congenital factor VII deficiency

Summary

congenital factor VII deficiency (MONDO:0009211) is a disease caused by F7 (GenCC Definitive), with 1 cohort gene and 1 clinical trial. Top therapeutic interventions include sutacimig.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: F7 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 101
• Phenotypes (HPO): 12
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.33	Europe	Validated

Signs & symptoms

Clinical features (HPO)

12 HPO clinical features (Orphanet curated; top 12 by frequency):

HPO ID	Term	Frequency
HP:0002170	Intracranial hemorrhage	Very frequent (80-99%)
HP:0002239	Gastrointestinal hemorrhage	Very frequent (80-99%)
HP:0000132	Menorrhagia	Frequent (30-79%)
HP:0000225	Gingival bleeding	Frequent (30-79%)
HP:0000421	Epistaxis	Frequent (30-79%)
HP:0000978	Bruising susceptibility	Frequent (30-79%)
HP:0004846	Prolonged bleeding after surgery	Frequent (30-79%)
HP:0005261	Joint hemorrhage	Frequent (30-79%)
HP:0008151	Prolonged prothrombin time	Frequent (30-79%)
HP:0000138	Ovarian cyst	Occasional (5-29%)
HP:0010881	Abnormality of the umbilical cord	Occasional (5-29%)
HP:0011891	Post-partum hemorrhage	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital factor VII deficiency
Mondo ID	MONDO:0009211
OMIM	227500
Orphanet	327
DOID	DOID:2215
NCIT	C131631
UMLS	C0272320
MedGen	473015
GARD	0002238
MedDRA	10016079
Is cancer (heuristic)	no

Also known as: congenital factor VII deficiency · congenital proconvertin deficiency · factor 7 deficiency · hypoproconvertinemia

Data availability: 101 ClinVar variants · 5 GenCC gene-disease records · 2 cell lines.

Disease family

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

Related subtypes (1): 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

101 retrieved; paginated sample, class counts are floors:

29 uncertain significance, 22 likely pathogenic, 19 pathogenic/likely pathogenic, 17 conflicting classifications of pathogenicity, 10 pathogenic, 2 not provided, 1 pathogenic/likely pathogenic; other, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1163548	NM_019616.4(F7):c.854G>A (p.Arg285His)	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
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
12085	NM_019616.4(F7):c.1099T>G (p.Cys367Gly)	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322860	NM_019616.4(F7):c.568C>T (p.Arg190Ter)	F7	Pathogenic	criteria provided, multiple submitters, no conflicts
1322861	NM_019616.4(F7):c.1263C>G (p.Tyr421Ter)	F7	Pathogenic	criteria provided, single submitter
1677255	NM_019616.4(F7):c.868G>A (p.Val290Met)	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1678759	NM_019616.4(F7):c.505+78G>A	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1684389	NM_019616.4(F7):c.517T>C (p.Cys173Arg)	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1691295	NM_019616.4(F7):c.225+1G>C	F7	Pathogenic	criteria provided, multiple submitters, no conflicts
2572145	NM_019616.4(F7):c.154dup (p.Glu52fs)	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265135	NM_019616.4(F7):c.1043G>T (p.Cys348Phe)	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2683442	NM_019616.4(F7):c.739+1G>A	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3029413	NM_019616.4(F7):c.178T>C (p.Cys60Arg)	F7	Pathogenic	criteria provided, single submitter
3352537	NM_019616.4(F7):c.1008G>A (p.Met336Ile)	F7	Pathogenic	criteria provided, single submitter
3382510	NM_019616.4(F7):c.64G>A (p.Val22Ile)	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3575772	NM_019616.4(F7):c.1157A>G (p.His386Arg)	F7	Pathogenic	criteria provided, single submitter
3629690	NM_019616.4(F7):c.1318C>T (p.Arg440Ter)	F7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3765536	NM_019616.4(F7):c.225+1G>A	F7	Pathogenic	criteria provided, single submitter
3768242	NM_019616.4(F7):c.1249A>G (p.Arg417Gly)	F7	Pathogenic	criteria provided, single submitter
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
4849355	NM_019616.4(F7):c.506-2A>G	F7	Pathogenic	criteria provided, single submitter
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

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
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

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
F7	HGNC:3544	ENSG00000057593	P08709	Coagulation factor VII	gencc,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.

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
Protease	1	36.6×	0.027

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

Expression context

Cohort genes with no expression data: 0.

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
buccal mucosa cell	1
liver	1
right lobe of liver	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
F7	1,224

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
F7	P08709	114

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus	1	1268.9×	0.002	F7
Gamma-carboxylation of protein precursors	1	1142.0×	0.002	F7
Removal of aminoterminal propeptides from gamma-carboxylated proteins	1	1142.0×	0.002	F7
Initiation of coagulation cascade	1	475.8×	0.003	F7
BMAL1:CLOCK,NPAS2 activates circadian expression	1	423.0×	0.003	F7
Regulation of clotting cascade	1	233.1×	0.004	F7

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
response to carbon dioxide	1	16852.0×	3e-04	F7
response to Thyroid stimulating hormone	1	16852.0×	3e-04	F7
response to astaxanthin	1	16852.0×	3e-04	F7
response to thyrotropin-releasing hormone	1	16852.0×	3e-04	F7
response to vitamin K	1	5617.3×	6e-04	F7
response to genistein	1	5617.3×	6e-04	F7
response to thyroxine	1	5617.3×	6e-04	F7
positive regulation of platelet-derived growth factor receptor signaling pathway	1	3370.4×	8e-04	F7
response to 2,3,7,8-tetrachlorodibenzodioxine	1	3370.4×	8e-04	F7
response to cholesterol	1	1685.2×	0.001	F7
positive regulation of positive chemotaxis	1	1404.3×	0.001	F7
positive regulation of leukocyte chemotaxis	1	1296.3×	0.001	F7
positive regulation of blood coagulation	1	1123.5×	0.001	F7
response to growth hormone	1	1123.5×	0.001	F7
animal organ regeneration	1	601.9×	0.003	F7
positive regulation of TOR signaling	1	495.6×	0.003	F7
response to estrogen	1	343.9×	0.004	F7
circadian rhythm	1	244.2×	0.005	F7
response to estradiol	1	198.3×	0.006	F7
blood coagulation	1	173.7×	0.006	F7
protein processing	1	170.2×	0.006	F7
response to hypoxia	1	95.8×	0.011	F7
positive regulation of cell migration	1	61.7×	0.016	F7

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
F7	NIACINAMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
F7	8	4

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: 1; 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	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: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07347249	PHASE2	RECRUITING	A Clinical Study to Assess Sutacimig in Participants With Congenital Factor VII Deficiency

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SUTACIMIG	2	1