Hemophilia

Summary

Hemophilia (MONDO:0018660) is a disease with 1 cohort gene and 154 clinical trials. Top therapeutic interventions include octocog alfa, eptacog alfa (activated), and marstacimab.

At a glance

• Prevalence: 1-9 / 100 000 (China) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 154

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	6.46	China	Validated
Annual incidence	1-9 / 100 000	6.25	Europe	Not yet validated
Point prevalence	1-9 / 100 000	7.7	Europe	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	hemophilia
Mondo ID	MONDO:0018660
Orphanet	448
DOID	DOID:0061030
NCIT	C3093
SNOMED CT	90935002
UMLS	C0684275
MedGen	146334
GARD	0010418
MedDRA	10061992
Is cancer (heuristic)	no

Also known as: hemophilia

Data availability: 1 ClinVar variant · 1 cell line.

Disease family

An umbrella term covering 4 Mondo subtypes.

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

Related subtypes (27): factor XIII deficiency, factor VII 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, 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 (4): hemophilia A, hemophilia B, acquired hemophilia, factor XI 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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2775419	NM_000131.4(F7):c.-96C>A	F7	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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	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: 154.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	119
PHASE3	10
PHASE1	10
PHASE4	5
PHASE2	5
PHASE1/PHASE2	3
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06752850	PHASE4	ACTIVE_NOT_RECRUITING	A Study to Investigate the Course of Synovial Hypertrophy in Patients With Haemophilia A on Efanesoctocog Alfa Prophylaxis
NCT07406139	PHASE4	RECRUITING	PCC Treatment for Hemophilia Patients With Inhibitor（2022PCC-A）
NCT00707772	PHASE4	COMPLETED	Pegasys® Plus Ribavirin in Hemophilic Patients With Hepatitis C Virus Infection
NCT04108260	PHASE4	UNKNOWN	The Effectiveness of Recombinant Coagulation Factor IX With Recombinant Albumin (rIX-FP) in Severe Hemophilia B Patients
NCT05728528	PHASE4	COMPLETED	Impact of Moderate Intensity Physical Activities on PK-guided EHL FVIII Concentrates Prophylaxis Severe HA Patients
NCT03754790	PHASE3	ACTIVE_NOT_RECRUITING	Long-term Safety and Efficacy Study of Fitusiran in Patients With Hemophilia A or B, With or Without Inhibitory Antibodies to Factor VIII or IX
NCT03974113	PHASE3	ACTIVE_NOT_RECRUITING	Fitusiran Prophylaxis in Male Pediatric Subjects Aged 1 to Less Than 12 Years With Hemophilia A or B
NCT05662319	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Test a Medicine (Fitusiran) Injected Under the Skin for Preventing Bleeding Episodes in Male Adolescent or Adult Participants With Severe Hemophilia
NCT06922045	PHASE3	RECRUITING	Phase III Clinical Trial of STSP-0601 for Injection in Hemophilia Patients
NCT07285460	PHASE3	RECRUITING	A Study to Investigate the Efficacy and Safety of Fitusiran Prophylaxis in Male Participants Aged 1 to Less Than 12 Years With Hemophilia A or B
NCT00606060	PHASE3	COMPLETED	BAY14-2222 Continuous Infusion in Surgeries
NCT02306694	PHASE3	COMPLETED	Prospective Biomarkers of Bone Metabolism in Hemophilia A
NCT02548143	PHASE3	COMPLETED	LR769 in Congenital Hemophilia Patients With Inhibitors Undergoing Elective Surgery or Invasive Procedures
NCT03549871	PHASE3	COMPLETED	A Study of Fitusiran in Severe Hemophilia A and B Patients Previously Receiving Factor or Bypassing Agent Prophylaxis
NCT05695391	PHASE3	TERMINATED	A Phase 3 Study of the Safety and Efficacy of Coagulation Factor VIIa (Recombinant) for the Prevention of Excessive Bleeding in Patients With Congenital Hemophilia A or B With Inhibitors to Factor VIII or IX Undergoing Elective Major Surgical Procedures SCOPE HIM
NCT00055341	PHASE2	COMPLETED	Treatment of Hepatitis C in Hemophilic Patients With HIV
NCT02586012	PHASE2	TERMINATED	Weight-based Dosing in Hemophilia A
NCT05027230	PHASE1/PHASE2	COMPLETED	A Safety and Efficacy Study of STSP-0601 in Adult Patients With Hemophilia A or B With Inhibitor
NCT05421429	PHASE2	COMPLETED	KN057 Multiple Dose Study in Moderately Severe to Severe Hemophilia
NCT05619926	PHASE2	COMPLETED	Safety and Efficacy of STSP-0601 in Adult Patients With Hemophilia A or B Without Inhibitor
NCT05920512	PHASE1/PHASE2	UNKNOWN	Combination Regimen With Sodium Valproate for Severe Hemophilia: a Single-arm, Phase 1, Pilot Trial.
NCT06010953	PHASE1/PHASE2	COMPLETED	SS109 and NovoSeven ® PK / PD Profile, and Preliminary Efficacy and Safety of SS109 on Demand Treatment
NCT06289166	PHASE2	COMPLETED	Safety and Efficacy of STSP-0601 in Adult Patients with Hemophilia a or B with Inhibitor
NCT01191372	PHASE1	TERMINATED	First-in-Human and Proof-of-Mechanism Study of ARC19499 Administered to Hemophilia Patients
NCT01704521	PHASE1	COMPLETED	Viral Kinetics in HCV Clearance in Subjects With Hemophilia
NCT01708564	PHASE1	COMPLETED	A Phase I Safety, Pharmacokinetics and Pharmacodynamics Study of Recombinant Factor VIIa in Adult Patients With Hemophilia A or B
NCT02060305	PHASE1	TERMINATED	Intra-articular Bevacizumab for Recurrent Hemarthroses at Target Joints With Chronic Hemophilic Synovitis
NCT02108132	PHASE1	UNKNOWN	Allogenic Bone Marrow Derived Mesenchymal Stem Cell Therapy in Cases of Hemophilia
NCT03855696	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, PK and PD of MG1113 in Healthy Subjects and Hemophilia Patients
NCT03996486	PHASE1	WITHDRAWN	Study to Test the Safety of an Investigational Drug Given Repeatedly to Adult Men With Severe Hemophilia
NCT04747964	PHASE1	COMPLETED	A Safety Study of STSP-0601 in Adult Patients With Hemophilia A or B With Inhibitor
NCT04878731	PHASE1	COMPLETED	Study to Evaluate Safety and Tolerability of a Single Dose of PF-06741086 in Chinese Adult Participants With Severe Hemophilia
NCT05493631	PHASE1	COMPLETED	A Phase 1b Study to Assess the Safety, Tolerability, PK and PD of MG1113 in Hemophilia Patient
NCT06345833	EARLY_PHASE1	RECRUITING	Topical and Local TXA in Facelifts - A Randomized Controlled Double Blinded Study
NCT03272568	EARLY_PHASE1	COMPLETED	Extended Half Life Factor (EHF) Products For Heavy Menstrual Bleeding in Hemophilia Carriers
NCT02453542	Not specified	RECRUITING	Global Haemostatic Methods Following Administration of Bypassing Agents to Patients With Haemophilia With Inhibitors
NCT03549858	Not specified	RECRUITING	Patient Reported Outcomes Burdens and Experiences - Phase 3
NCT04278404	Not specified	RECRUITING	Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS)
NCT04384341	Not specified	RECRUITING	Haemophilia and Bone Loss - PHILEOS Study
NCT04398628	Not specified	RECRUITING	ATHN Transcends: A Natural History Study of Non-Neoplastic Hematologic Disorders

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
OCTOCOG ALFA	4	3
EPTACOG ALFA (ACTIVATED)	4	2
MARSTACIMAB	4	2
ALBUTREPENONACOG ALFA	4	1
ANTIHEMOPHILIC FACTOR, PEGYLATED (MW 20000) HUMAN SEQUENCE RECOMBINANT	4	1
EFANESOCTOCOG ALFA	4	1
PEGINTERFERON ALFA-2A	4	1
TELAPREVIR	4	1
FITUSIRAN	3	5
BLOOD, WHOLE	3	1
BAY-1093884	2	1
ISOXAFLUTOLE	2	1
ARC-19499	1	1
CHEMBL443336	0	1
CHEMBL5181771	0	1