F9

Summary

F9 (coagulation factor IX, HGNC:3551) is a protein-coding gene on chromosome Xq27.1, encoding Coagulation factor IX (P00740). 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. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes vitamin K-dependent coagulation factor IX that circulates in the blood as an inactive zymogen. This factor is converted to an active form by factor XIa, which excises the activation peptide and thus generates a heavy chain and a light chain held together by one or more disulfide bonds. The role of this activated factor IX in the blood coagulation cascade is to activate factor X to its active form through interactions with Ca+2 ions, membrane phospholipids, and factor VIII. Alterations of this gene, including point mutations, insertions and deletions, cause factor IX deficiency, which is a recessive X-linked disorder, also called hemophilia B or Christmas disease. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing.

Source: NCBI Gene 2158 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hemophilia B (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 713 total — 206 pathogenic, 111 likely-pathogenic (top 5% of genes corpus-wide)
• GTEx eGene: eQTL in 0 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 18
• Drug target: yes — 11 curated mechanism-of-action drugs, 1 via a complex or family; 2 molecules with ChEMBL bioactivity
• Approved drugs (ChEMBL mechanism of action): 8 — Albutrepenonacog Alfa, Coagulation Factor Ix Human, Coagulation Factor Ix Recombinant Human, +5 more
• Approved drugs acting on a complex or family including it: 1 — Emicizumab (Coagulation factor IX and X)
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000133

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3551
Approved symbol	F9
Name	coagulation factor IX
Location	Xq27.1
Locus type	gene with protein product
Status	Approved
Aliases	FIX
Ensembl gene	ENSG00000101981
Ensembl biotype	protein_coding
OMIM	300746
Entrez	2158

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000218099

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 5: 1

ENST00000218099, ENST00000394090, ENST00000479617, ENST00000643157, ENST00001109334, ENST00001109335, ENST00001117660, ENST00001126573, ENST00001132443

RefSeq mRNA: 2 — MANE Select: NM_000133 NM_000133, NM_001313913

CCDS: CCDS14666, CCDS83495

Canonical transcript exons

ENST00000218099 — 8 exons

Exon	Start	End
ENSE00000677287	139537010	139537173
ENSE00001029145	139561524	139563459
ENSE00001173311	139560741	139560855
ENSE00001173315	139551062	139551264
ENSE00001173320	139548363	139548491
ENSE00001173327	139541076	139541189
ENSE00001173335	139537362	139537386
ENSE00003674048	139530739	139530852

Expression profiles

Bgee: expression breadth broad, 45 present calls, max score 98.70.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.6727 / max 1225.1303, expressed in 10 samples.

Highest expression (Bgee): lobe of liver, liver, secondary oocyte, oocyte, primordial germ cell in gonad.

Genetic regulation across tissues (GTEx eQTL / sQTL)

F9 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 0 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

1 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Liver	sqtl	7.4e-03	-0.40	X:139558433:G:C

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
197749	2.6727	10

Top tissues by expression

showing 100 of 257 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.70	gold quality
liver	UBERON:0002107	98.49	gold quality
secondary oocyte	CL:0000655	67.54	gold quality
oocyte	CL:0000023	65.46	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	59.31	gold quality
endometrium epithelium	UBERON:0004811	54.60	gold quality
cranial nerve II	UBERON:0000941	51.11	silver quality
frontal pole	UBERON:0002795	50.41	gold quality
quadriceps femoris	UBERON:0001377	50.38	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
tibialis anterior	UBERON:0001385	50.21	silver quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
pancreatic ductal cell	CL:0002079	49.94	silver quality
thymus	UBERON:0002370	49.51	gold quality
vastus lateralis	UBERON:0001379	49.45	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
deltoid	UBERON:0001476	49.24	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
ileal mucosa	UBERON:0000331	49.10	silver quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
oviduct epithelium	UBERON:0004804	48.41	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
metanephric glomerulus	UBERON:0004736	47.74	gold quality
nasal cavity epithelium	UBERON:0005384	47.70	gold quality
renal glomerulus	UBERON:0000074	47.60	gold quality
layer of synovial tissue	UBERON:0007616	47.54	gold quality
kidney epithelium	UBERON:0004819	47.32	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
diaphragm	UBERON:0001103	47.05	gold quality
gluteal muscle	UBERON:0002000	47.03	gold quality
triceps brachii	UBERON:0001509	47.01	gold quality
nephron tubule	UBERON:0001231	46.88	gold quality
skin of hip	UBERON:0001554	45.87	silver quality
metanephros	UBERON:0000081	45.37	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	45.35	gold quality
inferior olivary complex	UBERON:0002127	45.14	gold quality
muscle tissue	UBERON:0002385	44.98	gold quality
skeletal muscle tissue	UBERON:0001134	44.34	gold quality
trachea	UBERON:0003126	43.44	gold quality
squamous epithelium	UBERON:0006914	43.42	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
epithelium of esophagus	UBERON:0001976	42.87	gold quality
epithelium of bronchus	UBERON:0002031	42.82	gold quality
bronchus	UBERON:0002185	42.70	gold quality
colonic epithelium	UBERON:0000397	42.44	gold quality
cartilage tissue	UBERON:0002418	42.04	gold quality
bone marrow cell	CL:0002092	42.00	gold quality
medulla oblongata	UBERON:0001896	41.74	gold quality
upper leg skin	UBERON:0004262	41.50	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
epithelium of mammary gland	UBERON:0003244	41.33	gold quality
dorsal plus ventral thalamus	UBERON:0001897	41.20	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
dorsal root ganglion	UBERON:0000044	40.51	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality
tongue	UBERON:0001723	40.09	gold quality
pleura	UBERON:0000977	40.00	gold quality
mammary duct	UBERON:0001765	39.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality
kidney	UBERON:0002113	39.91	gold quality
saphenous vein	UBERON:0007318	39.83	gold quality
parotid gland	UBERON:0001831	39.81	gold quality
urethra	UBERON:0000057	39.80	gold quality
heart right ventricle	UBERON:0002080	39.79	gold quality
pericardium	UBERON:0002407	39.77	gold quality
male germ cell	CL:0000015	39.75	gold quality
endothelial cell	CL:0000115	39.75	gold quality
synovial joint	UBERON:0002217	39.70	gold quality
nipple	UBERON:0002030	39.68	gold quality
bronchial epithelial cell	CL:0002328	39.65	gold quality
decidua	UBERON:0002450	39.65	gold quality
penis	UBERON:0000989	39.64	gold quality
gingiva	UBERON:0001828	39.64	gold quality
trigeminal ganglion	UBERON:0001675	39.63	gold quality
tendon of biceps brachii	UBERON:0008188	39.60	gold quality
inferior vagus X ganglion	UBERON:0005363	39.57	gold quality
superior surface of tongue	UBERON:0007371	39.56	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.43

HPA expression

RNA tissue specificity: Tissue enriched

4 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Liver	tissue	659.1
Caudate putamen	tissue	0.5
Frontal cortex	tissue	0.3
Kidney	tissue	0.1

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, GABPA, HNF4A, NR2F2

miRNA regulators (miRDB)

Targeting F9 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 88 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-548AZ-3P	99.82	70.56	3549

Functional genomics

Regional missense constraint (gnomAD)

ENST00000218099 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
X:139,530,765–139,537,045	39 / 33.3	1.17	no
X:139,537,046–139,562,068	177 / 311.8	0.57	no
ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Asn346Asp results in dysfunctional protein with defective factor VIIIa interaction. (PMID:11583320)
• Mutations in the factor IX gene (F9) during the past 150 years have relative rates similar to ancient mutations. (PMID:11754103)
• role of EGF-like domains in stimulation by factor VIIIa and it’s isolated A2 domain (PMID:11925427)
• increased procoagulant activity due to formation of additional fVIII phosphatidylserine binding sites on the outer surface of oxLDL-treated cells and higher binding affinity between components of the Xase complex, activated factors VIII and IX. (PMID:12036878)
• Circulating and binding characteristics of human wild-type factor IX and certain Gla domain mutants injected into factor IX-deficient mice in in vivo models and applied to human artery specimens. (PMID:12070021)
• determination of role of EGF1 of activated factor IX in direct binding to activated factor VIII (PMID:12105230)
• a three-dimensional model of the ternary complex between FVIIa:TF:FIX was built using a full-space search algorithm in combination with computational graphics (PMID:12152682)
• Data show that the rate of factor IX activation by factor XIa is not enhanced by biological surfaces, and activated platelet surfaces are thrombogenic while endothelial surfaces are not. (PMID:12167623)
• F9 is activated by interaction with the erythrocyte membrane, causing intrinsic coagulation (PMID:12192300)
• role of factor IX gamma-carboxyglutamic acid domain in interactions between factor IX and factor XIa (PMID:12496253)
• restriction fragment length polymorphisms of FIX gene may be useful markers for carrier detection and prenatal diagnosis in Chinese families with hemophilia B patients (PMID:12513796)
• Low density lipoprotein receptor-related protein and factor IXa share structural requirements for binding to the A3 domain of coagulation factor VIII (PMID:12522143)
• activated coagulation factor IX binds to low density lipoprotein receptor-related protein via residues phe342-asn346 (PMID:12522212)
• A model of the FIXa-FVIIIa complex was constructed and indicated that EGF1 of FIXa does not interact directly with FVIIIa. (PMID:12570162)
• randomly unpredictable amino acid pairs are more sensitive to variants (PMID:12824704)
• the Pro55Ser mutation causes hemophilia primarily through to an impaired ability to activate FX whereas at least in vitro the Pro55Leu defect interferes with the activation of FIX. (PMID:12871416)
• the addition of the cytoplasmic domain of P-selectin to FIX modifies the cellular fate of the FIX molecule by directing the recombinant protein toward regulated-secretory granules without altering its coagulant activity (PMID:12871503)
• high levels of coagulation FXI, FIX and FVIII are related to risk of inherited thrombophilia syndrome (PMID:14521595)
• findings suggest that antithrombin exosites responsible for enhancing the rates of factor Xa and factor IXa inhibition in the conformationally activated inhibitor lie in strand 3 of beta-sheet C of the serpin (PMID:14532267)
• Review. The FXI gene is encodes a 607 AA zymogen for a serine protease. The serine protease domain is similar many other coagulation factors; the heavy chain contains 4 tandem Apple domains. FXI is a homodimer, which essential for normal function. (PMID:14567539)
• FIXa/FVIIIa binding studies of coordinate binding of FVIIIa and FX to equivalent numbers of binding sites on activated platelets provide strong evidence that FVIIIa comprises the receptor that presents FX to FIXa for catalysis on the platelet membrane. (PMID:14629468)
• binding of the factor IX gamma-carboxyglutamic acid domain to the vitamin K-dependent gamma-glutamyl carboxylase active site has a role in carboxylation and regulation of release of carboxylated product (PMID:14660587)
• complex structure shows that the complementarity determining region loops of the 10C12 antibody form a hydrophobic pocket to accommodate the hydrophobic patch of the Gla domain consisting of Leu-6, Phe-9, and Val-10. (PMID:14722079)
• IXabeta functions within the intrinsic Xase complex to activate X and may play a significant role in producing Xa necessary for the procoagulant response following vascular damage (PMID:14963035)
• FIX gene seems to be intact in the derivative 14, the breakpoint may affect an upstream regulatory sequence that subjects the gene to position effect variegation in hemophilia. (PMID:15009460)
• two common intragenic markers (TaqI and XmnI) in Iranian haemophilia B families (PMID:15183040)
• results strongly suggest that chaperone and lectin molecules act in concert to ensure both proper folding of FIXwt and the retention of mutant molecules (PMID:15219198)
• the antithrombin hinge region extension is the activating conformational change for inhibition of factors IXa and Xa (PMID:15326167)
• residues Asn89, Ile90, and Val107 within loops 1 and 2 (Cys88-Cys109) of the EGF2 domain of factor IXa are essential for normal interactions with the platelet surface and for the assembly of the factor X-activating complex on activated platelets (PMID:15328360)
• H-2 (and other) genes control factor IX antibody development in mice. (PMID:15383460)
• Glu555 alters the electrostatic charge around the active site, and would sterically interfere with the interaction between the FXIa site and residues on F9 and antithrombin. FXI-Glu555 is the first reported FXI variant with a defect in FIX activation. (PMID:15456490)
• A proposed model of the interaction of factor IX peptide comprised of amino acids Gly4-Gln11 enables correlation of known hemophilia B mutations of factor IX at Lys5 or Phe9 with impaired phosphatidylserine interaction. (PMID:15581349)
• 2 new point mutations and a new deletion were found in hemophilia B families from northern India. (PMID:15590401)
• EGF-like domains of factor Xa and factor IXa are important for the activation of the factor VII–tissue factor complex (PMID:15634274)
• factor IX binds initially to exosites on the factor XIa heavy chain, followed by interaction at the active site with subsequent bond cleavage (PMID:15829482)
• analysis of missense mutations in two patients with factor XI deficiency (Val271Leu and Tyr351Ser) and one patient with combined factor XI and factor IX deficiency (Phe349Val)[letter] (PMID:15842381)
• analysis of factor IX(a) binding to Rhodnius nitrophorin 2 (PMID:15866866)
• in the presence of Ca2+, phospholipid, and factor VIIIa, binding of Na+ to factor IXa increases its biologic activity (PMID:15913649)
• Ten representative three-dimensional models of the FVIIIa-FIXa complex are presented based on agreements with known experimental data and according to structural criteria. (PMID:16102111)
• Therapeutic levels of human FIX were achieved in nonhuman primates using an adeno-associated virus as a vector for gene therapy of hemophilia B. (PMID:16322469)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	f9b	ENSDARG00000029493
mus_musculus	F9	ENSMUSG00000031138
rattus_norvegicus	F9	ENSRNOG00000003430

Paralogs (16): F7 (ENSG00000057593), F11 (ENSG00000088926), HGFAC (ENSG00000109758), F10 (ENSG00000126218), KLK10 (ENSG00000129451), F12 (ENSG00000131187), C1RL (ENSG00000139178), C1R (ENSG00000159403), KLKB1 (ENSG00000164344), C1S (ENSG00000182326), PRSS55 (ENSG00000184647), CFD (ENSG00000197766), CFI (ENSG00000205403), PRSS51 (ENSG00000253649), HP (ENSG00000257017), HPR (ENSG00000261701)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88384) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 13 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal blood coagulation	5
increased bleeding time	4
hemorrhage	2
decreased hematocrit	1
enlarged spleen	1
internal hemorrhage	1
premature death	1
abnormal wound healing	1
increased susceptibility to induced morbidity/mortality	1
postnatal lethality, incomplete penetrance	1
umbilical cord hemorrhage	1
increased partial thromboplastin time	1
abnormal susceptibility to injury induced morbidity/mortality	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pan troglodytes	Q95ND7	99.8%	Diamond
Pongo abelii	Q5RCB6	99.5%	Diamond
Tropidechis carinatus	P81428	99.3%	Diamond
Notechis scutatus scutatus	P82807	99.3%	Diamond
Pan paniscus	Q2F9P4	98.7%	Diamond
Hoplocephalus stephensii	P83370	97.6%	Diamond
Bos taurus	P00741	96.8%	Diamond
Ovis aries	P16291	96.8%	Diamond
Macaca fascicularis	Q4R577	96.3%	Diamond
Macaca mulatta	Q28520	96.0%	Diamond
Oxyuranus microlepidotus	Q58L95	95.1%	Diamond
Oxyuranus scutellatus	Q58L96	95.1%	Diamond
Pseudonaja textilis	Q1L659	93.6%	Diamond
Capra hircus	Q28315	92.7%	Diamond
Rhinella arenarum	Q66TN7	90.6%	Diamond
Bufo japonicus	Q90WD8	90.6%	Diamond
Felis catus	Q5R1M5	89.9%	Diamond
Canis lupus familiaris	Q867B0	89.9%	Diamond
Sus scrofa	P00772	89.5%	Diamond
Cryptophis nigrescens	B5G6G5	89.2%	Diamond
Acropora millepora	B8V7S0	87.4%	Diamond
Oryctolagus cuniculus	Q28661	86.3%	Diamond
Pseudechis porphyriacus	Q58L93	86.1%	Diamond
Demansia vestigiata	A6MFK7	85.8%	Diamond
Mesocricetus auratus	P15156	84.7%	Diamond
Equus caballus	Q28380	84.7%	Diamond
Macaca nemestrina	Q28858	79.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ATP11C	protein-coding	286410
MCF2	protein-coding	4168
MIR505	ncRNA	574508
FGF13	protein-coding	2258

Protein

Protein identifiers

Coagulation factor IX — P00740 (reviewed: P00740)

Alternative names: Christmas factor, Plasma thromboplastin component

All UniProt accessions (1): P00740

UniProt curated annotations — full annotation on UniProt →

Function. 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.

Subunit / interactions. Heterodimer of a light chain and a heavy chain; disulfide-linked. Interacts (inactive and activated) with F11 (activated) in calcium-dependent manner. Interacts with SERPINC1. Interacts (activated) with iripin-8, a serine protease inhibitor from Ixodes ricinus saliva. Interacts (inactive and activated) with nitrophorin-2, an anticoagulant protein from Rhodnius prolixus.

Subcellular location. Secreted.

Tissue specificity. Detected in blood plasma (at protein level). Synthesized primarily in the liver and secreted in plasma.

Post-translational modifications. Activated by factor XIa, which excises the activation peptide. The propeptide can also be removed by snake venom protease. Activated by coagulation factor VIIa-tissue factor (F7-F3) complex in calcium-dependent manner. The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. Predominantly O-glucosylated at Ser-99 by POGLUT1 in vitro. Carboxylated by vitamin K-dependent GGCX to form gamma-carboxyglutamate; these residues are essential for the binding of calcium.

Disease relevance. Hemophilia B (HEMB) [MIM:306900] An X-linked blood coagulation disorder characterized by a permanent tendency to hemorrhage, due to factor IX deficiency. It is phenotypically similar to hemophilia A, but patients present with fewer symptoms. Many patients are asymptomatic until the hemostatic system is stressed by surgery or trauma. The disease is caused by variants affecting the gene represented in this entry. Mutations in position 43 (Oxford-3, San Dimas) and 46 (Cambridge) prevents cleavage of the propeptide. Mutation in position 93 (Alabama) probably fails to bind to cell membranes. Mutation in position 191 (Chapel-Hill) or in position 226 (Nagoya or Hilo) prevent cleavage of the activation peptide. Thrombophilia, X-linked, due to factor IX defect (THPH8) [MIM:300807] A hemostatic disorder characterized by a tendency to thrombosis. The disease is caused by variants affecting the gene represented in this entry. Warfarin sensitivity, X-linked (WARFS) [MIM:301052] A condition characterized by sensitivity to warfarin, a drugs used as anti-coagulants for the prevention of thromboembolic diseases in subjects with deep vein thrombosis, atrial fibrillation, or mechanical heart valve replacement. Warfarin sensitive individuals develop bleeding complications when they are given warfarin within the therapeutic ranges. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Calcium binds to the gamma-carboxyglutamic acid (Gla) residues in the Gla domain. Calcium can also bind, with stronger affinity, to another site beyond the Gla domain. Under physiological ion concentrations, Ca(2+) is displaced by Mg(2+) from some of the gammaglutamate residues in the N-terminal Gla domain. This leads to a subtle conformation change that may affect the interaction with its binding protein.

Miscellaneous. In 1952, one of the earliest researchers of the disease, Dr. R.G. Macfarlane used the patient’s surname, Christmas, to refer to the disease and also to refer to the clotting factor which he called the ‘Christmas Factor’. At the time, Stephen Christmas was a 5-year-old boy. He died in 1993 at the age of 46 from acquired immunodeficiency syndrome contracted through treatment with blood products.

Similarity. Belongs to the peptidase S1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P00740-1	1	yes
P00740-2	2

RefSeq proteins (2): NP_000124, NP_001300842 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000294	GLA_domain	Domain
IPR000742	EGF	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR012224	Pept_S1A_FX	Family
IPR017857	Coagulation_fac-like_Gla_dom	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR035972	GLA-like_dom_SF	Homologous_superfamily
IPR043504
IPR050442	Peptidase_S1_coag_factors	Family

Pfam: PF00008, PF00089, PF00594, PF14670

Enzyme classification (BRENDA)

• EC 3.4.21.22 — coagulation factor IXa (BRENDA: 3 organisms, 57 substrates, 216 inhibitors, 101 Km, 85 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
FACTOR X	—	79
4-METHYLSULFONYL-D-LEU-GLY-ARG-P-NITROANILIDE	0.5–8.7	8
CH3SO2-D-LEU-GLY-ARG-4-NITROANILIDE	1.7–3.2	6
L-LEU-GLY-L-ARG-4-NITROANILIDE	1.2–2.3	2
CH3SO2-D-LEU-GLY-L-ARG-P-NITROANILIDE	2.3	1
METHOXYCARBONYL-D-NLE-GLY-ARG-P-NITROANILIDE	3.62	1
METHYLSULFONYL-D-CYCLOHEXYLGLYCYL-GLY-ARG-P-NITR	1.43	1
METHYLSULFONYL-D-HEXAHYDROTYROSYL-GLY-ARG-P-NITR	5.99	1

UniProt features (299 total): sequence variant 156, binding site 35, strand 32, modified residue 17, helix 12, disulfide bond 11, turn 8, glycosylation site 8, mutagenesis site 4, domain 4, active site 3, chain 3, propeptide 2, site 2, signal peptide 1, splice variant 1

Structure

Experimental structures (PDB)

showing 30 of 57 structures by resolution:

PDB	Title	Method	Resolution (Å)
5JB9	Crystal structure of factor IXa K98T variant in complex with PPACK	X-RAY DIFFRACTION	1.3
6MV4	CRYSTAL STRUCTURE OF HUMAN COAGULATION FACTOR IXa	X-RAY DIFFRACTION	1.37
5JBA	Crystal structure of factor IXa variant V16I K98T Y177T I212V in complex with PPACK	X-RAY DIFFRACTION	1.4
5TNT	Discovery of novel aminobenzisoxazole derivatives as orally available factor IXa …	X-RAY DIFFRACTION	1.4
4YZU	Rapid development of two Factor IXa inhibitors from Hit to Lead	X-RAY DIFFRACTION	1.41
4Z0K	Rapid development of two Factor IXa inhibitors from Hit to Lead	X-RAY DIFFRACTION	1.41
5JB8	Crystal structure of factor IXa variant K98T in complex with EGR-chloromethylketone	X-RAY DIFFRACTION	1.45
1EDM	EPIDERMAL GROWTH FACTOR-LIKE DOMAIN FROM HUMAN FACTOR IX	X-RAY DIFFRACTION	1.5
2WPH	factor IXa superactive triple mutant	X-RAY DIFFRACTION	1.5
5TNO	Discovery of novel aminobenzisoxazole derivatives as orally available factor IXa …	X-RAY DIFFRACTION	1.54
5JBB	Crystal structure of factor IXa variant V16I K98T Y177T I213V in complex with …	X-RAY DIFFRACTION	1.56
2WPJ	factor IXa superactive triple mutant, NaCl-soaked	X-RAY DIFFRACTION	1.6
6RFK	Crystal structure of EGRCK-inhibited Gla-domainless fIXa (K148Q, R150Q variant)	X-RAY DIFFRACTION	1.6
4WMA	Crystal structure of mouse Xyloside xylosyltransferase 1 complexed with …	X-RAY DIFFRACTION	1.62
3KCG	Crystal structure of the antithrombin-factor IXa-pentasaccharide complex	X-RAY DIFFRACTION	1.7
2WPL	factor IXa superactive triple mutant, EDTA-soaked	X-RAY DIFFRACTION	1.82
5EGM	Development of a novel tricyclic class of potent and selective FIXa inhibitors	X-RAY DIFFRACTION	1.84
4ZAE	Development of a novel class of potent and selective FIXa inhibitors	X-RAY DIFFRACTION	1.86
4WMI	Crystal structure of mouse Xyloside xylosyltransferase 1 complexed with manganese …	X-RAY DIFFRACTION	1.87
8EPH	Crystal structure of human coagulation factor IXa (S195A), apo-form, DES-GLA	X-RAY DIFFRACTION	1.88
3LC3	Benzothiophene Inhibitors of Factor IXa	X-RAY DIFFRACTION	1.9
5F86	Crystal structure of Drosophila Poglut1 (Rumi) complexed with its substrate protein (EGF …	X-RAY DIFFRACTION	1.9
5JBC	Crystal structure of factor IXa variant V16I K98T Y177T I213V in complex with PPACK	X-RAY DIFFRACTION	1.9
4WN2	Crystal structure of mouse Xyloside xylosyltransferase 1 complexed with manganese …	X-RAY DIFFRACTION	1.95
4WNH	Crystal structure of mouse Xyloside xylosyltransferase 1 complexed with …	X-RAY DIFFRACTION	1.95
2WPI	factor IXa superactive double mutant	X-RAY DIFFRACTION	1.99
6X5P	Discovery of Hydroxy Pyrimidine Factor IXa Inhibitors	X-RAY DIFFRACTION	2
2WPM	factor IXa superactive mutant, EGR-CMK inhibited	X-RAY DIFFRACTION	2
4WMB	crystal structure of mouse Xyloside xylosyltransferase 1 complexed with manganese …	X-RAY DIFFRACTION	2.05
4WMK	Crystal structure of mouse Xyloside xylosyltransferase 1 complexed with manganese …	X-RAY DIFFRACTION	2.08

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00740-F1	80.45	0.51

Antibody-complex structures (SAbDab)

4 antibodies co-crystallized with this protein: 1NL0, 7AHV, 8OL9, DENECIMIG

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Serine-type peptidases, Predicted secreted proteins, Plasma proteins, Candidate cardiovascular disease genes, Disease related genes, FDA approved drug targets, Biotech drugs, Human disease related genes

Protein evidence: Evidence at protein level

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (5)

Position	Role
267	charge relay system
315	charge relay system
411	charge relay system
191–192	cleavage; by factor xia
226–227	cleavage; by factor xia

Ligand- & substrate-binding residues (35)

Position	Role
47	Ca(2+)
48	Ca(2+)
53	Ca(2+)
54	Ca(2+)
61	Ca(2+)
61	Mg(2+)
63	Ca(2+)
66	Ca(2+)
66	Mg(2+)
67	Ca(2+)
72	Ca(2+)
72	Mg(2+)
73	Ca(2+)
76	Ca(2+)
76	Mg(2+)
82	Ca(2+)
82	Mg(2+)
86	Ca(2+)
86	Mg(2+)
93	Ca(2+)
94	Ca(2+)
96	Ca(2+)
110	Ca(2+)
111	Ca(2+)
281	Ca(2+)
283	Ca(2+)
286	Ca(2+)
288	Ca(2+)
291	Ca(2+)

Post-translational modifications (17)

Type	Positions
4-carboxyglutamate	53, 54, 61, 63, 66, 67, 72, 73, 76, 79, 82, 86
(3r)-3-hydroxyaspartate	110
Phosphoserine	114, 204
Sulfotyrosine	201
Phosphothreonine	205

Disulfide bonds (11)

Type	Positions
Disulfide bond	64–69, 97–108, 102–117, 119–128, 134–145, 141–155, 157–170, 252–268, 382–396, 407–435
Interchain (between light and heavy chains)	178–335

Glycosylation sites (8)

Type	Positions
O-linked (galnac…) threonine	85, 205, 215, 225
O-linked (glc…) serine	99
O-linked (fuc…) serine	107
N-linked (glcnac…) asparagine	203, 213

Mutagenesis-validated functional residues (4)

Position	Phenotype
305	strongly increases enzyme activity with a synthetic peptide substrate; when associated with t-311; a-365 and t-391.
311	strongly increases enzyme activity with a synthetic peptide substrate; when associated with f-305; a-365 and t-391.
312	strongly decreases enzyme activity with a synthetic peptide substrate.
391	strongly increases enzyme activity with a synthetic peptide substrate; when associated with f-305; t-311 and a-365.

Function

Pathways and Gene Ontology

Reactome pathways

13 curated (TAS) of 27; 10 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

27 pathways:

ID	Pathway	Evidence
R-HSA-9673221	Defective F9 activation ⚕	curated
R-HSA-9673218	Defective F9 secretion ⚕	curated
R-HSA-9673202	Defective F9 variant does not activate FX ⚕	curated
R-HSA-9672396	Defective cofactor function of FVIIIa variant ⚕	curated
R-HSA-9672383	Defective factor IX causes thrombophilia ⚕	curated
R-HSA-9673240	Defective gamma-carboxylation of F9 ⚕	curated
R-HSA-9769743	Amplification and propagation of coagulation cascade	curated
R-HSA-9935598	FXIIa, PKa-dependent activation of coagulation pathway	curated
R-HSA-159740	Gamma-carboxylation of protein precursors	curated
R-HSA-9769735	Initiation of coagulation cascade	curated
R-HSA-9769739	Regulation of clotting cascade	curated
R-HSA-159782	Removal of aminoterminal propeptides from gamma-carboxylated proteins	curated
R-HSA-159763	Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus	curated
R-HSA-9668250	Defective factor IX causes hemophilia B ⚕	—
R-HSA-9662001	Defective factor VIII causes hemophilia A ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-9671793	Diseases of hemostasis ⚕	—
R-HSA-163841	Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	—
R-HSA-159854	Gamma-carboxylation, transport, and amino-terminal cleavage of proteins	—
R-HSA-109582	Hemostasis	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-9629569	Protein hydroxylation	electronic
R-HSA-140834		—
R-HSA-140837		—
R-HSA-140877		—
R-HSA-9651496		—

MSigDB gene sets: 182 (showing top): GOBP_PROTEIN_ACTIVATION_CASCADE, CEBPB_01, GOBP_WOUND_HEALING, GOBP_PROTEIN_MATURATION, REACTOME_GAMMA_CARBOXYLATION_TRANSPORT_AND_AMINO_TERMINAL_CLEAVAGE_OF_PROTEINS, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, HSIAO_LIVER_SPECIFIC_GENES, GOBP_BLOOD_COAGULATION_INTRINSIC_PATHWAY, CAIRO_HEPATOBLASTOMA_DN, BROWN_MYELOID_CELL_DEVELOPMENT_DN, TGGNNNNNNKCCAR_UNKNOWN, REACTOME_INTRINSIC_PATHWAY_OF_FIBRIN_CLOT_FORMATION, GOBP_HEMOSTASIS, BIOCARTA_INTRINSIC_PATHWAY, GOBP_REGULATION_OF_BODY_FLUID_LEVELS

GO Biological Process (4): proteolysis (GO:0006508), blood coagulation (GO:0007596), zymogen activation (GO:0031638), hemostasis (GO:0007599)

GO Molecular Function (8): endopeptidase activity (GO:0004175), serine-type endopeptidase activity (GO:0004252), calcium ion binding (GO:0005509), metal ion binding (GO:0046872), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (6): extracellular region (GO:0005576), endoplasmic reticulum lumen (GO:0005788), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Defective factor IX causes hemophilia B	4
Gamma-carboxylation, transport, and amino-terminal cleavage of proteins	3
Coagulation pathway	3
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	2
Defects of Coagulation cascade	1
Defective factor VIII causes hemophilia A	1
Regulation of clotting cascade	1
Post-translational protein modification	1

GO top-level categories

24 GO namespaces:

Category	Terms
peptidase activity	2
intracellular organelle lumen	2
protein metabolic process	1
hemostasis	1
wound healing	1
coagulation	1
protein processing	1
regulation of body fluid levels	1
endopeptidase activity	1
serine-type peptidase activity	1
metal ion binding	1
cation binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
serine hydrolase activity	1
catalytic activity	1
cellular anatomical structure	1
endoplasmic reticulum	1
Golgi apparatus	1
membrane	1
cell periphery	1
external encapsulating structure	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 19 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
blood coagulation	BP	direct assay
proteolysis	BP	direct assay
zymogen activation	BP	direct assay
extracellular exosome	CC	high-throughput assay
extracellular matrix	CC	high-throughput assay
calcium ion binding	MF	direct assay
endopeptidase activity	MF	direct assay
metal ion binding	MF	experiment

Protein interactions and networks

STRING

showing 16 of 1,206 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
F9	F3	P13726	958
F9	F8	P00451	941
F9	GGCX	P38435	829
F9	VKORC1	Q9BQB6	761
F9	VWF	P04275	741
F9	SERPINC1	P01008	718
F9	ATP11C	Q8NB49	692
F9	IDS	P22304	678
F9	TFPI	P10646	676
F9	THBD	P07204	670
F9	F11	P03951	624
F9	EGF	P01133	605
F9	F7	P08709	595
F9	PROCR	Q9UNN8	572
F9	KNG1	P01042	570
F9	ALB	P02768	570

IntAct

Human interaction partners of F9 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
F8	direct interaction	0.540	2
UBR5	association	0.530	1
SERPINC1	direct interaction	0.440	1
APBB1	association	0.350	1
DDX11L8	association	0.350	1

BioGRID (64 interactions; top human partners by supporting records): ACOT9 (Affinity Capture-MS; 2 records), CBWD1 (Affinity Capture-MS; 2 records), DCP2 (Affinity Capture-MS; 2 records), DSCC1 (Affinity Capture-MS; 2 records), EOGT (Affinity Capture-MS; 2 records), FERMT2 (Affinity Capture-MS; 2 records), HDAC3 (Affinity Capture-MS; 2 records), HELLS (Affinity Capture-MS; 2 records), HOXD13 (Affinity Capture-MS; 2 records), LMLN (Affinity Capture-MS; 2 records), LRP5 (Affinity Capture-MS; 2 records), MCM8 (Affinity Capture-MS; 2 records), MIB2 (Affinity Capture-MS; 2 records), MSTO1 (Affinity Capture-MS; 2 records), POGLUT1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 8 of 20 signaling interactions:

A	Effect	B	Mechanism
CEBPA	“up-regulates quantity by expression”	F9	“transcriptional regulation”
F9	“up-regulates activity”	F7	cleavage
F11	“up-regulates activity”	F9	cleavage
“Factor FVIIa:TF”	“up-regulates activity”	F9	binding
F7	“up-regulates activity”	F9	binding
GGCX	“up-regulates activity”	F9	carboxylation
F9	“form complex”	“Factor VIIIa-IXa”	binding
SERPINC1	“down-regulates activity”	F9	cleavage

Disease & clinical

Genetic variants

Variant evidence for F9: 713 ClinVar records (317 pathogenic / likely pathogenic); 76 ClinGen expert-panel interpretations; 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

713 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	206
Likely pathogenic	111
Uncertain significance	134
Likely benign	179
Benign	38

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 317 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
10607	NM_000133.4(F9):c.1025C>T (p.Thr342Met)	Pathogenic	reviewed by expert panel	15
216926	NM_000133.4(F9):c.835G>A (p.Ala279Thr)	Pathogenic	reviewed by expert panel	14
10602	NM_000133.4(F9):c.881G>A (p.Arg294Gln)	Pathogenic	reviewed by expert panel	12
10579	NM_000133.4(F9):c.316G>A (p.Gly106Ser)	Pathogenic	reviewed by expert panel	11
10585	NM_000133.4(F9):c.572G>A (p.Arg191His)	Pathogenic	reviewed by expert panel	11
10573	NM_000133.4(F9):c.224G>A (p.Arg75Gln)	Pathogenic	reviewed by expert panel	10
10587	NM_000133.4(F9):c.880C>T (p.Arg294Ter)	Pathogenic	reviewed by expert panel	8
10572	NM_000133.4(F9):c.223C>T (p.Arg75Ter)	Pathogenic	reviewed by expert panel	7
627180	NM_000133.4(F9):c.520+13A>G	Pathogenic	reviewed by expert panel	5
811512	NM_000133.4(F9):c.1304G>A (p.Cys435Tyr)	Pathogenic	reviewed by expert panel	3
10624	NM_000133.4(F9):c.1324G>A (p.Gly442Arg)	Pathogenic	reviewed by expert panel	2
626950	NM_000133.4(F9):c.1009G>A (p.Ala337Thr)	Pathogenic	reviewed by expert panel	2
627155	NM_000133.4(F9):c.88+1G>A	Pathogenic	reviewed by expert panel	2
810867	NM_000133.4(F9):c.720G>A (p.Trp240Ter)	Pathogenic	reviewed by expert panel	2
994410	NM_000133.4(F9):c.277G>A (p.Asp93Asn)	Pathogenic	reviewed by expert panel	2

Per-variant reference — Sugi Variant

Explore F9’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

ClinGen expert-panel interpretations (76)

Expert ACMG interpretations from Coagulation Factor Deficiency VCEP for hemophilia B — a higher-authority tier than individual ClinVar submissions.

Assertion	Variants
Pathogenic	28
Likely Pathogenic	22
Uncertain Significance	8
Likely Benign	4
Benign	14

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 614):

Position(s)	Effect	Δscore	Sites
X:139537008–139537009	acceptor_loss	1.0000	6
X:139560856–139560857	donor_loss	1.0000	5
X:139561522–139561523	acceptor_loss	1.0000	5
X:139537004	acceptor_gain	0.9900
X:139537174–139537175	donor_loss	0.9900	5
X:139537178	donor_loss	0.9900	2
X:139551060–139551061	acceptor_loss	0.9900	6
X:139560739–139560740	acceptor_loss	0.9900	6
X:139560857	donor_loss	0.9900
X:139561520	acceptor_gain	0.9900

AlphaMissense

834 missense substitutions predicted likely pathogenic (of 3,048 scored), across 205 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D315	8	0.975	0.992
D410	8	0.971	0.990
D405	8	0.939	0.982
S411	8	0.907	0.985
S430	8	0.905	0.996
H267	8	0.886	0.946
M394	8	0.768	0.881
C396	7	0.993	0.997
C407	7	0.992	0.997
C382	7	0.989	0.994
C108	7	0.988	0.996
C268	7	0.988	0.993
C102	7	0.986	0.994
C128	7	0.986	0.994
C252	7	0.985	0.992
C335	7	0.983	0.989
C117	7	0.982	0.993
C64	7	0.981	0.995
C435	7	0.981	0.994
C97	7	0.979	0.994

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Liver Hepatocellular Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	favorable	3.31e-05

Disease associations

OMIM: gene MIM:300746 | disease phenotypes: MIM:306900, MIM:300807, MIM:134500, MIM:306700

GenCC curated gene-disease

6 curated gene-disease records:

Disease	Classification	Inheritance	Records
hemophilia B	Definitive	X-linked recessive	3
thrombophilia, X-linked, due to factor 9 defect	Strong	X-linked	2
severe hemophilia B	Supportive	X-linked
moderately severe hemophilia B	Supportive	X-linked
mild hemophilia B	Supportive	X-linked
symptomatic form of hemophilia B in female carriers	Supportive	X-linked

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

2 validity classifications:

Disease	Classification	Inheritance
hemophilia B	Definitive	XL
thrombophilia, X-linked, due to factor 9 defect	Limited	XL

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (3 panels, 3 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

3 panels:

Panel	Rating
Bleeding and platelet disorders	green
Factor IX deficiency	green
Inherited bleeding disorders	green

Mondo (8): hemophilia B leyden (MONDO:0850054), hemophilia B (MONDO:0010604), thrombophilia, X-linked, due to factor 9 defect (MONDO:0010432), hemophilia A (MONDO:0010602), moderately severe hemophilia B (MONDO:0015716), severe hemophilia B (MONDO:0015715), mild hemophilia B (MONDO:0015717), symptomatic form of hemophilia B in female carriers (MONDO:0015788)

Orphanet (4): Hemophilia B Leyden (Orphanet:617930), Hemophilia B (Orphanet:98879), Hemophilia A (Orphanet:98878), Moderate hemophilia B (Orphanet:169796)

HPO phenotypes

18 phenotypes (HPO-id order):

HPO	Term
HP:0000421	Epistaxis
HP:0000790	Hematuria
HP:0000967	Petechiae
HP:0000978	Bruising susceptibility
HP:0001419	X-linked recessive inheritance
HP:0001934	Persistent bleeding after trauma
HP:0002239	Gastrointestinal hemorrhage
HP:0002248	Hematemesis
HP:0002249	Melena
HP:0002625	Deep venous thrombosis
HP:0002758	Osteoarthritis
HP:0003645	Prolonged partial thromboplastin time
HP:0005261	Joint hemorrhage
HP:0005542	Prolonged whole-blood clotting time
HP:0008151	Prolonged prothrombin time
HP:0011858	Reduced factor IX activity
HP:0033061	Increased factor IX activity
HP:0100724	Hypercoagulability

GWAS associations

1 associations:

Study	Trait	p-value
GCST009097_17	Venous thromboembolism	3e-17

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D006467	Hemophilia A	C15.378.100.100.500; C15.378.100.141.500; C15.378.463.500; C16.320.099.500
D002836	Hemophilia B	C15.378.100.100.510; C15.378.100.141.510; C15.378.463.510; C16.320.099.510; C16.320.322.235
C567581	Thrombophilia, X-Linked, Due To Factor Ix Defect *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2016 (SINGLE PROTEIN), CHEMBL2111424 (SELECTIVITY GROUP), CHEMBL4296076 (PROTEIN COMPLEX)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the F9 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

11 curated-mechanism drugs:

Drug	Modality	Max phase
ALBUTREPENONACOG ALFA	Protein	4
COAGULATION FACTOR IX HUMAN	Unknown	4
COAGULATION FACTOR IX RECOMBINANT HUMAN	Protein	4
EFTRENONACOG ALFA	Protein	4
ETRANACOGENE DEZAPARVOVEC	Gene	4
FIDANACOGENE ELAPARVOVEC	Gene	4
NONACOG BETA PEGOL	Protein	4
VALOCTOCOGENE ROXAPARVOVEC	Gene	4
PEGNIVACOGIN	Unknown	3
PROTHROMBIN COMPLEX CONCENTRATE	Protein	3
TRENONACOG ALFA	Unknown	3

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes F9 — the drug acts on the assembly or class, not necessarily on this subunit alone.

1 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
EMICIZUMAB	Coagulation factor IX and X	2	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 699 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

2 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1095032	LETAXABAN	2	390
CHEMBL206335	RAZAXABAN	2	309

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — S1: Chymotrypsin

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 57 [PMID: 20121197]	Inhibition	8.7	pIC50
emicizumab	Binding	5.8	pKd

Binding affinities (BindingDB)

932 measured of 1118 human assays (1120 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
methyl N-[(10R,14S)-14-[4-(3-chloro-6-cyano-2-fluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.03 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-[3-chloro-6-(difluoromethoxy)-2-fluorophenyl]-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,18-diazatricyclo[13.3.1.02,7]nonadeca-1(18),2(7),3,5,15(19),16-hexaen-5-yl]carbamate	KI	0.04 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
(10R,14S)-14-[4-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2,4,6,15,17-hexaen-9-one	KI	0.05 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-17-chloro-14-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.05 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-[3-chloro-6-(difluoromethoxy)-2-fluorophenyl]-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.06 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
(13R,17S)-17-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-6,13-dimethyl-12-oxo-7,11,19-triazatetracyclo[16.3.1.02,10.04,8]docosa-1(22),2(10),3,5,8,18,20-heptaene-5-carboxylic acid	KI	0.06 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
(10R,14S)-14-[4-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]-6-oxo-2,3-dihydropyridin-1-yl]-4,5-difluoro-10-methyl-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2,4,6,15,17-hexaen-9-one	KI	0.07 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
2-[(2-methylpropan-2-yl)oxy]ethyl N-[(10R,14S)-14-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.08 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
2-hydroxyethyl N-[(10R,14S)-14-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.08 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-(3-chloro-6-cyano-2-fluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-17-methoxy-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.09 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-[5-chloro-2-(trifluoromethyl)phenyl]-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.09 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
(10S,14S)-14-[4-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]-6-oxo-2,3-dihydropyridin-1-yl]-10-propan-2-yl-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2,4,6,15,17-hexaen-9-one	KI	0.09 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-(6-cyano-2-fluoro-3-methylphenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.09 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-[3-chloro-2-fluoro-6-(trifluoromethyl)phenyl]-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.1 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-(3-chloro-6-ethynyl-2-fluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.1 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-[3-chloro-2-fluoro-6-(2H-triazol-4-yl)phenyl]-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.11 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-[5-chloro-2-(difluoromethoxy)phenyl]-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.13 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
1-[3-(Aminomethyl)phenyl]-N-[3-fluoro-2-(methylsulfonyl)-[1,1-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide	KI	0.15 nM
methyl N-[(10R,14S)-14-[4-(3-chloro-6-cyano-2-fluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,18-diazatricyclo[13.3.1.02,7]nonadeca-1(18),2(7),3,5,15(19),16-hexaen-5-yl]carbamate	KI	0.15 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-(6-acetyl-3-chloro-2-fluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8-azatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.17 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10S,14S)-14-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-11-fluoro-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.18 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10,17-dimethyl-9-oxo-8,16,18-triazatricyclo[13.2.1.02,7]octadeca-1(17),2(7),3,5,15(18)-pentaen-5-yl]carbamate	KI	0.2 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-(3-chloro-6-cyano-2-fluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9,17-dioxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-2(7),3,5-trien-5-yl]carbamate	KI	0.21 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-(3-chloro-2-fluoro-6-methylphenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.23 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-(6-acetyl-3-chloro-2-fluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-17-fluoro-10-methyl-9-oxo-8-azatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.23 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-(3-bromo-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.27 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
(14R,18S)-18-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-14-methyl-8,12,20-triazatetracyclo[17.3.1.02,11.04,9]tricosa-1(23),2,5,9,11,19,21-heptaene-7,13-dione	KI	0.31 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-(6-bromo-2-fluoro-3-methylphenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.38 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-(3-chloro-6-cyano-2-fluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8-azatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.42 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
(10R,14S)-14-[4-[3-chloro-2-fluoro-6-(trifluoromethyl)phenyl]-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaene-4-carboxylic acid	KI	0.44 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
ethyl 2-[5-[[(10R,14S)-14-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]amino]-1,3,4-oxadiazol-2-yl]acetate	KI	0.45 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
(10R,14S)-14-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-5-[(5-methyl-1,3,4-oxadiazol-2-yl)amino]-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-9-one	KI	0.46 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
(10R,14S)-14-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-5-(pyridin-3-ylamino)-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-9-one	KI	0.47 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
(7S)-7-[[2-chloro-4-(1-methyl-5-oxo-1,2,4-triazol-4-yl)benzoyl]amino]-7-(3-fluorophenyl)-2-methyl-8,9-dihydro-6H-pyrido[1,2-a]indole-10-carboxylic acid	IC50	0.509 nM	US-10351558: Factor IXa inhibitors
methyl N-[(10R,14S)-14-[4-(3-chloro-6-cyano-2-fluorophenyl)-6-oxopyridazin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.55 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
(10R,14S)-5-amino-14-[4-(3-chloro-2,6-difluorophenyl)-2-oxo-1-pyridinyl]-10-methyl-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-9-one	KI	0.56 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
(10R,14S)-14-[4-(3-chloro-2,6-difluorophenyl)-2-oxo-1-pyridinyl]-10-methyl-5-(pyrimidin-2-ylamino)-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-9-one	KI	0.56 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
methyl N-[(10R,14S)-14-[4-(6-bromo-3-chloro-2-fluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8-azatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.59 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
(7S)-2-methyl-7-phenyl-7-[[4-(1,2,4-triazol-4-yl)benzoyl]amino]-8,9-dihydro-6H-pyrido[1,2-a]indole-10-carboxylic acid	IC50	0.596 nM	US-10351558: Factor IXa inhibitors
CHEMBL3629114	KI	0.6 nM
methyl N-[(10R,14S)-14-[4-(5-chloro-2-methylphenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.62 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
(7S)-7-[[2-chloro-4-(3-methoxy-1,2,4-triazol-1-yl)benzoyl]amino]-2-methyl-7-phenyl-8,9-dihydro-6H-pyrido[1,2-a]indole-10-carboxylic acid	IC50	0.636 nM	US-10351558: Factor IXa inhibitors
(10R,14S)-14-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-5-[(5-cyclopropyl-1,3,4-oxadiazol-2-yl)amino]-10-methyl-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-9-one	KI	0.67 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
(10R,14S)-14-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-5-[[5-(methoxymethyl)-1,3,4-oxadiazol-2-yl]amino]-10-methyl-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-9-one	KI	0.69 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
(14R,18S)-18-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-14-methyl-8,12,20-triazatetracyclo[17.3.1.02,11.04,9]tricosa-1(23),2(11),3,9,19,21-hexaene-7,13-dione	KI	0.72 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
(7S)-7-[[2-chloro-4-(3-methyl-1,2,4-triazol-1-yl)benzoyl]amino]-7-(3-fluorophenyl)-2-methyl-8,9-dihydro-6H-pyrido[1,2-a]indole-10-carboxylic acid	IC50	0.791 nM	US-10351558: Factor IXa inhibitors
methyl N-[(10R,14S)-14-[4-(3-chloro-2,6-difluorophenyl)-3-methyl-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-5-yl]carbamate	KI	0.8 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
(10R,14S)-14-[4-(3-chloro-2,6-difluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-5-(pyridazin-3-ylamino)-8,16-diazatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaen-9-one	KI	0.8 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors
CHEMBL3628964	KI	0.8 nM
(10R,14S)-14-[4-(6-bromo-3-chloro-2-fluorophenyl)-6-oxo-2,3-dihydropyridin-1-yl]-10-methyl-9-oxo-8-azatricyclo[13.3.1.02,7]nonadeca-1(19),2(7),3,5,15,17-hexaene-4-carboxylic acid	KI	0.81 nM	US-9409908: Dihydropyridone p1 as factor XIa inhibitors

ChEMBL bioactivities

940 potent at pChembl≥5 of 976 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.52	Ki	0.03	nM	CHEMBL4107149
10.40	Ki	0.04	nM	CHEMBL4110926
10.30	Ki	0.05	nM	CHEMBL4112773
10.30	Ki	0.05	nM	CHEMBL4114881
10.22	Ki	0.06	nM	CHEMBL4113483
10.22	Ki	0.06	nM	CHEMBL4109568
10.15	Ki	0.07	nM	CHEMBL4108033
10.10	Ki	0.08	nM	CHEMBL4115630
10.10	Ki	0.08	nM	CHEMBL4110983
10.05	Ki	0.09	nM	CHEMBL4111429
10.05	Ki	0.09	nM	CHEMBL4106708
10.05	Ki	0.09	nM	CHEMBL3948120
10.05	Ki	0.09	nM	CHEMBL4113824
10.00	Ki	0.1	nM	CHEMBL4114933
10.00	Ki	0.1	nM	CHEMBL4107808
9.96	Ki	0.11	nM	CHEMBL4115423
9.89	Ki	0.13	nM	CHEMBL4110346
9.82	Ki	0.15	nM	CHEMBL4110901
9.77	Ki	0.17	nM	CHEMBL4107795
9.74	Ki	0.18	nM	CHEMBL4115353
9.70	Ki	0.2	nM	CHEMBL4112648
9.68	Ki	0.21	nM	CHEMBL4114611
9.64	Ki	0.23	nM	CHEMBL4114880
9.64	Ki	0.23	nM	CHEMBL4112546
9.57	Ki	0.27	nM	CHEMBL4112357
9.51	Ki	0.31	nM	CHEMBL4109665
9.42	Ki	0.38	nM	CHEMBL4111371
9.38	Ki	0.42	nM	CHEMBL4112342
9.36	Ki	0.44	nM	CHEMBL4106934
9.35	Ki	0.45	nM	CHEMBL4107368
9.34	Ki	0.46	nM	CHEMBL4112597
9.33	Ki	0.47	nM	CHEMBL4111663
9.29	IC50	0.509	nM	CHEMBL5915125
9.26	Ki	0.55	nM	CHEMBL4109580
9.25	Ki	0.56	nM	CHEMBL4112483
9.25	Ki	0.56	nM	CHEMBL4111142
9.23	Ki	0.59	nM	CHEMBL4111308
9.22	Ki	0.6	nM	CHEMBL3629111
9.22	Ki	0.6	nM	CHEMBL3629114
9.22	IC50	0.596	nM	CHEMBL5780078
9.21	Ki	0.62	nM	CHEMBL4113149
9.20	IC50	0.636	nM	CHEMBL5743170
9.17	Ki	0.67	nM	CHEMBL4114332
9.16	Ki	0.69	nM	CHEMBL4115130
9.14	Ki	0.72	nM	CHEMBL4114872
9.10	Ki	0.8	nM	CHEMBL3628964
9.10	Ki	0.8	nM	CHEMBL4112921
9.10	Ki	0.8	nM	CHEMBL4113427
9.10	IC50	0.791	nM	CHEMBL5782236
9.09	Ki	0.81	nM	CHEMBL4113230

PubChem BioAssay actives

393 with measured affinity, of 706 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(7S)-7-[[2-chloro-4-(1,2,4-triazol-4-yl)benzoyl]amino]-2-methyl-7-phenyl-8,9-dihydro-6H-pyrido[1,2-a]indole-10-carboxylic acid	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0006	uM
(7S)-7-[[2,6-dichloro-4-(3-methyl-1,2,4-triazol-1-yl)benzoyl]amino]-2-methyl-7-phenyl-8,9-dihydro-6H-pyrido[1,2-a]indole-10-carboxylic acid	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0006	uM
(E)-3-[(7S)-7-[[2,6-dichloro-4-(1,2,4-triazol-4-yl)benzoyl]amino]-2-methyl-7-phenyl-8,9-dihydro-6H-pyrido[1,2-a]indol-10-yl]prop-2-enoic acid	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0008	uM
2,6-dichloro-N-[(2R)-2-(8-fluoro-5-methyl-4-oxo-3H-quinazolin-2-yl)-2-(3-fluorophenyl)ethyl]-4-(3-methyl-1,2,4-triazol-1-yl)benzamide	1252147: Inhibition of human coagulation factor 9a using fluorescent peptide CH3SO2-D-CHG-Gly-Arg-AFC-AcoH as substrate	ki	0.0010	uM
(7S)-7-[[2,6-dichloro-4-(1,2,4-triazol-4-yl)benzoyl]amino]-2-methyl-7-phenyl-8,9-dihydro-6H-pyrido[1,2-a]indole-10-carboxamide	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0012	uM
N-[(7S)-10-(5-amino-3-pyridinyl)-2-methyl-7-phenyl-8,9-dihydro-6H-pyrido[1,2-a]indol-7-yl]-2,6-dichloro-4-(1,2,4-triazol-4-yl)benzamide	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0016	uM
2,6-dichloro-N-[(2R)-8-methyl-2-(3-methylphenyl)-3,4-dihydro-1H-pyrido[1,2-b]indazol-2-yl]-4-(3-methyl-1,2,4-triazol-1-yl)benzamide	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0018	uM
2,6-dichloro-N-[(2R)-2-(3-fluoro-4-hydroxyphenyl)-2-(2-methyl-3H-benzimidazol-5-yl)ethyl]-4-(3-methyl-1,2,4-triazol-1-yl)benzamide	1283907: Inhibition of human factor 9a using CH3SO2-DCHG-Gly-Arg-AFC.AcOH as substrate preinubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence assay	ic50	0.0019	uM
[2-[(2-carbamimidoyl-1-benzothiophen-4-yl)oxy]-2-phenylethyl] N-[2-[(2-methylpropylamino)methyl]phenyl]carbamate	459562: Inhibition of human recombinant factor 9a by amidolytic assay	ki	0.0020	uM
2-chloro-N-[(2R)-8-methyl-2-(3-methylphenyl)-3,4-dihydro-1H-pyrido[1,2-b]indazol-2-yl]-4-(3-methyl-1,2,4-triazol-1-yl)benzamide	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0021	uM
2,6-dichloro-N-[(7S)-10-[(E)-hydroxyiminomethyl]-2-methyl-7-phenyl-8,9-dihydro-6H-pyrido[1,2-a]indol-7-yl]-4-(1,2,4-triazol-4-yl)benzamide	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0024	uM
2,6-dichloro-N-[(7S)-2-methyl-7-phenyl-10-(2H-tetrazol-5-yl)-8,9-dihydro-6H-pyrido[1,2-a]indol-7-yl]-4-(1,2,4-triazol-4-yl)benzamide	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0024	uM
(7S)-7-[[3-chloro-5-(1,2,4-triazol-4-yl)pyridine-2-carbonyl]amino]-2-methyl-7-phenyl-8,9-dihydro-6H-pyrido[1,2-a]indole-10-carboxylic acid	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0025	uM
(7S)-7-[[2-chloro-4-(1,2,4-triazol-4-yl)benzoyl]amino]-2-methyl-7-phenyl-8,9-dihydro-6H-pyrido[1,2-a]indole-10-carboxamide	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0026	uM
3-[(7S)-7-[[2-chloro-4-(3-methyl-1,2,4-triazol-1-yl)benzoyl]amino]-2-methyl-7-phenyl-8,9-dihydro-6H-pyrido[1,2-a]indol-10-yl]propanoic acid	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0027	uM
2,6-dichloro-N-[(2R)-2-(6-chloro-5-methoxy-1H-benzimidazol-2-yl)-2-(3-fluorophenyl)ethyl]-4-(3-methyl-1,2,4-triazol-1-yl)benzamide	1252147: Inhibition of human coagulation factor 9a using fluorescent peptide CH3SO2-D-CHG-Gly-Arg-AFC-AcoH as substrate	ki	0.0029	uM
2-[(7S)-7-[[2,6-dichloro-4-(1,2,4-triazol-4-yl)benzoyl]amino]-2-methyl-7-phenyl-8,9-dihydro-6H-pyrido[1,2-a]indol-10-yl]acetic acid	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0029	uM
2-chloro-N-[(2R)-2-(3-methoxyphenyl)-8-methyl-3,4-dihydro-1H-pyrido[1,2-b]indazol-2-yl]-4-(3-methyl-1,2,4-triazol-1-yl)benzamide	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0030	uM
[2-[(2-carbamimidoyl-1-benzothiophen-4-yl)oxy]-2-phenylethyl] N-[2-(piperazin-1-ylmethyl)phenyl]carbamate	459562: Inhibition of human recombinant factor 9a by amidolytic assay	ki	0.0030	uM
[2-[(2-carbamimidoyl-1-benzothiophen-4-yl)oxy]-2-phenylethyl] N-[1,3-dimethyl-5-[(propan-2-ylamino)methyl]pyrazol-4-yl]carbamate	459562: Inhibition of human recombinant factor 9a by amidolytic assay	ki	0.0030	uM
methyl 2-[3-(2-carbamimidoyl-1-benzothiophen-5-yl)phenoxy]-2-thiophen-2-ylacetate	459575: Inhibition of human recombinant factor 9a by amidolytic assay	ki	0.0030	uM
[(2R)-2-[(2-carbamimidoyl-1-benzothiophen-4-yl)oxy]-2-phenylethyl] N-(4-methoxyphenyl)carbamate	459562: Inhibition of human recombinant factor 9a by amidolytic assay	ki	0.0030	uM
[2-[(2-carbamimidoyl-1-benzothiophen-4-yl)oxy]-2-phenylethyl] N-[2-(methylaminomethyl)phenyl]carbamate	459562: Inhibition of human recombinant factor 9a by amidolytic assay	ki	0.0030	uM
2,6-dichloro-N-[(2R)-2-(3-chlorophenyl)-8-methyl-3,4-dihydro-1H-pyrido[1,2-b]indazol-2-yl]-4-(3-methyl-1,2,4-triazol-1-yl)benzamide	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0031	uM
2,6-dichloro-N-[(2R)-2-(8-fluoro-5-methyl-4-oxo-1H-quinolin-2-yl)-2-(3-fluorophenyl)ethyl]-4-(3-methyl-1,2,4-triazol-1-yl)benzamide	1252147: Inhibition of human coagulation factor 9a using fluorescent peptide CH3SO2-D-CHG-Gly-Arg-AFC-AcoH as substrate	ki	0.0033	uM
1-[3-chloro-4-[(10-hydroxy-2,7-dimethyl-3,4-dihydro-1H-pyrido[1,2-b]indazol-2-yl)carbamoyl]phenyl]benzimidazole-5-carboxylic acid	1393328: Inhibition of recombinant human factor 9a	ki	0.0035	uM
2,6-dichloro-N-[(2R)-2-(5,6-dimethyl-1H-benzimidazol-2-yl)-2-phenylethyl]-4-(1,2,4-triazol-4-yl)benzamide	1252147: Inhibition of human coagulation factor 9a using fluorescent peptide CH3SO2-D-CHG-Gly-Arg-AFC-AcoH as substrate	ki	0.0036	uM
2,6-dichloro-N-[(2S)-2-(3-fluorophenyl)-2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)ethyl]-4-(3-methyl-1,2,4-triazol-1-yl)benzamide	1252147: Inhibition of human coagulation factor 9a using fluorescent peptide CH3SO2-D-CHG-Gly-Arg-AFC-AcoH as substrate	ki	0.0037	uM
[2-[(2-carbamimidoyl-1-benzothiophen-4-yl)oxy]-2-phenylethyl] N-[2-(aminomethyl)phenyl]carbamate	459562: Inhibition of human recombinant factor 9a by amidolytic assay	ki	0.0040	uM
[2-[(2-carbamimidoyl-1-benzothiophen-4-yl)oxy]-2-phenylethyl] N-[4-[2-(dimethylamino)ethoxy]phenyl]carbamate	459562: Inhibition of human recombinant factor 9a by amidolytic assay	ki	0.0040	uM
2,6-dichloro-N-[(2R)-2-(4-fluorophenyl)-8-methyl-3,4-dihydro-1H-pyrido[1,2-b]indazol-2-yl]-4-(3-methyl-1,2,4-triazol-1-yl)benzamide	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0042	uM
1-(3-carbamimidoylphenyl)-N-[4-(5-chlorobenzimidazol-1-yl)-2-fluorophenyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	1796940: Enzyme Assay and Determination of the Inhibition Constants. from Article 10.1016/j.bmcl.2004.08.034: “SAR and factor IXa crystal structure of a dual inhibitor of factors IXa and Xa.”	ki	0.0042	uM
[2-[(2-carbamimidoyl-6-fluoro-1-benzothiophen-4-yl)oxy]-2-phenylethyl] N-[2-(aminomethyl)phenyl]carbamate	459562: Inhibition of human recombinant factor 9a by amidolytic assay	ki	0.0044	uM
2,6-dichloro-4-(3-methyl-1,2,4-triazol-1-yl)-N-[(2R)-8-methyl-2-[3-(trifluoromethyl)phenyl]-3,4-dihydro-1H-pyrido[1,2-b]indazol-2-yl]benzamide	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0045	uM
2-chloro-N-[(1R,4S,7S)-2-(4-chloro-[1,2]oxazolo[5,4-c]pyridin-7-yl)-2-azabicyclo[2.2.1]heptan-7-yl]-4-(3-methyl-1,2,4-triazol-1-yl)benzamide	1450166: Inhibition of human coagulation factor 9a using SPECTROFLUOR F9a as substrate after 60 mins by fluorescence assay	ic50	0.0049	uM
2,6-dichloro-N-[(2R)-8-methyl-2-(1-propan-2-yltriazol-4-yl)-3,4-dihydro-1H-pyrido[1,2-b]indazol-2-yl]-4-(3-methyl-1,2,4-triazol-1-yl)benzamide	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0050	uM
[2-[(2-carbamimidoyl-1-benzothiophen-4-yl)oxy]-2-phenylethyl] N-[1-methyl-3-(methylaminomethyl)pyrazol-5-yl]carbamate	459562: Inhibition of human recombinant factor 9a by amidolytic assay	ki	0.0050	uM
[2-[(2-carbamimidoyl-1-benzothiophen-4-yl)oxy]-2-phenylethyl] N-[1,3-dimethyl-5-(methylaminomethyl)pyrazol-4-yl]carbamate	459562: Inhibition of human recombinant factor 9a by amidolytic assay	ki	0.0050	uM
[2-[(2-carbamimidoyl-1-benzothiophen-4-yl)oxy]-2-phenylethyl] N-(2-fluorophenyl)carbamate	459562: Inhibition of human recombinant factor 9a by amidolytic assay	ki	0.0050	uM
[2-[(2-carbamimidoyl-1-benzothiophen-4-yl)oxy]-2-phenylethyl] N-(4-methoxyphenyl)carbamate	459562: Inhibition of human recombinant factor 9a by amidolytic assay	ki	0.0050	uM
2,6-dichloro-N-[(7S)-10-cyano-2-methyl-7-phenyl-8,9-dihydro-6H-pyrido[1,2-a]indol-7-yl]-4-(1,2,4-triazol-4-yl)benzamide	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0051	uM
1-(3-carbamimidoylphenyl)-N-[4-(6-chlorobenzimidazol-1-yl)-2-fluorophenyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	1796940: Enzyme Assay and Determination of the Inhibition Constants. from Article 10.1016/j.bmcl.2004.08.034: “SAR and factor IXa crystal structure of a dual inhibitor of factors IXa and Xa.”	ki	0.0051	uM
2,6-dichloro-N-[(7S)-2-methyl-7-phenyl-10-(2,2,2-trifluoro-1-hydroxyethyl)-8,9-dihydro-6H-pyrido[1,2-a]indol-7-yl]-4-(1,2,4-triazol-4-yl)benzamide	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0055	uM
N-[4-(benzimidazol-1-yl)phenyl]-1-(3-carbamimidoylphenyl)-3-pyridin-3-ylpyrazole-5-carboxamide	1796940: Enzyme Assay and Determination of the Inhibition Constants. from Article 10.1016/j.bmcl.2004.08.034: “SAR and factor IXa crystal structure of a dual inhibitor of factors IXa and Xa.”	ki	0.0055	uM
2-chloro-N-[(2R)-2-(5,6-dimethyl-1H-benzimidazol-2-yl)-2-(3-fluorophenyl)ethyl]-4-(1,2,4-triazol-4-yl)benzamide	1252147: Inhibition of human coagulation factor 9a using fluorescent peptide CH3SO2-D-CHG-Gly-Arg-AFC-AcoH as substrate	ki	0.0057	uM
2-chloro-N-[(2S)-7-methyl-2-phenyl-3,4-dihydro-1H-pyrido[1,2-a]benzimidazol-2-yl]-4-(3-methyl-1,2,4-triazol-1-yl)benzamide	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0059	uM
2,6-dichloro-N-[(2R)-2-(6-chloro-4-methyl-1H-benzimidazol-2-yl)-2-(3-fluorophenyl)ethyl]-4-(3-methyl-1,2,4-triazol-1-yl)benzamide	1252147: Inhibition of human coagulation factor 9a using fluorescent peptide CH3SO2-D-CHG-Gly-Arg-AFC-AcoH as substrate	ki	0.0062	uM
2,6-dichloro-N-[(7S)-2,10-dimethyl-7-phenyl-8,9-dihydro-6H-pyrido[1,2-a]indol-7-yl]-4-(1,2,4-triazol-4-yl)benzamide	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0063	uM
1-(3-carbamimidoylphenyl)-N-[2-fluoro-4-[5-(trifluoromethyl)benzimidazol-1-yl]phenyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	1796940: Enzyme Assay and Determination of the Inhibition Constants. from Article 10.1016/j.bmcl.2004.08.034: “SAR and factor IXa crystal structure of a dual inhibitor of factors IXa and Xa.”	ki	0.0064	uM
2,6-dichloro-N-[(2R)-2-(3-fluorophenyl)-8-methyl-3,4-dihydro-1H-pyrido[1,2-b]indazol-2-yl]-4-(3-methyl-1,2,4-triazol-1-yl)benzamide	1252501: Inhibition of human F9a using CH3SO2-D-CHG-Gly-Arg-AFC.AcOH as substrate by fluorescence assay	ki	0.0066	uM

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
methyleugenol	decreases expression	1
bisphenol A	decreases expression	1
vitamin K1 oxide	increases activity, increases carboxylation, increases reduction	1
sodium arsenite	decreases expression	1
coumarin	increases response to substance	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
RB 006	affects binding, decreases activity, decreases reaction	1
RB 007	affects binding, decreases activity, decreases reaction	1
Acetaminophen	decreases expression	1
Betaine	increases secretion	1
Calcium Chloride	increases activity, affects cotreatment	1
Chenodeoxycholic Acid	decreases expression, affects cotreatment	1
Cholic Acids	affects cotreatment, affects expression	1
Contraceptives, Oral	increases expression	1
Deoxycholic Acid	affects cotreatment, decreases expression	1
Gentamicins	increases expression	1
Glycochenodeoxycholic Acid	affects cotreatment, decreases expression	1
Glycocholic Acid	affects cotreatment, decreases expression	1
Glycodeoxycholic Acid	decreases expression, affects cotreatment	1
Methyltestosterone	affects cotreatment, affects expression	1
N-Nitrosopyrrolidine	decreases expression	1
Vitamin K 1	increases activity, increases carboxylation, increases reduction	1
Tamoxifen	increases expression	1
Tartrazine	affects cotreatment, decreases expression	1
Valproic Acid	decreases expression	1
Warfarin	increases response to substance	1

ChEMBL screening assays

108 unique, capped per target: 107 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1005616	Binding	Inhibition of human factor 9a	Factor VIIa inhibitors: target hopping in the serine protease family using X-ray structure determination. — *Bioorg Med Chem Lett*
CHEMBL4621402	ADMET	Inhibition of human F9a using fluorescent peptide as substrate by florescence assay	Structure-Based Design and Preclinical Characterization of Selective and Orally Bioavailable Factor XIa Inhibitors: Demonstrating the Power of an Integrated S1 Protease Family Approach. — *J Med Chem*

Cellosaurus cell lines

7 cell lines: 4 cancer cell line, 2 transformed cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_AU00	293T-FIX	Transformed cell line	Female
CVCL_AU01	SK-HEP-1-FIX	Cancer cell line	Male
CVCL_B3RZ	SXMUi001-A	Induced pluripotent stem cell	Male
CVCL_B6DP	TMhep39	Cancer cell line
CVCL_B6DQ	TMhep48	Cancer cell line
CVCL_E4JT	CHO FIX.1F	Transformed cell line	Female
CVCL_XG90	HT-1080 JH-1/FIX	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 173 trials:

NCT	Phase	Status	Title
NCT00139828	Phase 4	COMPLETED	Post Marketing Study in Haemophilia B Patients Using Nonafact® (Human Coagulation Factor IX)
NCT00581126	Phase 4	COMPLETED	Study Evaluating BENEFIX in Previously Treated Patients With Hemophilia B
NCT00749476	Phase 4	COMPLETED	Study Evaluating BeneFIX in Patients With Haemophilia B, Previously Treated With Plasma Derived Factor IX
NCT01128881	Phase 4	COMPLETED	IMMUNINE Pre-Treatment Study
NCT01748201	Phase 4	COMPLETED	Viscosupplementation in Patients With Hemophilic Arthropathy
NCT02336178	Phase 4	COMPLETED	Safety and Efficacy of Benefix in Patients With Hemophilia B in Usual Care Settings in China
NCT03565237	Phase 4	COMPLETED	RIXUBIS PMS India (RIXUBIS PMS)
NCT04286412	Phase 4	COMPLETED	Nonacog Alfa Prophylaxis And Treatment Of Bleeding Episodes In Previously Treated Patients With Hemophilia B
NCT05856266	Phase 4	TERMINATED	An 18-month Low-interventional Study to Assess Joint Health in Haemophilia A and B Patients on Prophylaxis With Efmoroctocog Alfa or Eftrenonacog Alfa
NCT00037557	Phase 3	COMPLETED	Study Evaluating rFIX; BeneFIX in Severe Hemophilia B
NCT00093171	Phase 3	COMPLETED	Study Evaluating rFIX; BeneFIX® in Hemophilia B
NCT00093210	Phase 3	COMPLETED	Study Evaluating of Recombinant Human Factor IX (BeneFIX) and a New Formulation of BeneFIX (rFIX-R) in Moderate to Severe Hemophilia B
NCT00364182	Phase 3	COMPLETED	Study Comparing On-Demand Treatment With Two Prophylaxis Regimens Of BeneFIX In Patients With Severe Hemophilia B
NCT00851721	Phase 3	COMPLETED	Efficacy and Safety Study of Prophylactic Versus On-Demand Treatment With Feiba NF in Subjects With Hemophilia A or B and a High Titer Inhibitor
NCT00866606	Phase 3	COMPLETED	Study Evaluating On-Demand Treatment With BeneFIX In Chinese Subjects
NCT01174446	Phase 3	COMPLETED	Pivotal Study (Pharmacokinetics, Efficacy, Safety) of BAX 326 (rFIX) in Hemophilia B Patients
NCT01271868	Phase 3	TERMINATED	Study of Recombinant Factor IX Product, IB1001, in Previously Treated Pediatric Subjects With Hemophilia B
NCT01286779	Phase 3	COMPLETED	BAX 326 (rFIX) Continuation Study
NCT01335061	Phase 3	COMPLETED	Study To Compare On-Demand Treatment To A Prophylaxis Regimen Of BeneFIX In Subjects With Moderately Severe to Severe Hemophilia B
NCT01440946	Phase 3	COMPLETED	Study of Recombinant Coagulation Factor IX Fc Fusion Protein, BIIB029, in Previously Treated Pediatric Participants With Hemophilia B
NCT01507896	Phase 3	COMPLETED	BAX 326 Surgery Study in Hemophilia B Patients
NCT01662531	Phase 3	COMPLETED	A Safety, Efficacy and Pharmacokinetics Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Children With Hemophilia B
NCT01757405	Phase 3	COMPLETED	Recombinant Factor VIIa BI (rFVIIa BI) Treatment of Acute Bleeding Episodes Per an On-demand Regimen
NCT02048111	Phase 3	WITHDRAWN	Study of Recombinant Factor IX Product, IB1001, in Previously Treated Subjects With Hemophilia B
NCT02053792	Phase 3	COMPLETED	A Safety and Efficacy Extension Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Patients With Hemophilia B
NCT02234310	Phase 3	COMPLETED	Study to Determine the Safety and Efficacy of rFIXFc in Previously Untreated Males With Severe Hemophilia B
NCT03417102	Phase 3	COMPLETED	A Study of Fitusiran (ALN-AT3SC) in Severe Hemophilia A and B Patients With Inhibitors
NCT03417245	Phase 3	COMPLETED	A Study of Fitusiran (ALN-AT3SC) in Severe Hemophilia A and B Patients Without Inhibitors
NCT03569891	Phase 3	COMPLETED	HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients
NCT03587116	Phase 3	COMPLETED	A Study to Evaluate Prospective Efficacy and Safety Data of Current FIX Prophylaxis Replacement Therapy in Adult Hemophilia B Subjects (FIX:C≤2%) or Current FVIII Prophylaxis Replacement Therapy in Adult Hemophilia A Subjects (FVIII:C≤1%)
NCT03855280	Phase 3	COMPLETED	Evaluation of a Recombinant Factor IX Product, APVO101, in Previously-Treated Pediatric Patients With Hemophilia B
NCT03861273	Phase 3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
NCT03938792	Phase 3	COMPLETED	Study of the Efficacy and Safety PF-06741086 in Adult and Teenage Participants With Severe Hemophilia A or Moderately Severe to Severe Hemophilia B
NCT05145127	Phase 3	RECRUITING	Open-Label Extension Study of Marstacimab in Hemophilia Participants With or Without Inhibitors
NCT05487976	Phase 3	UNKNOWN	Clinical Study of Recombinant Human Activated Coagulation Factor VII for Injection in Patients With Hemophilia With Inhibitor
NCT05568719	Phase 3	RECRUITING	Safety and Effectiveness of Giroctocogene Fitelparvovec or Fidanacogene Elaparvovec in Patients With Hemophilia A or B Respectively
NCT05611801	Phase 3	RECRUITING	A Clinical Trial of Study Medicine (Marstacimab) in Pediatric Patients With Hemophilia A or Hemophilia B
NCT06003387	Phase 3	RECRUITING	Efficacy and Safety of CSL222 (Etranacogene Dezaparvovec) Gene Therapy in Adults With Hemophilia B With Pretreatment Adeno-associated Virus Serotype 5 (AAV5) Neutralizing Antibodies (Nabs)
NCT06399289	Phase 3	COMPLETED	Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Chinese Subjects With Hemophilia B Previously Treated With FIX Therapy
NCT06568302	Phase 3	TERMINATED	The Long-term Safety and Efficacy of SerpinPC in Subjects with Hemophilia Who Completed a Sponsored SerpinPC Clinical Trial
NCT06700096	Phase 3	RECRUITING	An Open-Label, Comparative Study of the Efficacy, Safety and Pharmacodynamics of Single Dose of ANB-002 in Patients With Hemophilia B
NCT07080905	Phase 3	RECRUITING	Phase 3, Open-label, Single-dose Study of CSL222 in Adolescent Male Subjects (≥ 12 to < 18 Years of Age) With Severe or Moderately Severe Hemophilia B
NCT01027364	Phase 3	COMPLETED	Study of Recombinant Factor IX Fc Fusion Protein (rFIXFc) in Participants With Hemophilia B
NCT01425723	Phase 3	COMPLETED	Long-Term Safety and Efficacy of rFIXFc in the Prevention and Treatment of Bleeding Episodes in Previously Treated Participants With Hemophilia B
NCT00947193	Phase 2	TERMINATED	Study of Ataluren (PTC124) in Hemophilia A and B
NCT02484092	Phase 2	COMPLETED	A Gene Therapy Study for Hemophilia B
NCT03091751	Phase 2	COMPLETED	Efficacy and Safety of AlphaNine Versus BeneFIX in Patients With Severe Hereditary Haemophilia B
NCT03307980	Phase 2	COMPLETED	Long-term Safety and Efficacy Study and Dose-Escalation Substudy of PF 06838435 in Individuals With Hemophilia B
NCT03489291	Phase 2	COMPLETED	Dose Confirmation Trial of AAV5-hFIXco-Padua
NCT03995784	Phase 2	COMPLETED	Study of Next-Generation Recombinant Factor IX Variant in Adult Subjects With Hemophilia B
NCT05789524	Phase 2	TERMINATED	The Efficacy and Safety of SerpinPC in Participants with Severe Hemophilia a or Moderately Severe to Severe Hemophilia B
NCT05789537	Phase 2	TERMINATED	A Study of SerpinPC in Participants with Hemophilia B (HemB) with Inhibitors
NCT00716716	Phase 1	COMPLETED	Phase I/IIa Study of FIXFc in Hemophilia B Patients
NCT00979238	Phase 1	COMPLETED	Dose-Escalation Study Of A Self Complementary Adeno-Associated Viral Vector For Gene Transfer in Hemophilia B
NCT01233440	Phase 1	COMPLETED	Safety and Pharmacokinetic Study of a Recombinant Coagulation Factor IX Albumin Fusion Protein in Subjects With Hemophilia B
NCT01620801	Phase 1	TERMINATED	Hemophilia B Gene Therapy With AAV8 Vector
NCT01921855	Phase 1	COMPLETED	Study of FVIIa Variant BAY86-6150 (B0189) in Subjects With Moderate or Severe Hemophilia Types A or B With or Without Inhibitors
NCT02035605	Phase 1	COMPLETED	A Phase 1 Study of an Investigational Drug, ALN-AT3SC, in Healthy Volunteers and Hemophilia A or B Patients
NCT02213250	Phase 1	COMPLETED	An Open-Label, Single Dose Pharmacokinetic Study of Benefix (Recombinant Factor IX) in Male Chinese Subjects With Hemophilia B
NCT02418793	Phase 1	COMPLETED	A Study of a Long-Acting r-Factor 7a (Factor VIIa) in Adult Men With Hemophilia A or B

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for F9 across ~30M SureChEMBL compounds — explore on Sugi Predict.