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Protein / target

Coagulation factor IX

Encoded byF9P00740Homo sapiensSwiss-Prot
UniProt: P00740Ensembl: ENSG00000101981HGNC: HGNC:3551NCBI Gene: 2158
Clinically validated
Therapeutic maturity
9
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Structure with Ligand

Protein at a glance

Biological role

Serine-type endopeptidase

Strongest disease association

Hemophilia B

Via encoding gene F9 · Genetic evidence · score 0.99

Therapeutic position

Established drug target

Research activity

Emerging research

2 papers · latest 2018

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa

View complete UniProt function annotation

Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa (PubMed:8295821, PubMed:2592373, PubMed:20121197, PubMed:20121198, PubMed:1730085, PubMed:19846852, PubMed:39880037)

Subcellular location

Secreted
Domains and Gene Ontology detail (18)

Domains & features

GlaEGF-like 1; calcium-bindingEGF-like 2Peptidase S1

Gene Ontology

  • Cendoplasmic reticulum lumen
  • Cextracellular exosome
  • Cextracellular matrix
  • Cextracellular region
  • Cextracellular space
  • CGolgi lumen
  • Cplasma membrane
  • Fcalcium ion binding
  • Fendopeptidase activity
  • Fmetal ion binding
  • Fserine-type endopeptidase activity
  • Pblood coagulation

461 aa · 52 kDa · 2 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Lipid & lipoprotein metabolismUniProtHaemostasisUniProt · GOProteolysisGO
View supporting evidence

Lipid & lipoprotein metabolism

  • ·Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pat…

Haemostasis

  • ·Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pat…
  • ·blood coagulation

Proteolysis

  • ·endopeptidase activity
  • ·serine-type endopeptidase activity
  • ·proteolysis

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Approved medicines with mapped indications

5 medicines · 3 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Hemorrhage4 medicines
emicizumabetranacogene dezaparvovecfidanacogene elaparvovecvaloctocogene roxaparvovec
Hemophilia B3 medicines
albutrepenonacog alfaetranacogene dezaparvovecfidanacogene elaparvovec
Hemophilia A2 medicines
emicizumabvaloctocogene roxaparvovec

9 medicines meet Open Targets' target-level approved-medicine definition; the 5 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

5

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

etranacogene dezaparvovec
Narrow target profileApprovedExogenous protein

Coagulation factor IX exogenous protein

Indicated for Hemophilia B, Hemorrhage

Direct interaction with this protein · Only this protein recorded as a target

albutrepenonacog alfa
Narrow target profileApprovedExogenous protein

Coagulation factor IX exogenous protein

Indicated for Hemophilia B

Direct interaction with this protein · Only this protein recorded as a target

fidanacogene elaparvovec
Narrow target profileApprovedExogenous gene

Coagulation factor IX exogenous gene

Indicated for Hemophilia B, Hemorrhage

Direct interaction with this protein · Only this protein recorded as a target

valoctocogene roxaparvovec
Narrow target profileApprovedExogenous protein

Coagulation factor IX exogenous protein

Indicated for Hemophilia A, Hemorrhage

Direct interaction with this protein · Only this protein recorded as a target

emicizumab
ApprovedOther

Coagulation factor IX and X other

Indicated for Hemophilia A, Hemorrhage

Acts on a complex — shared with F10 · 1 of 2 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene F9

Gene-level evidence surfaced through the gene F9that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Hemophilia B
1.00Well supported

Genetic evidence dominant · Open Targets 0.89

Hemophilia A
0.98Well supported

Genetic evidence dominant · Open Targets 0.76

Venous Thromboembolism
0.86Well supported

Genetic evidence dominant · Open Targets 0.52

View evidence synthesis (3)
Hemophilia BWell supported
1.00
agreement 0.90–1.00
Genetic46%Clinical35%Pathway16%Literature3%Genetic literaturedup

Open Targets aggregate 0.89 · 4 independent evidence families · 1 not counted as duplicate

Hemophilia AWell supported
0.98
agreement 0.88–1.00
Genetic47%Clinical38%Pathway13%Literature2%

Open Targets aggregate 0.76 · 4 independent evidence families

Venous ThromboembolismWell supported
0.86
agreement 0.72–1.00
Genetic99%Literature1%

Open Targets aggregate 0.52 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Hemophilia B0.89
Hemophilia A0.76
Venous Thromboembolism0.52

Drug development

12 compounds recorded · 9 approved · 3 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 5 drugs that target this protein in Forefront's canonical graph (5 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
TRENONACOG ALFAPhase 3
VALOCTOCOGENE ROXAPARVOVECApproval
FIDANACOGENE ELAPARVOVECApproval
COAGULATION FACTOR IX RECOMBINANT HUMANApproval
ALBUTREPENONACOG ALFAApproval
EMICIZUMABApproval
PEGNIVACOGINPhase 3
ETRANACOGENE DEZAPARVOVECApproval
EFTRENONACOG ALFAApproval
NONACOG BETA PEGOLApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (half-life data and small molecule binder) — no clinical-stage drug of this modality recorded.

Other modalities — Strong

Approved Drug support this modality.

View underlying tractability evidence (9)
SM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Half-life DataPR · Small Molecule BinderOC · Approved Drug

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

Understanding Treatment Outcomes and Immunologic Mechanisms in ALtuviiio Immune Tolerance InductionPHASE4

NOT_YET_RECRUITING · via emicizumab · NCT07158606

GENEr8-JPN: A Phase 3 Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Japanese Hemophilia A Patients With Residual FVIII Levels ≤ 1 IU/dL Receiving Prophylactic FVIII InfusionsPHASE3

ACTIVE_NOT_RECRUITING · via valoctocogene roxaparvovec · NCT06224907

Phase III, Open-label, Single-dose, Multi-center, Multinational Trial Investigating a Serotype 5 Adeno-associated Viral Vector Containing the Padua Variant of a Codon-optimized Human Factor IX Gene (AAV5-hFIXco-Padua, AMT-061) Administered to Adult Subjects With Severe or Moderately Severe Hemophilia BPHASE3

COMPLETED · via etranacogene dezaparvovec · NCT03569891

An Open-label, Single-arm Treatment Study to Investigate the Safety and Tolerability of Switching From Emicizumab to Fitusiran Prophylaxis in Male Participants Aged ≥12 Years of Age With Severe Hemophilia A, With or Without InhibitorsPHASE4

RECRUITING · via emicizumab · NCT06145373

View all trials (26)
Prospective, Single-Arm, Open-Label Use of Hemlibra (Emicizumab) in the Treatment of Mild Hemophilia APHASE4

RECRUITING · via emicizumab · NCT04567511

A Multicenter, Open-Label Phase IV Study to Evaluate Overall Health, Physical Activity, and Joint Outcomes, in Participants Aged ≥13 and <70 Years With Severe or Moderate Hemophilia A Without FVIII Inhibitors on Emicizumab ProphylaxisPHASE4

ACTIVE_NOT_RECRUITING · via emicizumab · NCT05181618

aPCC and Emicizumab Safety Study in Congenital Hemophilia A Patients With Inhibitors (SAFE Study: Safety of aPCC Following Emicizumab Prophylaxis)PHASE3

RECRUITING · via emicizumab · NCT04563520

A Multicenter, Randomized, Open-Label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of NXT007 Prophylaxis Versus Emicizumab Prophylaxis in People With Hemophilia APHASE3

RECRUITING · via emicizumab · NCT07416604

A Phase III, Multicenter, Open-Label Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Emicizumab Prophylaxis in Patients With Type 3 Von Willebrand DiseasePHASE3

RECRUITING · via emicizumab · NCT06998524

Comparison of Low Dose Emicizumab and Low Dose Factor VIII as a Prophylaxis in Hemophilia A Patients- a Randomized Control Trial'PHASE2/PHASE3

NOT_YET_RECRUITING · via emicizumab · NCT06938659

A Phase IIIb, Multicenter, Open-Label, Single-Arm Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Emicizumab in Patients From Birth to 12 Months of Age With Hemophilia A Without InhibitorsPHASE3

ACTIVE_NOT_RECRUITING · via emicizumab · NCT04431726

Emicizumab in Patients With Acquired Hemophilia A: Multicenter, Single-arm, Open-label Clinical TrialPHASE2

ACTIVE_NOT_RECRUITING · via emicizumab · NCT05345197

Emicizumab for Severe VON Willebrand Disease (VWD) and VWD/Hemophilia APHASE1

RECRUITING · via emicizumab · NCT05500807

POCUS: Hemostatic Potential and Joint Health in Patients With Severe Hemophilia A on Novel Replacement TherapiesPHASE4

WITHDRAWN · via emicizumab · NCT04690322

A Multi-center, Prospective Study Evaluating the Rate of Inhibitor Recurrence Following Successful ITI in Patients Receiving Ongoing Once Per Weekly Factor VIII Therapy Along With Emicizumab and in Patients Who Discontinue FVIII Therapy and Are on Emicizumab for ProphylaxisPHASE4

UNKNOWN · via emicizumab · NCT04621916

Prospective, Single-arm, Open-label Use of Hemlibra (Emicizumab) to Treat Hemophilic PseudotumorPHASE4

TERMINATED · via emicizumab · NCT03921294

A Phase IV, Multicenter, Single-Arm, Open-Label Study of Emicizumab Prophylaxis in Patients With Hemophilia A With or Without Inhibitors Undergoing Minor Surgical ProceduresPHASE4

TERMINATED · via emicizumab · NCT03361137

Phase III Multi-Center, Randomized, Controlled Inhibitor Eradication Trial, Comparing Eloctate Immune Tolerance Induction (ITI) Plus Emicizumab vs. Eloctate ITI Alone to Eradicate Inhibitor Formation in Severe Hemophilia APHASE3

TERMINATED · via emicizumab · NCT04303572

Multicenter, Randomized Phase III Inhibitor Prevention Trial, Comparing Eloctate vs. Emicizumab to Prevent Inhibitor Formation in Severe Hemophilia APHASE3

TERMINATED · via emicizumab · NCT04303559

A Phase 3b, Single Arm, Open-Label Study to Evaluate the Efficacy and Safety of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII, With Prophylactic Corticosteroids in Hemophilia A PatientsPHASE3

COMPLETED · via valoctocogene roxaparvovec · NCT04323098

A Multicenter, Open-Label Study to Evaluate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Emicizumab in Patients With Mild or Moderate Hemophilia A Without FVIII InhibitorsPHASE3

COMPLETED · via emicizumab · NCT04158648

A Randomized, Multicenter, Open-Label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus No Prophylaxis in Hemophilia A PatientsPHASE3

COMPLETED · via emicizumab · NCT03315455

A Phase 3 Open-Label, Single-Arm Study To Evaluate The Efficacy and Safety of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII at a Dose of 4E13vg/kg in Hemophilia A Patients With Residual FVIII Levels ≤1IU/dL Receiving Prophylactic FVIII InfusionsPHASE3

COMPLETED · via valoctocogene roxaparvovec · NCT03392974

A Phase 3 Open-Label, Single-Arm Study To Evaluate The Efficacy and Safety of BMN 270, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A Patients With Residual FVIII Levels ≤ 1 IU/dL Receiving Prophylactic FVIII InfusionsPHASE3

COMPLETED · via valoctocogene roxaparvovec · NCT03370913

A Single-Arm, Multicenter Phase IIIB Clinical Trial to Evaluate the Safety and Tolerability of Prophylactic Emicizumab in Hemophilia A Patients With InhibitorsPHASE3

COMPLETED · via emicizumab · NCT03191799

A Multicenter, Open-Label, Phase III Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Emicizumab Given Every 4 Weeks (Q4W) in Patients With Hemophilia APHASE3

COMPLETED · via emicizumab · NCT03020160

A Randomized, Multicenter, Open-Label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Patients Without InhibitorsPHASE3

COMPLETED · via emicizumab · NCT02847637

A Multicenter, Open-Label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneous Administration of Emicizumab in Hemophilia A Pediatric Patients With InhibitorsPHASE3

COMPLETED · via emicizumab · NCT02795767

A Randomized, Multicenter, Open-Label, Phase III Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Patients With InhibitorsPHASE3

COMPLETED · via emicizumab · NCT02622321

Emicizumab in Patients With Acquired Hemophilia A: Multicenter, Single-arm, Open-label Clinical TrialPHASE2

COMPLETED · via emicizumab · NCT04188639

ClinicalTrials.gov via the drug-target graph.

What's happening now

7

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 5 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Withdrawn from market2025-05-15

    Market withdrawal: Beqvez (previously Durveqtix) (EMA)

    ema · market · ema · via fidanacogene elaparvovec

  2. Regulatory approval2023-02-20

    Approval: Hemgenix (EMA)

    ema · regulatory · ema · via etranacogene dezaparvovec

  3. Regulatory approval2022-08-24

    Approval: Roctavian (EMA)

    ema · regulatory · ema · via valoctocogene roxaparvovec

  4. New publication2019-12-01
    A multicenter, open-label phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors.

    Blood · 2019 · 289 citations · Europe PMC · via emicizumab

  5. New publication2018-08-01
    Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors.

    The New England journal of medicine · 2018 · 574 citations · Europe PMC · via emicizumab

  6. Accelerated approval granted2018-02-23

    Accelerated approval: Hemlibra (EMA)

    ema · regulatory · ema · via emicizumab

  7. Regulatory approval2016-05-11

    Approval: Idelvion (EMA)

    ema · regulatory · ema · via albutrepenonacog alfa

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.

Research activity

2 papers · to 2018

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Long-term safety and efficacy of factor IX gene therapy in hemophilia B.1,004 cites

Nathwani AC · The New England journal of medicine · 2014

Targeted genome engineering in human induced pluripotent stem cells from patients with hemophilia B using the CRISPR-Cas9 system.54 cites

Lyu C · Stem cell research & therapy · 2018

Recent

Targeted genome engineering in human induced pluripotent stem cells from patients with hemophilia B using the CRISPR-Cas9 system.

Lyu C · Stem cell research & therapy · 2018

Long-term safety and efficacy of factor IX gene therapy in hemophilia B.

Nathwani AC · The New England journal of medicine · 2014

Europe PMC papers linked directly to this protein.

Related family literature

1

Papers about “Serine Proteases” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.

Lipoprotein(a) as a Risk Factor for Cardiovascular Diseases: Pathophysiology and Treatment Perspectives.

Vinci P · International journal of environmental research and public health · 2023

via Serine Proteases

Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.