congenital factor V deficiency

Summary

congenital factor V deficiency (MONDO:0009210) is a disease caused by F5 (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: F5 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 880
• Phenotypes (HPO): 19

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.1	Europe	Validated

Signs & symptoms

Clinical features (HPO)

19 HPO clinical features (Orphanet curated; top 19 by frequency):

HPO ID	Term	Frequency
HP:0000421	Epistaxis	Frequent (30-79%)
HP:0005261	Joint hemorrhage	Frequent (30-79%)
HP:0000132	Menorrhagia	Occasional (5-29%)
HP:0000225	Gingival bleeding	Occasional (5-29%)
HP:0000790	Hematuria	Occasional (5-29%)
HP:0000978	Bruising susceptibility	Occasional (5-29%)
HP:0001934	Persistent bleeding after trauma	Occasional (5-29%)
HP:0002239	Gastrointestinal hemorrhage	Occasional (5-29%)
HP:0004846	Prolonged bleeding after surgery	Occasional (5-29%)
HP:0006298	Prolonged bleeding after dental extraction	Occasional (5-29%)
HP:0007420	Spontaneous hematomas	Occasional (5-29%)
HP:0011890	Prolonged bleeding following procedure	Occasional (5-29%)
HP:0011891	Post-partum hemorrhage	Occasional (5-29%)
HP:0030137	Prolonged bleeding following circumcision	Occasional (5-29%)
HP:0030140	Oral cavity bleeding	Occasional (5-29%)
HP:0002105	Hemoptysis	Very rare (<1-4%)
HP:0002170	Intracranial hemorrhage	Very rare (<1-4%)
HP:0002573	Hematochezia	Very rare (<1-4%)
HP:0100608	Metrorrhagia	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital factor V deficiency
Mondo ID	MONDO:0009210
OMIM	227400
Orphanet	326
DOID	DOID:2216
NCIT	C98938
SNOMED CT	88776002
UMLS	C0015499
MedGen	4633
GARD	0002237
MedDRA	10048930
Is cancer (heuristic)	no

Also known as: congenital factor V deficiency · hereditary Factor V deficiency · hereditary factor V deficiency · labile factor deficiency · Owren disease · Parahemophilia · Proaccelerin deficiency

Data availability: 880 ClinVar variants · 3 GenCC gene-disease records · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › hemorrhagic disease › congenital factor V deficiency

Related subtypes (27): inherited bleeding disorder, platelet-type, factor VII deficiency, factor X deficiency, purpura, vascular hemostatic disease, congenital high-molecular-weight kininogen deficiency, congenital factor XII deficiency, alpha-2-plasmin inhibitor deficiency, hemophilia A, hemophilia B, East Texas bleeding disorder, congenital factor XI deficiency, 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 factor XIII deficiency, congenital fibrinogen deficiency, combined deficiency of factor V and factor VIII, acquired hemophilia, fetal and neonatal alloimmune thrombocytopenia, hereditary von Willebrand disease, acquired von willebrand syndrome, prothrombin deficiency, hemophilia B leyden

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

600 retrieved; paginated sample, class counts are floors:

376 likely benign, 55 uncertain significance, 50 conflicting classifications of pathogenicity, 45 benign/likely benign, 29 pathogenic, 19 benign, 18 likely pathogenic, 8 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1452773	NM_000130.5(F5):c.1600C>T (p.Arg534Ter)	F5	Pathogenic	criteria provided, single submitter
2701935	NM_000130.5(F5):c.3322del (p.Thr1108fs)	F5	Pathogenic	criteria provided, single submitter
2702927	NM_000130.5(F5):c.987C>A (p.Cys329Ter)	F5	Pathogenic	criteria provided, single submitter
2711546	NM_000130.5(F5):c.3532G>T (p.Glu1178Ter)	F5	Pathogenic	criteria provided, single submitter
2712195	NM_000130.5(F5):c.4900C>T (p.Arg1634Ter)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2728317	NM_000130.5(F5):c.5261del (p.Gly1754fs)	F5	Pathogenic	criteria provided, single submitter
2734020	NM_000130.5(F5):c.3799del (p.Leu1267fs)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2734021	NM_000130.5(F5):c.3088C>T (p.Arg1030Ter)	F5	Pathogenic	criteria provided, multiple submitters, no conflicts
2734022	NM_000130.5(F5):c.2743_2744del (p.Thr915fs)	F5	Pathogenic	criteria provided, single submitter
2734024	NM_000130.5(F5):c.1258G>T (p.Gly420Cys)	F5	Pathogenic	criteria provided, multiple submitters, no conflicts
2734025	NM_000130.5(F5):c.653T>C (p.Phe218Ser)	F5	Pathogenic	criteria provided, single submitter
2734026	NM_000130.5(F5):c.286G>C (p.Asp96His)	F5	Pathogenic	criteria provided, multiple submitters, no conflicts
2745996	NM_000130.5(F5):c.4465C>T (p.Gln1489Ter)	F5	Pathogenic	criteria provided, single submitter
2746047	NM_000130.5(F5):c.4317_4318del (p.Pro1440fs)	F5	Pathogenic	criteria provided, single submitter
2761343	NM_000130.5(F5):c.2228C>A (p.Ser743Ter)	F5	Pathogenic	criteria provided, single submitter
2766288	NM_000130.5(F5):c.4705_4706delinsTA (p.Ala1569Ter)	F5	Pathogenic	criteria provided, single submitter
2845595	NM_000130.5(F5):c.4083dup (p.Ser1362fs)	F5	Pathogenic	criteria provided, single submitter
2860268	NM_000130.5(F5):c.2521del (p.Gln841fs)	F5	Pathogenic	criteria provided, single submitter
2866617	NM_000130.5(F5):c.5453del (p.Leu1818fs)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2884086	NM_000130.5(F5):c.5143C>T (p.Arg1715Ter)	F5	Pathogenic	criteria provided, single submitter
2884844	NM_000130.5(F5):c.3646G>T (p.Glu1216Ter)	F5	Pathogenic	criteria provided, single submitter
2885367	NM_000130.5(F5):c.155C>G (p.Ser52Ter)	F5	Pathogenic	criteria provided, single submitter
2893671	NM_000130.5(F5):c.436C>T (p.Arg146Ter)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2895285	NM_000130.5(F5):c.2021del (p.Lys674fs)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2896365	NM_000130.5(F5):c.4861C>T (p.Arg1621Ter)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2896674	NM_000130.5(F5):c.5793C>G (p.Tyr1931Ter)	F5	Pathogenic	criteria provided, single submitter
2904412	NM_000130.5(F5):c.597_598del (p.Glu200fs)	F5	Pathogenic	criteria provided, single submitter
293622	NM_000130.5(F5):c.2218C>T (p.Arg740Ter)	F5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2956469	NM_000130.5(F5):c.5645G>A (p.Trp1882Ter)	F5	Pathogenic	criteria provided, single submitter
2971118	NM_000130.5(F5):c.2946G>A (p.Trp982Ter)	F5	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 11 · 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
F5	Strong	Autosomal recessive	congenital factor V deficiency	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
F5	Orphanet:131	Budd-Chiari syndrome
F5	Orphanet:326	Congenital factor V deficiency
F5	Orphanet:329217	Cerebral sinovenous thrombosis
F5	Orphanet:391320	East Texas bleeding disorder
F5	Orphanet:599579	Factor V Amsterdam bleeding disorder
F5	Orphanet:600194	Factor V Atlanta bleeding disorder
FGA	Orphanet:101041	Familial hypofibrinogenemia
FGA	Orphanet:248408	Familial hypodysfibrinogenemia
FGA	Orphanet:93562	AFib amyloidosis
FGA	Orphanet:98880	Familial afibrinogenemia
FGA	Orphanet:98881	Familial dysfibrinogenemia

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
F5	HGNC:3542	ENSG00000198734	P12259	Coagulation factor V	gencc,clinvar
FGA	HGNC:3661	ENSG00000171560	P02671	Fibrinogen alpha chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
F5	Coagulation factor V	Central regulator of hemostasis.
FGA	Fibrinogen alpha chain	Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
F5	Other/Unknown	no		FA58C, Cupredoxin, Galactose-bd-like_sf
FGA	Other/Unknown	no		Fibrinogen_a/b/g_C_dom, Fibrinogen_a/b/g_coil_dom, Fibrinogen_a/b/g_C_1

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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
liver	2
right lobe of liver	2
choroid plexus epithelium	1
islet of Langerhans	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
F5	206	broad	marker	right lobe of liver, liver, choroid plexus epithelium
FGA	153	tissue_specific	marker	right lobe of liver, liver, islet of Langerhans

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGA	2,327
F5	1,754

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGA	P02671	39
F5	P12259	18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 29. 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
Post-translational protein phosphorylation	2	100.2×	0.001	F5, FGA
Platelet degranulation	2	87.8×	0.001	F5, FGA
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	2	86.5×	0.001	F5, FGA
Defective cleavage of FV variant at a.a.534	1	1903.3×	0.003	F5
Defective cleavage of FV variant at R334	1	1903.3×	0.003	F5
Aggregated β-amyloid interacts with fibrinogen	1	1427.5×	0.003	FGA
Fibrin formation	1	439.2×	0.008	FGA
p130Cas linkage to MAPK signaling for integrins	1	380.7×	0.008	FGA
GRB2:SOS provides linkage to MAPK signaling for Integrins	1	356.9×	0.008	FGA
Amplification and propagation of coagulation cascade	1	317.2×	0.008	F5
MyD88 deficiency (TLR2/4)	1	300.5×	0.008	FGA
IRAK4 deficiency (TLR2/4)	1	285.5×	0.008	FGA
Regulation of TLR by endogenous ligand	1	248.3×	0.009	FGA
Initiation of coagulation cascade	1	237.9×	0.009	F5
Integrin signaling	1	211.5×	0.009	FGA
Cargo concentration in the ER	1	167.9×	0.010	F5
Signaling by high-kinase activity BRAF mutants	1	158.6×	0.010	FGA
MAP2K and MAPK activation	1	142.8×	0.010	FGA
Signaling by RAF1 mutants	1	139.3×	0.010	FGA
Signaling by moderate kinase activity BRAF mutants	1	126.9×	0.010	FGA
Paradoxical activation of RAF signaling by kinase inactive BRAF	1	126.9×	0.010	FGA
Signaling downstream of RAS mutants	1	126.9×	0.010	FGA
Regulation of clotting cascade	1	116.5×	0.011	F5
Signaling by BRAF and RAF1 fusions	1	85.2×	0.014	FGA
COPII-mediated vesicle transport	1	81.6×	0.014	F5
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1	76.1×	0.015	FGA
Integrin cell surface interactions	1	67.2×	0.016	FGA
ER-Phagosome pathway	1	64.9×	0.016	FGA
Amyloid fiber formation	1	51.4×	0.019	FGA

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
blood coagulation, common pathway	1	4213.0×	0.004	FGA
response to vitamin K	1	2808.7×	0.004	F5
induction of bacterial agglutination	1	1404.3×	0.005	FGA
blood coagulation, fibrin clot formation	1	842.6×	0.005	FGA
positive regulation of peptide hormone secretion	1	766.0×	0.005	FGA
plasminogen activation	1	648.1×	0.005	FGA
positive regulation of heterotypic cell-cell adhesion	1	648.1×	0.005	FGA
protein polymerization	1	495.6×	0.006	FGA
fibrinolysis	1	421.3×	0.006	FGA
positive regulation of vasoconstriction	1	300.9×	0.007	FGA
positive regulation of exocytosis	1	300.9×	0.007	FGA
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	1	290.6×	0.007	FGA
blood circulation	1	255.3×	0.007	F5
negative regulation of endothelial cell apoptotic process	1	247.8×	0.007	FGA
positive regulation of substrate adhesion-dependent cell spreading	1	187.2×	0.008	FGA
positive regulation of protein secretion	1	172.0×	0.008	FGA
platelet aggregation	1	168.5×	0.008	FGA
response to calcium ion	1	159.0×	0.008	FGA
blood coagulation	1	86.9×	0.015	F5
cell-matrix adhesion	1	81.8×	0.015	FGA
protein-containing complex assembly	1	56.9×	0.020	FGA
positive regulation of ERK1 and ERK2 cascade	1	42.6×	0.025	FGA
adaptive immune response	1	42.1×	0.025	FGA
innate immune response	1	16.8×	0.059	FGA

Therapeutics

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
F5	EDOXABAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
F5	2	4
FGA	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
EDOXABAN	4	F5
RAZAXABAN	2	F5

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
F5	10	Binding:10

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

2 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)
EDOXABAN	4	F5
RAZAXABAN	2	F5

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	F5
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	FGA

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)
FGA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.