factor VII deficiency

Summary

factor VII deficiency (MONDO:0002244) is a disease caused by F7 (GenCC Definitive), with 2 cohort genes and 8 clinical trials. Top therapeutic interventions include eptacog alfa (activated).

At a glance

• Causal gene: F7 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 117
• Clinical trials: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	factor VII deficiency
Mondo ID	MONDO:0002244
MeSH	D005168
SNOMED CT	37193007
UMLS	C0015503
MedGen	8769
GARD	0023098
Is cancer (heuristic)	no

Also known as: deficiency, stable · F7 deficiency · factor 7 deficiency · factor VII deficiency

Data availability: 117 ClinVar variants · 1 GenCC gene-disease record · 2 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood coagulation disease › coagulation protein disease › factor VII deficiency

Related subtypes (27): factor XIII deficiency, factor X deficiency, thrombophilia due to activated protein C resistance, hypoplasminogenemia, congenital high-molecular-weight kininogen deficiency, congenital factor XII deficiency, alpha-2-plasmin inhibitor deficiency, Tatsumi factor deficiency, East Texas bleeding disorder, inherited prekallikrein deficiency, congenital plasminogen activator inhibitor type 1 deficiency, thrombomodulin-related bleeding disorder, congenital vitamin K-dependent coagulation factors deficiency, hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation, multiple sclerosis-ichthyosis-factor VIII deficiency syndrome, congenital fibrinogen deficiency, combined deficiency of factor V and factor VIII, hemophilia, factor V deficiency, acquired coagulation factor deficiency, von Willebrand disease (hereditary or acquired), factor V short isoforms-related bleeding disorder, factor V amsterdam bleeding disorder, factor V atlanta bleeding disorder, combined deficiency of factor VII and factor X, plasminogen deficiency, type II, dysplasminogenemia

Subtypes (2): congenital factor VII deficiency, acquired factor VII 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

117 retrieved; paginated sample, class counts are floors:

54 uncertain significance, 15 pathogenic, 12 likely pathogenic, 12 pathogenic/likely pathogenic, 10 conflicting classifications of pathogenicity, 6 benign, 4 likely benign, 3 benign/likely benign, 1 pathogenic/likely pathogenic; other

ClinVar	Variant (HGVS)	Gene	Classification	Review
1098445	NM_019616.4(F7):c.394G>T (p.Glu132Ter)	F7	Pathogenic	criteria provided, single submitter
1098448	NM_019616.4(F7):c.1272G>A (p.Trp424Ter)	F7	Pathogenic	criteria provided, single submitter
1163548	NM_019616.4(F7):c.854G>A (p.Arg285His)	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12069	NM_019616.4(F7):c.647G>A (p.Cys216Tyr)	F7	Pathogenic	no assertion criteria provided
12071	NM_019616.4(F7):c.1190C>T (p.Thr397Met)	F7	Pathogenic	criteria provided, single submitter
12073	NM_019616.4(F7):c.283A>G (p.Asn95Asp)	F7	Pathogenic	no assertion criteria provided
12074	NM_019616.4(F7):c.364+1G>C	F7	Pathogenic	no assertion criteria provided
12075	NM_019616.4(F7):c.38T>C (p.Leu13Pro)	F7	Pathogenic	no assertion criteria provided
12076	NM_019616.4(F7):c.995C>T (p.Ala332Val)	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12077	NM_019616.4(F7):c.783_799del (p.Arg262fs)	F7	Pathogenic	no assertion criteria provided
12082	NC_000013.11:g.113105748C>G	F7	Pathogenic	no assertion criteria provided
12084	NM_019616.4(F7):c.297C>A (p.Cys99Ter)	F7	Pathogenic	no assertion criteria provided
12085	NM_019616.4(F7):c.1099T>G (p.Cys367Gly)	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12086	NM_019616.4(F7):c.562C>T (p.Gln188Ter)	F7	Pathogenic	no assertion criteria provided
12087	NM_019616.4(F7):c.187G>A (p.Glu63Lys)	F7	Pathogenic	no assertion criteria provided
12089	NM_019616.4(F7):c.1174G>T (p.Gly392Cys)	F7	Pathogenic	no assertion criteria provided
12090	NM_019616.4(F7):c.917T>C (p.Phe306Ser)	F7	Pathogenic	no assertion criteria provided
265135	NM_019616.4(F7):c.1043G>T (p.Cys348Phe)	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
420159	NM_019616.4(F7):c.1025G>A (p.Arg342Gln)	F7	Pathogenic/Likely pathogenic; other	criteria provided, multiple submitters, no conflicts
420160	NM_019616.4(F7):c.1085C>T (p.Thr362Met)	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
626937	NM_019616.4(F7):c.656C>A (p.Thr219Asn)	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
626945	NM_000131.4(F7):c.-55C>T	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
626999	NM_019616.4(F7):c.1325del (p.Pro442fs)	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
627119	NM_019616.4(F7):c.615+1G>T	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
627178	NM_019616.4(F7):c.413A>G (p.Gln138Arg)	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
627309	NM_019616.4(F7):c.364+1G>A	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
627403	NM_019616.4(F7):c.845C>T (p.Ala282Val)	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1338738	NC_000013.11:g.109179481_114327244del	LOC130010104	Pathogenic	criteria provided, single submitter
1333006	Single allele	COL4A1	Likely pathogenic	criteria provided, single submitter
1098443	NM_019616.4(F7):c.220A>G (p.Arg74Gly)	F7	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 8 · 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
F7	Definitive	Autosomal recessive	congenital factor VII deficiency	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
F7	Orphanet:327	Congenital factor VII deficiency
COL4A1	Orphanet:36383	COL4A1/2-related familial vascular leukoencephalopathy
COL4A1	Orphanet:477749	Pontine autosomal dominant microangiopathy with leukoencephalopathy
COL4A1	Orphanet:481986	Familial schizencephaly
COL4A1	Orphanet:73229	HANAC syndrome
COL4A1	Orphanet:75326	Familial isolated retinal arteriolar tortuosity
COL4A1	Orphanet:899	Walker-Warburg syndrome
COL4A1	Orphanet:99810	Familial porencephaly

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
F7	HGNC:3544	ENSG00000057593	P08709	Coagulation factor VII	gencc,clinvar
COL4A1	HGNC:2202	ENSG00000187498	P02462	Collagen alpha-1(IV) chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
F7	Coagulation factor VII	Initiates the extrinsic pathway of blood coagulation.
COL4A1	Collagen alpha-1(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Protease	1	18.3×	0.108
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
F7	Protease	yes	3.4.21.21	EGF-type_Asp/Asn_hydroxyl_site, GLA_domain, EGF
COL4A1	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
liver	1
right lobe of liver	1
placenta	1
right coronary artery	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
F7	156	tissue_specific	yes	right lobe of liver, liver, buccal mucosa cell
COL4A1	283	ubiquitous	marker	visceral pleura, placenta, right coronary artery

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL4A1	2,909
F7	1,224

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
F7	P08709	114
COL4A1	P02462	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 21. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus	1	634.4×	0.010	F7
Gamma-carboxylation of protein precursors	1	571.0×	0.010	F7
Removal of aminoterminal propeptides from gamma-carboxylated proteins	1	571.0×	0.010	F7
Anchoring fibril formation	1	380.7×	0.010	COL4A1
Scavenging by Class A Receptors	1	300.5×	0.010	COL4A1
Fibronectin matrix formation	1	285.5×	0.010	COL4A1
Crosslinking of collagen fibrils	1	285.5×	0.010	COL4A1
Attachment of bacteria to epithelial cells	1	248.3×	0.010	COL4A1
Initiation of coagulation cascade	1	237.9×	0.010	F7
BMAL1:CLOCK,NPAS2 activates circadian expression	1	211.5×	0.010	F7
Laminin interactions	1	190.3×	0.010	COL4A1
Collagen chain trimerization	1	129.8×	0.012	COL4A1
Signaling by PDGF	1	126.9×	0.012	COL4A1
NCAM1 interactions	1	124.1×	0.012	COL4A1
Regulation of clotting cascade	1	116.5×	0.012	F7
Assembly of collagen fibrils and other multimeric structures	1	100.2×	0.013	COL4A1
Collagen degradation	1	87.8×	0.014	COL4A1
Collagen biosynthesis and modifying enzymes	1	85.2×	0.014	COL4A1
Non-integrin membrane-ECM interactions	1	77.2×	0.014	COL4A1
ECM proteoglycans	1	75.1×	0.014	COL4A1
Integrin cell surface interactions	1	67.2×	0.015	COL4A1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to carbon dioxide	1	8426.0×	0.001	F7
response to Thyroid stimulating hormone	1	8426.0×	0.001	F7
response to astaxanthin	1	8426.0×	0.001	F7
response to thyrotropin-releasing hormone	1	8426.0×	0.001	F7
response to vitamin K	1	2808.7×	0.002	F7
response to genistein	1	2808.7×	0.002	F7
response to thyroxine	1	2808.7×	0.002	F7
renal tubule morphogenesis	1	2106.5×	0.002	COL4A1
positive regulation of platelet-derived growth factor receptor signaling pathway	1	1685.2×	0.002	F7
response to 2,3,7,8-tetrachlorodibenzodioxine	1	1685.2×	0.002	F7
retinal blood vessel morphogenesis	1	1203.7×	0.003	COL4A1
response to cholesterol	1	842.6×	0.003	F7
positive regulation of positive chemotaxis	1	702.2×	0.003	F7
positive regulation of leukocyte chemotaxis	1	648.1×	0.003	F7
collagen-activated tyrosine kinase receptor signaling pathway	1	648.1×	0.003	COL4A1
positive regulation of blood coagulation	1	561.7×	0.004	F7
response to growth hormone	1	561.7×	0.004	F7
blood vessel morphogenesis	1	401.2×	0.005	COL4A1
animal organ regeneration	1	300.9×	0.006	F7
branching involved in blood vessel morphogenesis	1	263.3×	0.006	COL4A1
neuromuscular junction development	1	263.3×	0.006	COL4A1
basement membrane organization	1	255.3×	0.006	COL4A1
positive regulation of TOR signaling	1	247.8×	0.006	F7
response to estrogen	1	172.0×	0.008	F7
cellular response to amino acid stimulus	1	153.2×	0.009	COL4A1
circadian rhythm	1	122.1×	0.011	F7
collagen fibril organization	1	112.3×	0.011	COL4A1
response to estradiol	1	99.1×	0.012	F7
epithelial cell differentiation	1	87.8×	0.013	COL4A1
blood coagulation	1	86.9×	0.013	F7

Therapeutics

Drugs indicated for this disease

1 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Eptacog Alfa (Activated)	Approved (phase 4)

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 2 of 2 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
F7	NIACINAMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
F7	8	4
COL4A1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NIACINAMIDE	4	F7
MELAGATRAN	4	F7
ICOSAPENT	3	F7
GAMOLENIC ACID	3	F7
MILVEXIAN	3	F7
LINOLEIC ACID	2	F7
DIHOMO-GAMMA-LINOLENIC ACID	2	F7
OLEIC ACID	2	F7

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
F7	255	Binding:237, Functional:17, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
F7	3.4.21.21	coagulation factor VIIa

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
F7	255

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

8 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)
NIACINAMIDE	4	F7
MELAGATRAN	4	F7
ICOSAPENT	3	F7
GAMOLENIC ACID	3	F7
MILVEXIAN	3	F7
LINOLEIC ACID	2	F7
DIHOMO-GAMMA-LINOLENIC ACID	2	F7
OLEIC ACID	2	F7

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	F7
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	1	COL4A1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
COL4A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 8.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4
PHASE1	2
PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03079063	PHASE3	COMPLETED	Study Comparing the Pharmacokinetic of Biosimilar Eptacog Alfa With Novoseven®, in Patients With Congenital Factor VII Deficiency
NCT04548791	PHASE1/PHASE2	TERMINATED	Study of Coagulation Factor VIIa Marzeptacog Alfa (Activated) in Subjects With Inherited Bleeding Disorders
NCT06349473	PHASE1	RECRUITING	A Study of Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SR604 in Two Participants Groups (Part A: Healthy Participants, and Part B: Participants With Hemophilia A or Hemophilia B or Factor VII Deficiency)
NCT05651061	PHASE1	COMPLETED	A Phase I of SS109 in Hemophilia A or and B With Inhibitors
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT06938542	Not specified	ENROLLING_BY_INVITATION	Palliative Care Needs of Children With Rare Diseases and Their Families
NCT01269138	Not specified	COMPLETED	Treatment of Inherited Factor VII Deficiency
NCT03372993	Not specified	COMPLETED	Prospective, Non-interventional Study to Evaluate Immunogenicity of AryoSeven

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
EPTACOG ALFA (ACTIVATED)	4	1