamin K-dependent clotting factors |
Cohort genes → proteins
1 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 1 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| VKORC1 | HGNC:23663 | ENSG00000167397 | Q9BQB6 | Vitamin K epoxide reductase complex subunit 1 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| VKORC1 | Vitamin K epoxide reductase complex subunit 1 | Involved in vitamin K metabolism. |
Protein-family classification
Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Enzyme (other) | 1 | 12.0× | 0.083 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| VKORC1 | Enzyme (other) | yes | 1.17.4.4 | VKOR, VKOR_sf, VKORC1/VKORC1L1 |
Expression context
Cohort genes with no expression data: 0.
1 cohort gene are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 1 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| right lobe of liver | 1 |
| stromal cell of endometrium | 1 |
| thoracic aorta | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| VKORC1 | 134 | ubiquitous | marker | stromal cell of endometrium, right lobe of liver, thoracic aorta |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| VKORC1 | 1,009 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| VKORC1 | Q9BQB6 | 6 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).
Pathways by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Metabolism of vitamin K | 1 | 3806.7× | 3e-04 | VKORC1 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| peptidyl-glutamic acid carboxylation | 1 | 8426.0× | 7e-04 | VKORC1 |
| positive regulation of coagulation | 1 | 2808.7× | 9e-04 | VKORC1 |
| vitamin K metabolic process | 1 | 2106.5× | 9e-04 | VKORC1 |
| bone development | 1 | 276.3× | 0.005 | VKORC1 |
| blood coagulation | 1 | 173.7× | 0.007 | VKORC1 |
| xenobiotic metabolic process | 1 | 149.1× | 0.007 | VKORC1 |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0
Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|---|
| VKORC1 | WARFARIN |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| VKORC1 | 1 | 4 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| WARFARIN | 4 | VKORC1 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| VKORC1 | 3 | Binding:3 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| VKORC1 | 1.17.4.4 | vitamin-K-epoxide reductase (warfarin-sensitive) |
Pharmacogenomics
Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 1.
Cohort genes with a CPIC/DPWG dosing guideline
| Symbol | CPIC guidelines |
|---|---|
| VKORC1 | 1 |
Chemical tractability of cohort targets
1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| WARFARIN | 4 | VKORC1 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | VKORC1 |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 0 |
Undrugged target profiles
0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: VKORC1