Venous thromboembolism

Summary

Venous thromboembolism (MONDO:0005399) is a disease with 75 cohort genes (1,043 GWAS associations across 64 studies) and 549 clinical trials. The dominant Reactome pathway is Defective F8 cleavage by thrombin (3 cohort genes). Top therapeutic interventions include enoxaparin sodium, fondaparinux, and dabigatran etexilate.

At a glance

• Cohort genes: 75
• GWAS associations: 1,043
• ClinVar variants: 10
• Clinical trials: 549

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	venous thromboembolism
Mondo ID	MONDO:0005399
EFO	EFO:0004286
MeSH	D054556
ICD-11	1197943614
NCIT	C99537
UMLS	C1861172
MedGen	348285
Is cancer (heuristic)	no

Also known as: venous thromboembolism

Data availability: 10 ClinVar variants · 1,043 GWAS associations (64 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › venous thromboembolism

Related subtypes (59): arterial disorder, ischemic colitis, thrombotic disease, capillary disorder, angiodysplasia, hepatic vascular disorder, vascular hemostatic disease, vein disorder, ischemic disease, peripheral vascular disease, ocular vascular disorder, cholesterol embolism, thoracic outlet syndrome, idiopathic spontaneous coronary artery dissection, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, angioosteohypertrophic syndrome, Bannayan-Riley-Ruvalcaba syndrome, arterial tortuosity syndrome, hereditary arterial and articular multiple calcification syndrome, pulmonary venoocclusive disease, multiple cutaneous and mucosal venous malformations, arterial dissection-lentiginosis syndrome, patent ductus arteriosus, multisystemic smooth muscle dysfunction syndrome, STING-associated vasculopathy with onset in infancy, capillary malformation, Ehlers-Danlos syndrome, vascular-like type, calciphylaxis, neonatal Marfan syndrome, Ehlers-Danlos syndrome, vascular type, lethal arteriopathy syndrome due to fibulin-4 deficiency, congenital portosystemic shunt, arterial calcification of infancy, vasculitis, Loeys-Dietz syndrome, skin vascular disease, lymphatic malformation, familial thoracic aortic aneurysm and aortic dissection, congenital anomaly of superior vena cava, congenital anomaly of the inferior vena cava, congenital anomaly of hepatic vein, congenital renal artery stenosis, internal carotid agenesis, coronary sinus stenosis, coronary sinus atresia, vascular occlusion disorder, vascular insufficiency disorder, blood vessel neoplasm, vascular ectasia, vascular disorder of penis, fibrocartilaginous embolism, vascular malformation, lymphatic vessel neoplasm, neurovascular disorder, superior vena cava syndrome, coronary microvascular disorder, segmental arterial mediolysis, bleeding disorder, vascular-type, arterial tortuosity-bone fragility syndrome

Genetics & variants

GWAS landscape

1,043 GWAS associations across 64 studies. Top hits map to 26 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1046205	5e-324	MCF2L	?
rs2073826	5e-324	ABO	?
rs10901252	5e-324	ABO	?
rs710446	6e-304	HRG-AS1, KNG1	?
rs6025	1e-300	F5	T	2.53
rs2066864	2e-284	FGG	A	0.21
rs3756011	4e-256	F11	A	0.19
rs9411377	1e-224	ABO	A	1.36
rs920065566	3e-194	ABO	T	0.28
rs2227402	4e-191	FGB	?
rs2769071	1e-180	ABO	?
rs1799963	1e-175	F2	A	0.68
rs687289	5e-175	ABO	?
rs2519093	4e-169	ABO	T	1.4
rs2040445	4e-168	NME7, ATP1B1	?	0.81
rs1209731	2e-164	NME7	?	0.82
rs17490626	3e-160	TSPAN15	C	0.23
rs12644950	7e-159	FGG - LRAT	?	0.19
rs145163454	6e-146	ATP1B1	?	0.83
rs579459	4e-145	ABO - Y_RNA	C	1.36
rs8176704	5e-134	ABO	?	0.31
rs2420372	9e-122	F5	?
rs78707713	1e-111	TSPAN15	T	0.21
rs8176719	7e-106	ABO	?	1.31
rs6060288	2e-102	PROCR	A	0.12
rs1063856	3e-99	VWF	?
chr4:186285095	8e-99		A	0.19
rs4253417	8e-96	F11	C	1.22
rs2066865	2e-88	FGA - FGG	A	1.22
rs28446901	2e-87	ADAMTS13	?	0.28

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90451757	Gagnon E	2024	44,223	847,152	Genetic assessment of efficacy and safety profiles of coagulation cascade proteins identifies Factors II and XI as actionable anticoagulant targets.
GCST90129535	Temprano-Sagrera G	2022	30,234	172,122	Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations.
GCST90129536	Temprano-Sagrera G	2022	30,234	172,122	Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations.
GCST90129537	Temprano-Sagrera G	2022	30,234	172,122	Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations.
GCST90129538	Temprano-Sagrera G	2022	30,234	172,122	Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations.
GCST90129539	Temprano-Sagrera G	2022	30,234	172,122	Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations.
GCST90129540	Temprano-Sagrera G	2022	30,234	172,122	Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations.
GCST90129541	Temprano-Sagrera G	2022	30,234	172,122	Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations.
GCST009029	Lindstrom S	2019	29,435	157,769	Genomic and Transcriptomic Association Studies Identify 16 Novel Susceptibility Loci for Venous Thromboembolism.
GCST009030	Lindstrom S	2019	29,435	157,769	Genomic and Transcriptomic Association Studies Identify 16 Novel Susceptibility Loci for Venous Thromboembolism.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	5
Tier 2: splice/UTR	5
Tier 3: regulatory	0
Tier 4: intronic/intergenic	40

MAF distribution

Bucket	Variants
common (>=0.05)	47
low_freq (0.01-0.05)	2
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	30
intergenic_variant	8
3_prime_UTR_variant	5
missense_variant	4
frameshift_variant	1
unknown	1
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs687289	9	133261703	A>C,G,T	0.358	intron_variant	ABO		Tier 4: intronic/intergenic
rs6025	1	169549811	C>A,G,T	0.026	missense_variant	F5		Tier 1: coding
rs505922	9	133273813	C>T	0.367	intron_variant	ABO		Tier 4: intronic/intergenic
rs1046205	13	113097743	A>T	0.05	3_prime_UTR_variant	MCF2L	5e-324	Tier 2: splice/UTR
rs2073826	9	133261560	G>A,C,T	0.05	intron_variant	ABO	5e-324	Tier 4: intronic/intergenic
rs10901252	9	133252613	G>A,C,T	0.05	3_prime_UTR_variant	ABO	5e-324	Tier 2: splice/UTR
rs710446	3	186742138	T>A,C,G	0.05	missense_variant	HRG-AS1, KNG1	6e-304	Tier 1: coding
rs2066864	4	154604543	G>A,T	0.05	3_prime_UTR_variant	FGG	2e-284	Tier 2: splice/UTR
rs3756011	4	186285095	C>A,T	0.392	intron_variant	F11	4e-256	Tier 4: intronic/intergenic
rs9411377	9	133269992	A>C,G	0.313	intron_variant	ABO	1e-224	Tier 4: intronic/intergenic
rs920065566	9	133273813		0.368	intron_variant	ABO	3e-194	Tier 4: intronic/intergenic
rs2227402	4	154565318	T>A,G	0.05	intron_variant	FGB	4e-191	Tier 4: intronic/intergenic
rs2769071	9	133270565	G>A	0.05	intron_variant	ABO	1e-180	Tier 4: intronic/intergenic
rs1799963	11	46739505	G>A	0.014	3_prime_UTR_variant	F2	1e-175	Tier 2: splice/UTR
rs2519093	9	133266456	T>C	0.05	intron_variant	ABO	4e-169	Tier 4: intronic/intergenic
rs2040445	1	169247174	C>G,T	0.05	intron_variant	NME7, ATP1B1	4e-168	Tier 4: intronic/intergenic
rs1209731	1	169355555	T>A,C,G	0.05	intron_variant	NME7	2e-164	Tier 4: intronic/intergenic
rs17490626	10	69458890	G>A,C	0.05	intron_variant	TSPAN15	3e-160	Tier 4: intronic/intergenic
rs12644950	4	154616169	G>A,C	0.05	intergenic_variant	FGG - LRAT	7e-159	Tier 4: intronic/intergenic
rs145163454	1	169121510	T>A,C	0.05	intron_variant	ATP1B1	6e-146	Tier 4: intronic/intergenic
rs579459	9	133278724	C>T	0.05	intergenic_variant	ABO - Y_RNA	4e-145	Tier 4: intronic/intergenic
rs8176704	9	133260148	G>A,C	0.05	intron_variant	ABO	5e-134	Tier 4: intronic/intergenic
rs2420372	1	169528818	A>C,G,T	0.05	intron_variant	F5	9e-122	Tier 4: intronic/intergenic
rs78707713	10	69485520	T>A,C	0.12	intron_variant	TSPAN15	1e-111	Tier 4: intronic/intergenic
rs8176719	9	133257522	T>TC	0.05	frameshift_variant	ABO	7e-106	Tier 1: coding
rs6060288	20	35184440	G>A	0.05	intergenic_variant	PROCR	2e-102	Tier 4: intronic/intergenic
rs1063856	12	6044368	T>C,G	0.05	missense_variant	VWF	3e-99	Tier 1: coding
chr4:186285095				0.395			8e-99	Tier 4: intronic/intergenic
rs4253417	4	186277851	T>C,G	0.387	intron_variant	F11	8e-96	Tier 4: intronic/intergenic
rs2066865	4	154604124	G>A,C,T	0.246	intergenic_variant	FGA - FGG	2e-88	Tier 4: intronic/intergenic

ClinVar germline variants

10 retrieved; paginated sample, class counts are floors:

6 benign, 1 pathogenic/likely pathogenic/pathogenic, low penetrance/established risk allele; risk factor, 1 drug response, 1 association not found, 1 affects

ClinVar	Variant (HGVS)	Gene	Classification	Review
13310	NM_000506.5(F2):c.*97G>A	F2	Pathogenic/Likely pathogenic/Pathogenic, low penetrance/Established risk allele; risk factor	criteria provided, multiple submitters, no conflicts
2211	NM_024006.4(VKORC1):c.-1639G>A	VKORC1	drug response	reviewed by expert panel
3027423	NC_012920.1(MT-CYB):m.16223C>T		association not found	no assertion criteria provided
3066071	NC_012920.1(MT-CYB):m.73A>G		Affects	no assertion criteria provided
3027421	NC_012920.1(MT-CO3):m.9540T>C	MT-CO3	Benign	criteria provided, single submitter
140587	NC_012920.1(MT-CYB):m.14766C>T	MT-CYB	Benign	criteria provided, multiple submitters, no conflicts
3027422	NC_012920.1(MT-ND4):m.12007G>A	MT-ND4	Benign	no assertion criteria provided
3027424	NC_012920.1(MT-ND4):m.11719G>A	MT-ND4	Benign	criteria provided, single submitter
441148	NC_012920.1(MT-RNR1):m.750A>G	MT-RNR1	Benign	criteria provided, single submitter
140589	NC_012920.1(MT-CYB):m.15043G>A	MT-TT	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 45 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
F2	F2	GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
F2	Orphanet:325	Congenital factor II deficiency
F2	Orphanet:329217	Cerebral sinovenous thrombosis
SEMA3D	Orphanet:388	Hirschsprung disease
SLC19A2	Orphanet:49827	Thiamine-responsive megaloblastic anemia syndrome
BTNL2	Orphanet:797	Sarcoidosis
TCN2	Orphanet:859	Transcobalamin deficiency
THBD	Orphanet:436169	Thrombomodulin-related bleeding disorder
THBD	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
CEP41	Orphanet:220493	Joubert syndrome with ocular defect
CEP41	Orphanet:475	Isolated Joubert syndrome
VWF	Orphanet:166078	Von Willebrand disease type 1
VWF	Orphanet:166084	Von Willebrand disease type 2A
VWF	Orphanet:166087	Von Willebrand disease type 2B
VWF	Orphanet:166090	Von Willebrand disease type 2M
VWF	Orphanet:166093	Von Willebrand disease type 2N
VWF	Orphanet:166096	Von Willebrand disease type 3
WWOX	Orphanet:251510	46,XY partial gonadal dysgenesis
WWOX	Orphanet:284282	Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to WWOX deficiency
WWOX	Orphanet:708171	Facial dysmorphism-corpus callosum hypoplasia-infantile epileptic encephalopathy
WWOX	Orphanet:99977	Squamous cell carcinoma of the esophagus
GP6	Orphanet:98885	Bleeding diathesis due to glycoprotein VI deficiency
SRRM2	Orphanet:652487	Developmental delay-overweight-facial dysmorphism-behavioral abnormalities syndrome
ZFPM2	Orphanet:2140	Congenital diaphragmatic hernia
ZFPM2	Orphanet:251510	46,XY partial gonadal dysgenesis
ZFPM2	Orphanet:3303	Tetralogy of Fallot
TSPOAP1	Orphanet:101150	Autosomal recessive dopa-responsive dystonia
CDH11	Orphanet:1299	Branchioskeletogenital syndrome
RIC1	Orphanet:199306	Cleft lip/palate
ROBO4	Orphanet:402075	Familial bicuspid aortic valve
TRPM3	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
NUP205	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
CORIN	Orphanet:275555	Preeclampsia
GEMIN5	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability
NME7	Orphanet:101063	Situs inversus totalis
DPYSL5	Orphanet:528084	Non-specific syndromic intellectual disability
DPYSL5	Orphanet:7	3C syndrome
BCOR	Orphanet:2712	Oculofaciocardiodental syndrome
BCOR	Orphanet:457246	Clear cell sarcoma of kidney
BCOR	Orphanet:520	Acute promyelocytic leukemia
BCOR	Orphanet:568	Microphthalmia, Lenz type
ANTXR2	Orphanet:2028	Juvenile hyaline fibromatosis
ANTXR2	Orphanet:2176	Infantile systemic hyalinosis
CYP4V2	Orphanet:41751	Bietti crystalline dystrophy
VKORC1	Orphanet:98434	Hereditary combined deficiency of vitamin K-dependent clotting factors
BRCC3	Orphanet:280679	Moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome

Cohort genes → proteins

75 cohort genes, 74 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	73
gwas_and_clinvar	1
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
F2	HGNC:3535	ENSG00000180210	P00734	Prothrombin	gwas,clinvar
RIT2	HGNC:10017	ENSG00000152214	Q99578	GTP-binding protein Rit2	gwas
BCL7A	HGNC:1004	ENSG00000110987	Q4VC05	B-cell CLL/lymphoma 7 protein family member A	gwas
SEMA3D	HGNC:10726	ENSG00000153993	O95025	Semaphorin-3D	gwas
SLC10A2	HGNC:10906	ENSG00000125255	Q12908	Ileal sodium/bile acid cotransporter	gwas
SLC19A2	HGNC:10938	ENSG00000117479	O60779	Thiamine transporter 1	gwas
SNRNP70	HGNC:11150	ENSG00000104852	P08621	U1 small nuclear ribonucleoprotein 70 kDa	gwas
SPRY2	HGNC:11270	ENSG00000136158	O43597	Protein sprouty homolog 2	gwas
BTNL2	HGNC:1142	ENSG00000204290	Q9UIR0	Butyrophilin-like protein 2	gwas
STX10	HGNC:11428	ENSG00000104915	O60499	Syntaxin-10	gwas
TCN2	HGNC:11653	ENSG00000185339	P20062	Transcobalamin-2	gwas
TGM4	HGNC:11780	ENSG00000163810	P49221	Protein-glutamine gamma-glutamyltransferase 4	gwas
THBD	HGNC:11784	ENSG00000178726	P07204	Thrombomodulin	gwas
TNFSF13B	HGNC:11929	ENSG00000102524	Q9Y275	Tumor necrosis factor ligand superfamily member 13B	gwas
CEP41	HGNC:12370	ENSG00000106477	Q9BYV8	Centrosomal protein of 41 kDa	gwas
LCA5L	HGNC:1255	ENSG00000157578	O95447	Lebercilin-like protein	gwas
VWF	HGNC:12726	ENSG00000110799	P04275	von Willebrand factor	gwas
WWOX	HGNC:12799	ENSG00000186153	Q9NZC7	WW domain-containing oxidoreductase	gwas
ZNF160	HGNC:12948	ENSG00000170949	Q9HCG1	Zinc finger protein 160	gwas
ZNF71	HGNC:13141	ENSG00000197951	Q9NQZ8	Endothelial zinc finger protein induced by tumor necrosis factor alpha	gwas
C4BPA	HGNC:1325	ENSG00000123838	P04003	C4b-binding protein alpha chain	gwas
FBXL7	HGNC:13604	ENSG00000183580	Q9UJT9	F-box/LRR-repeat protein 7	gwas
GP6	HGNC:14388	ENSG00000088053	Q9HCN6	Platelet glycoprotein VI	gwas
PARD3B	HGNC:14446	ENSG00000116117	Q8TEW8	Partitioning defective 3 homolog B	gwas
MTPN	HGNC:15667	ENSG00000105887	P58546	Myotrophin	gwas
CD93	HGNC:15855	ENSG00000125810	Q9NPY3	Complement component C1q receptor	gwas
EDEM2	HGNC:15877	ENSG00000088298	Q9BV94	ER degradation-enhancing alpha-mannosidase-like protein 2	gwas
ZFP64	HGNC:15940	ENSG00000020256	Q9NTW7	Zinc finger protein 64	gwas
SRRM2	HGNC:16639	ENSG00000167978	Q9UQ35	Serine/arginine repetitive matrix protein 2	gwas
ZFPM2	HGNC:16700	ENSG00000169946	Q8WW38	Zinc finger protein ZFPM2	gwas
CD48	HGNC:1683	ENSG00000117091	P09326	CD48 antigen	gwas
TSPOAP1	HGNC:16831	ENSG00000005379	O95153	Peripheral-type benzodiazepine receptor-associated protein 1	gwas
LY86	HGNC:16837	ENSG00000112799	O95711	Lymphocyte antigen 86	gwas
CTNNBIP1	HGNC:16913	ENSG00000178585	Q9NSA3	Beta-catenin-interacting protein 1	gwas
SLC44A2	HGNC:17292	ENSG00000129353	Q8IWA5	Choline transporter-like protein 2	gwas
CDH11	HGNC:1750	ENSG00000140937	P55287	Cadherin-11	gwas
RIC1	HGNC:17686	ENSG00000107036	Q4ADV7	Guanine nucleotide exchange factor subunit RIC1	gwas
SMG6	HGNC:17809	ENSG00000070366	Q86US8	Telomerase-binding protein EST1A	gwas
ROBO4	HGNC:17985	ENSG00000154133	Q8WZ75	Roundabout homolog 4	gwas
TRPM3	HGNC:17992	ENSG00000083067	Q9HCF6	Transient receptor potential cation channel subfamily M member 3	gwas
KHDRBS3	HGNC:18117	ENSG00000131773	O75525	KH domain-containing, RNA-binding, signal transduction-associated protein 3	gwas
KCNG3	HGNC:18306	ENSG00000171126	Q8TAE7	Voltage-gated potassium channel regulatory subunit KCNG3	gwas
ADGRL2	HGNC:18582	ENSG00000117114	O95490	Adhesion G protein-coupled receptor L2	gwas
RGSL1	HGNC:18636	ENSG00000121446	A5PLK6	Regulator of G-protein signaling protein-like	gwas
NUP205	HGNC:18658	ENSG00000155561	Q92621	Nuclear pore complex protein Nup205	gwas
RIN3	HGNC:18751	ENSG00000100599	Q8TB24	Ras and Rab interactor 3	gwas
POLE4	HGNC:18755	ENSG00000115350	Q9NR33	DNA polymerase epsilon subunit 4	gwas
CORIN	HGNC:19012	ENSG00000145244	Q9Y5Q5	Atrial natriuretic peptide-converting enzyme	gwas
TBC1D4	HGNC:19165	ENSG00000136111	O60343	TBC1 domain family member 4	gwas
CMTM7	HGNC:19178	ENSG00000153551	Q96FZ5	CKLF-like MARVEL transmembrane domain-containing protein 7	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
F2	Prothrombin	Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C.
RIT2	GTP-binding protein Rit2	Binds and exchanges GTP and GDP.
SEMA3D	Semaphorin-3D	Induces the collapse and paralysis of neuronal growth cones.
SLC10A2	Ileal sodium/bile acid cotransporter	Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine.
SLC19A2	Thiamine transporter 1	High-affinity transporter for the intake of thiamine.
SNRNP70	U1 small nuclear ribonucleoprotein 70 kDa	Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5’ splice-site and the subsequent assembly of the spliceosome.
SPRY2	Protein sprouty homolog 2	Antagonist of fibroblast growth factor (FGF) pathways via inhibition of FGF-mediated phosphorylation of ERK1/2.
BTNL2	Butyrophilin-like protein 2	Negative regulator of T-cell proliferation.
STX10	Syntaxin-10	SNARE involved in vesicular transport from the late endosomes to the trans-Golgi network.
TCN2	Transcobalamin-2	Primary vitamin B12-binding and transport protein.
TGM4	Protein-glutamine gamma-glutamyltransferase 4	Associated with the mammalian reproductive process.
THBD	Thrombomodulin	Endothelial cell receptor that plays a critical role in regulating several physiological processes including hemostasis, coagulation, fibrinolysis, inflammation, and angiogenesis.
TNFSF13B	Tumor necrosis factor ligand superfamily member 13B	Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA.
CEP41	Centrosomal protein of 41 kDa	Required during ciliogenesis for tubulin glutamylation in cilium.
VWF	von Willebrand factor	Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface receptor complex GPIb-IX-V.
WWOX	WW domain-containing oxidoreductase	Putative oxidoreductase.
ZNF160	Zinc finger protein 160	May be involved in transcriptional regulation.
ZNF71	Endothelial zinc finger protein induced by tumor necrosis factor alpha	May be involved in transcriptional regulation.
C4BPA	C4b-binding protein alpha chain	Controls the classical pathway of complement activation.
FBXL7	F-box/LRR-repeat protein 7	Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex.
GP6	Platelet glycoprotein VI	Collagen receptor involved in collagen-induced platelet adhesion and activation.
PARD3B	Partitioning defective 3 homolog B	Putative adapter protein involved in asymmetrical cell division and cell polarization processes.
MTPN	Myotrophin	Promotes dimerization of NF-kappa-B subunits and regulates NF-kappa-B transcription factor activity.
CD93	Complement component C1q receptor	Cell surface receptor that plays a role in various physiological processes including inflammation, phagocytosis, and cell adhesion.
EDEM2	ER degradation-enhancing alpha-mannosidase-like protein 2	Involved in the endoplasmic reticulum-associated degradation (ERAD) pathway that targets misfolded glycoproteins for degradation in an N-glycan-dependent manner.
ZFP64	Zinc finger protein 64	May be involved in the regulation of mesenchymal cell differentiation through transactivation of NOTCH1 target genes.
SRRM2	Serine/arginine repetitive matrix protein 2	Required for pre-mRNA splicing as component of the spliceosome.
ZFPM2	Zinc finger protein ZFPM2	Transcription regulator that plays a central role in heart morphogenesis and development of coronary vessels from epicardium, by regulating genes that are essential during cardiogenesis.
CD48	CD48 antigen	Glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein that interacts via its N-terminal immunoglobulin domain with cell surface receptors including CD244/2B4 or CD2 to regulate immune cell function and activation.
TSPOAP1	Peripheral-type benzodiazepine receptor-associated protein 1	Required for synaptic transmission regulation.
LY86	Lymphocyte antigen 86	May cooperate with CD180 and TLR4 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) and cytokine production.
CTNNBIP1	Beta-catenin-interacting protein 1	Prevents the interaction between CTNNB1 and TCF family members, and acts as a negative regulator of the Wnt signaling pathway.
SLC44A2	Choline transporter-like protein 2	Choline/H+ antiporter, mainly in mitochondria.
CDH11	Cadherin-11	Cadherins are calcium-dependent cell adhesion proteins.
RIC1	Guanine nucleotide exchange factor subunit RIC1	The RIC1-RGP1 complex acts as a guanine nucleotide exchange factor (GEF), which activates RAB6A by exchanging bound GDP for free GTP, and may thereby be required for efficient fusion of endosome-derived vesicles with the Golgi compartment.
SMG6	Telomerase-binding protein EST1A	Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini.
ROBO4	Roundabout homolog 4	Receptor for Slit proteins, at least for SLIT2, and seems to be involved in angiogenesis and vascular patterning.
TRPM3	Transient receptor potential cation channel subfamily M member 3	Constitutively active, non-selective divalent cation-conducting channel that is permeable to Ca(2+), Mn(2+), and Mg(2+), with a high permeability for Ca(2+).
KHDRBS3	KH domain-containing, RNA-binding, signal transduction-associated protein 3	RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion.
KCNG3	Voltage-gated potassium channel regulatory subunit KCNG3	Regulatory subunit of the voltage-gated potassium (Kv) channel which, when coassembled with KCNB1, modulates the kinetics parameters of the heterotetrameric channel namely the inactivation and deactivation rate.
ADGRL2	Adhesion G protein-coupled receptor L2	Orphan adhesion G-protein coupled receptor (aGPCR), which mediates synapse specificity.
NUP205	Nuclear pore complex protein Nup205	Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance.
RIN3	Ras and Rab interactor 3	Ras effector protein that functions as a guanine nucleotide exchange (GEF) for RAB5B and RAB31, by exchanging bound GDP for free GTP.
POLE4	DNA polymerase epsilon subunit 4	Accessory component of the DNA polymerase epsilon complex.
CORIN	Atrial natriuretic peptide-converting enzyme	Serine-type endopeptidase involved in atrial natriuretic peptide (NPPA) and brain natriuretic peptide (NPPB) processing.
TBC1D4	TBC1 domain family member 4	May act as a GTPase-activating protein for RAB2A, RAB8A, RAB10 and RAB14.
ST6GALNAC3	Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 3	Transfers the sialyl group (N-acetyl-alpha-neuraminyl or NeuAc) from CMP-NeuAc to the GalNAc residue on the NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc sequence of glycoproteins and glycolipids forming an alpha-2,6-linkage.
STXBP5	Syntaxin-binding protein 5	Plays a regulatory role in calcium-dependent exocytosis and neurotransmitter release.
GEMIN5	Gem-associated protein 5	The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs.
NME7	Nucleoside diphosphate kinase 7	Possesses an intrinsic kinase activity.

Protein-family classification

Druggable: 26 · Difficult: 13 · Unknown: 36 · Druggable fraction: 0.35

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	10	3.9×	0.003
Protease	5	2.4×	0.248
Scaffold/PPI	8	1.8×	0.248
Ion channel	2	3.0×	0.400
Complement	1	3.6×	0.539
Transporter	1	1.0×	0.960
Other/Unknown	36	0.9×	0.960
Enzyme (other)	5	0.8×	0.960
Transcription factor	5	0.6×	0.960
Kinase	1	0.4×	0.960
GPCR	1	0.3×	0.960

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
F2	Protease	yes	3.4.21.5	Kringle, GLA_domain, Trypsin_dom
RIT2	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
BCL7A	Other/Unknown	no		BCL7
SEMA3D	Antibody/Immunoglobulin	yes		Semap_dom, Ig_sub, Ig-like_dom
SLC10A2	Other/Unknown	no		BilAc:Na_symport/Acr3, Bilac:Na_transpt, Na+/solute_symporter_sf
SLC19A2	Transporter	yes		Folate_carrier, ThTr-1, MFS_trans_sf
SNRNP70	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, U1snRNP70_N
SPRY2	Other/Unknown	no		Sprouty, Sprouty_domain
BTNL2	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig_sub, Ig-like_dom
STX10	Other/Unknown	no		T_SNARE_dom, Syntaxin/epimorphin_CS, SNARE
TCN2	Other/Unknown	no		Cbl-bd_prot, Terpenoid_cyclase/PrenylTrfase, Cobalamin_Transport
TGM4	Antibody/Immunoglobulin	yes	2.3.2.13	Transglutaminase_N, Transglutaminase-like, Transglutaminase_C
THBD	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, C-type_lectin-like
TNFSF13B	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNF_Ligand_Superfamily
CEP41	Other/Unknown	no		Rhodanese-like_dom, Rhodanese-like_dom_sf, CEP41
LCA5L	Other/Unknown	no		Lebercilin-like, Lebercilin_dom
VWF	Other/Unknown	no		VWF_dom, VWF_type-D, VWF_A
WWOX	Scaffold/PPI	no		WW_dom, SDR_fam, WW_dom_sf
ZNF160	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
ZNF71	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, C2H2-ZF_domain
C4BPA	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, C4bp_oligo
FBXL7	Other/Unknown	no		F-box_dom, Leu-rich_rpt_Cys-con_subtyp, LRR_dom_sf
GP6	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_fold
PARD3B	Scaffold/PPI	no		PDZ, Par3/HAL_N, PDZ_sf
MTPN	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf
CD93	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, C-type_lectin-like
EDEM2	Other/Unknown	no		Glyco_hydro_47, 6hp_glycosidase-like_sf, Seven-hairpin_glycosidases
ZFP64	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, C2H2-ZF_domain-containing
SRRM2	Other/Unknown	no		mRNA_splic_Cwf21_dom, Spt5_C_dom, SRRM2_cwf21
ZFPM2	Transcription factor	no		Znf_C2H2_type, Znf_CCHC_FOG, Znf_C2H2_sf
CD48	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
TSPOAP1	Antibody/Immunoglobulin	yes		SH3_domain, FN3_dom, Ig-like_fold
LY86	Other/Unknown	no		ML_dom, Ig_E-set, LY86
CTNNBIP1	Other/Unknown	no		ICAT_dom, ICAT_sf
SLC44A2	Other/Unknown	no		Choline_transptr-like
CDH11	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf
RIC1	Scaffold/PPI	no		RIC1_C, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
SMG6	Other/Unknown	no		PIN_dom, TPR-like_helical_dom_sf, DNA/RNA-bd_Est1-type
ROBO4	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
TRPM3	Ion channel	yes		Ion_trans_dom, TRPM_tetra, TRPM_tetra_sf
KHDRBS3	Other/Unknown	no		KH_dom, Sam68-YY, Qua1_dom
KCNG3	Ion channel	yes		BTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv
ADGRL2	GPCR	yes		GPS, GPCR_2_secretin-like, Lectin_gal-bd_dom
RGSL1	Other/Unknown	no		RGS, RGS_sf, RGS_subdomain_2
NUP205	Other/Unknown	no		Nup186/Nup192/Nup205
RIN3	Scaffold/PPI	no		RA_dom, SH2, VPS9
POLE4	Enzyme (other)	yes	2.7.7.7	CBFA_NFYB_domain, Histone-fold, Transcr_DNA_Rep_Reg
CORIN	Protease	yes		SRCR, Trypsin_dom, LDrepeatLR_classA_rpt
TBC1D4	Other/Unknown	no		Rab-GAP-TBC_dom, PTB/PI_dom, PH-like_dom_sf
CMTM7	Other/Unknown	no		Marvel, MARVEL-CKLF_proteins

Expression context

Cohort genes with no expression data: 1.

65 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	74
unknown	1

Top tissues across cohort

Tissue	Cohort genes
monocyte	8
cortical plate	6
ventricular zone	6
granulocyte	6
leukocyte	6
male germ line stem cell (sensu Vertebrata) in testis	5
ganglionic eminence	5
primordial germ cell in gonad	5
right testis	5
secondary oocyte	4
sperm	4
endothelial cell	4
adrenal tissue	4
liver	3
right lobe of liver	3
cerebellar cortex	3
cerebellar hemisphere	3
buccal mucosa cell	3
ileal mucosa	3
oocyte	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
F2	117	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
RIT2	128	tissue_specific	marker	cerebellar cortex, cerebellar hemisphere, cerebellum
BCL7A	137	ubiquitous	marker	cortical plate, ganglionic eminence, embryo
SEMA3D	183	ubiquitous	marker	buccal mucosa cell, tendon of biceps brachii, spleen
SLC10A2	49	tissue_specific	marker	ileal mucosa, jejunal mucosa, duodenum
SLC19A2	282	ubiquitous	marker	secondary oocyte, oocyte, gastrocnemius
SNRNP70	297	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
SPRY2	281	ubiquitous	marker	cartilage tissue, tibial nerve, right hemisphere of cerebellum
BTNL2	106		yes	sural nerve, ventricular zone, primordial germ cell in gonad
STX10	282	ubiquitous	marker	monocyte, granulocyte, mononuclear cell
TCN2	198	ubiquitous	marker	gall bladder, metanephros cortex, right lung
TGM4	100	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, prostate gland, bone marrow
THBD	259	ubiquitous	marker	gingival epithelium, gingiva, vena cava
TNFSF13B	226	broad	marker	monocyte, leukocyte, blood
CEP41	237	ubiquitous	marker	sperm, left testis, right testis
LCA5L	175	broad	marker	left testis, right testis, sperm
VWF	289	broad	marker	urethra, tendon of biceps brachii, apex of heart
WWOX	286	ubiquitous	marker	parotid gland, cervix squamous epithelium, cranial nerve II
ZNF160	294	ubiquitous	marker	renal medulla, endothelial cell, pylorus
ZNF71	179	ubiquitous	yes	primordial germ cell in gonad, ganglionic eminence, cortical plate
C4BPA	166	tissue_specific	marker	right lobe of liver, liver, lower lobe of lung
FBXL7	277	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
GP6	126	tissue_specific	yes	monocyte, leukocyte, male germ line stem cell (sensu Vertebrata) in testis
PARD3B	200	ubiquitous	marker	sural nerve, cardiac muscle of right atrium, ventricular zone
MTPN	256	ubiquitous	marker	cardiac muscle of right atrium, upper arm skin, ileal mucosa
CD93	272	broad	marker	visceral pleura, lower lobe of lung, pleura
EDEM2	241	ubiquitous	marker	granulocyte, monocyte, leukocyte
ZFP64	288	ubiquitous	yes	germinal epithelium of ovary, gingival epithelium, secondary oocyte
SRRM2	301	ubiquitous	marker	right uterine tube, right hemisphere of cerebellum, right lobe of thyroid gland
ZFPM2	239	ubiquitous	marker	skeletal muscle tissue of biceps brachii, germinal epithelium of ovary, biceps brachii

Protein interactions among cohort

Intra-cohort edges: 16.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NME7	6,011
WWOX	5,892
SNRNP70	5,539
VWF	5,204
SRRM2	3,507
BRCC3	3,428
RIT2	3,234
TNFSF13B	3,234
CD48	3,153
NUP205	2,881

Intra-cohort edges

A	B	Sources
ADGRL2	CNTN6	string_interaction
ADTRP	CMTM7	biogrid_interaction, intact
ANTXR2	DPYSL5	biogrid_interaction
ANTXR2	VWF	string_interaction
CD93	ROBO4	string_interaction
F2	THBD	biogrid_interaction, intact, string_interaction
F2	VKORC1	string_interaction
F2	VWF	string_interaction
GEMIN5	SNRNP70	biogrid_interaction, intact
GP6	TSPAN15	string_interaction
GP6	VWF	string_interaction
RIN3	ZNF71	intact
SCD5	SLC19A2	intact
SLC44A2	TSPAN15	string_interaction
SLC44A2	VWF	string_interaction
THBD	VWF	string_interaction

Structural data

PDB: 40 · AlphaFold-only: 34 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
F2	P00734	475
VWF	P04275	48
SRRM2	Q9UQ35	25
GEMIN5	Q8TEQ6	16
ANTXR2	P58335	14
THBD	P07204	13
TNFSF13B	Q9Y275	12
SNRNP70	P08621	11
TCN2	P20062	11
C4BPA	P04003	9
BCL7A	Q4VC05	6
GP6	Q9HCN6	6
VKORC1	Q9BQB6	6
SPRY2	O43597	5
SMG6	Q86US8	5
KHDRBS3	O75525	5
NUP205	Q92621	5
BCOR	Q6W2J9	5
NLRP2	Q9NX02	5
MTPN	P58546	4
BRCC3	P46736	4
CTNNBIP1	Q9NSA3	3
DPYSL5	Q9BPU6	3
TSPAN15	O95858	3
SLC19A2	O60779	2
CD93	Q9NPY3	2
ZFP64	Q9NTW7	2
RIN3	Q8TB24	2
TBC1D4	O60343	2
NME7	Q9Y5B8	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TGM4	P49221	92.09
CYP4V2	Q6ZWL3	91.05
ADTRP	Q96IZ2	90.99
SCD5	Q86SK9	89.99
ST6GALNAC3	Q8NDV1	89.19
RIT2	Q99578	88.46
CNTN6	Q9UQ52	86.19
BTNL2	Q9UIR0	85.97
EDEM2	Q9BV94	85.61
CATSPERB	Q9H7T0	84.99
SEMA3D	O95025	84.10
SLC44A2	Q8IWA5	83.62
SLC10A2	Q12908	82.88
POLE4	Q9NR33	82.79
FBXL7	Q9UJT9	82.67
KCNG3	Q8TAE7	80.07
COX7A2L	O14548	79.89
STXBP5	Q5T5C0	78.93
CDH11	P55287	77.65
ZNF71	Q9NQZ8	77.36
RIC1	Q4ADV7	73.43
CEP41	Q9BYV8	71.06
CMTM7	Q96FZ5	70.28
CORIN	Q9Y5Q5	70.20
ZNF160	Q9HCG1	68.98
RGSL1	A5PLK6	67.79
FRMD1	Q8N878	66.72
LCA5L	O95447	62.76
TSPOAP1	O95153	57.91
ROBO4	Q8WZ75	57.67

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 548. Enrichment computed across 182 evidence-associated genes (116 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 116 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective F8 cleavage by thrombin	3	98.5×	2e-04	F2, VWF, F8
Amplification and propagation of coagulation cascade	5	27.4×	2e-04	F2, VWF, F5, F8, F9
Regulation of clotting cascade	7	14.1×	2e-04	F2, THBD, VWF, F5, F8, F9, PROCR
Initiation of coagulation cascade	5	20.5×	5e-04	F2, VWF, F5, F8, F9
R-HSA-140837	3	36.9×	0.006	F2, KLKB1, KNG1
Defective F8 binding to von Willebrand factor	2	98.5×	0.009	VWF, F8
FXIIa, PKa-dependent activation of coagulation pathway	3	29.5×	0.009	F9, KLKB1, KNG1
R-HSA-9651496	2	65.6×	0.012	F2, KLKB1
Defective factor IX causes thrombophilia	2	65.6×	0.012	F8, F9
Defective cofactor function of FVIIIa variant	2	65.6×	0.012	F8, F9
Defective F9 variant does not activate FX	2	65.6×	0.012	F8, F9
R-HSA-140877	3	24.6×	0.012	F2, KLKB1, KNG1
Fibrin formation	3	22.7×	0.012	F2, FGA, FGG
Cell surface interactions at the vascular wall	7	5.7×	0.012	F2, THBD, GP6, CD48, GYPB, PROCR, PSG8
Platelet degranulation	7	5.3×	0.013	VWF, F5, F8, FGA, FGG, KNG1, PLEK
p130Cas linkage to MAPK signaling for integrins	3	19.7×	0.015	VWF, FGA, FGG
Defective factor XII causes hereditary angioedema	2	49.2×	0.017	F2, KLKB1
Diseases of hemostasis	2	49.2×	0.017	F2, KLKB1
Aggregated β-amyloid interacts with fibrinogen	2	49.2×	0.017	FGA, FGG
GRB2:SOS provides linkage to MAPK signaling for Integrins	3	18.5×	0.017	VWF, FGA, FGG
Role of phospholipids in phagocytosis	3	11.8×	0.052	ITPR3, PLCG2, PRKCE
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	6	4.5×	0.056	F2, F5, FGA, FGG, IGFBP3, KNG1
Integrin signaling	3	10.9×	0.060	VWF, FGA, FGG
Transport of RCbl within the body	2	24.6×	0.063	TCN2, ABCC1
Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus	2	21.9×	0.077	F2, F9
Gamma-carboxylation of protein precursors	2	19.7×	0.082	F2, F9
Removal of aminoterminal propeptides from gamma-carboxylated proteins	2	19.7×	0.082	F2, F9
Regulation of FXIIa and plasma kallikrein activity	2	19.7×	0.082	KLKB1, KNG1
G alpha (q) signalling events	7	3.5×	0.082	F2, RGSL1, GRK5, KALRN, ITPR3, KNG1, PRKCE
Signaling by high-kinase activity BRAF mutants	3	8.2×	0.104	VWF, FGA, FGG

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 152 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
blood coagulation	10	11.4×	2e-05	F2, THBD, VWF, VKORC1, F5, F8, F9, KLKB1 (+2 more)
thrombin-activated receptor signaling pathway	4	63.4×	1e-04	F2, HPGD, IQGAP2, PLEK
negative regulation of blood coagulation	4	31.7×	0.002	F2, THBD, ADTRP, KNG1
fibrinolysis	4	22.2×	0.006	F2, FGA, FGG, KLKB1
blood coagulation, common pathway	2	110.9×	0.013	THBD, FGA
blood coagulation, fibrin clot formation	3	33.3×	0.013	F2, FGA, FGG
plasminogen activation	3	25.6×	0.026	FGA, FGG, KLKB1
platelet activation	5	8.8×	0.030	F2, VWF, GP6, ITPR3, PLCG2
axon guidance	8	4.8×	0.030	SEMA3D, ROBO4, DPYSL5, CNTN5, CNTN6, EPHA3, KALRN, RELN
electron transport coupled proton transport	2	55.4×	0.045	MT-CYB, MT-ND4
negative regulation of telomere capping	2	44.4×	0.068	SMG6, RAD50
cell-substrate adhesion	3	15.1×	0.077	VWF, CDH11, PRKCE
platelet aggregation	4	8.9×	0.077	GP6, FGA, FGG, PLEK
response to calcium ion	4	8.4×	0.089	FGA, FGG, ITPR3, MT-CYB
zymogen activation	3	13.3×	0.090	THBD, F9, KLKB1
negative regulation of smooth muscle cell proliferation	3	12.3×	0.099	CTNNBIP1, IGFBP3, PPARGC1A
proteolysis	12	2.7×	0.099	F2, THBD, USP54, TMPRSS11D, BRCC3, AGBL1, OVCH2, TMPRSS11F (+4 more)
positive regulation of exocytosis	3	11.9×	0.104	STXBP5, FGA, FGG
negative regulation of platelet activation	2	24.6×	0.125	F2, THBD
cobalamin transport	2	24.6×	0.125	TCN2, ABCC1
regulation of potassium ion transport	2	24.6×	0.125	KCNG3, ANK3
lipopolysaccharide-mediated signaling pathway	3	10.4×	0.126	LY86, PLCG2, PRKCE
establishment of centrosome localization	2	22.2×	0.142	PARD3B, PKHD1
adenylate cyclase-activating dopamine receptor signaling pathway	2	20.2×	0.152	DRD1, GNAL
lipoxygenase pathway	2	20.2×	0.152	ALOX15B, HPGD
positive regulation of peptide hormone secretion	2	20.2×	0.152	FGA, FGG
regulation of extracellular matrix constituent secretion	1	110.9×	0.157	RIC1
toxin catabolic process	1	110.9×	0.157	PRKCE
positive regulation of macromolecule biosynthetic process	1	110.9×	0.157	MTPN
spinal cord patterning	1	110.9×	0.157	RELN

Therapeutics

Drugs indicated for this disease

5 approved, 13 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Apixaban	Approved (phase 4)
Betrixaban	Approved (phase 4)
Dalteparin Sodium	Approved (phase 4)
Enoxaparin Sodium	Approved (phase 4)
Rivaroxaban	Approved (phase 4)
Abelacimab	Phase 3 (in late-stage trials)
Aspirin	Phase 3 (in late-stage trials)
Dabigatran	Phase 3 (in late-stage trials)
Dabigatran Etexilate	Phase 3 (in late-stage trials)
Darexaban	Phase 3 (in late-stage trials)
Edoxaban	Phase 3 (in late-stage trials)
Fondaparinux	Phase 3 (in late-stage trials)
Heparin	Phase 3 (in late-stage trials)
Heparin Sodium	Phase 3 (in late-stage trials)
Nadroparin Calcium	Phase 3 (in late-stage trials)
Semuloparin Sodium	Phase 3 (in late-stage trials)
Sulodexide	Phase 3 (in late-stage trials)
Warfarin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Clopidogrel, Rosuvastatin, Tirofiban.

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 7 · Undrugged: 68

Druggability breadth: 57 of 182 evidence-associated genes (31%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
F2	INDIGOTINDISULFONATE
SLC10A2	URSODIOL
GP6	VALSARTAN
VKORC1	WARFARIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
F2	48	4
SLC10A2	9	4
GP6	9	4
SLC19A2	1	2
SRRM2	1	2
NUP205	1	2
VKORC1	1	4
RIT2	0	0
BCL7A	0	0
SEMA3D	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INDIGOTINDISULFONATE	4	F2
ARGATROBAN	4	F2
BENZOYL PEROXIDE	4	F2
SUCCIMER	4	F2
EDOXABAN	4	F2
METHYLPREDNISOLONE ACETATE	4	F2
LIOTHYRONINE	4	F2
CAPTOPRIL	4	F2
RIVAROXABAN	4	F2
TELOTRISTAT	4	F2
LUSUTROMBOPAG	4	F2
APIXABAN	4	F2
HEXAMIDINE	4	F2
MELAGATRAN	4	F2
CIANIDANOL	4	F2
BORTEZOMIB	4	F2
DEQUALINIUM	4	F2
SULFAGUANIDINE	4	F2
BETRIXABAN	4	F2
XIMELAGATRAN	4	F2
BIVALIRUDIN	4	F2
DABIGATRAN ETEXILATE	4	F2
PENTAMIDINE	4	F2
GENTIAN VIOLET	4	F2
URSODIOL	4	SLC10A2
CYCLOSPORINE	4	SLC10A2
MARALIXIBAT CHLORIDE	4	SLC10A2
CHENODIOL	4	SLC10A2
TAURURSODIOL	4	SLC10A2
MARALIXIBAT	4	SLC10A2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 8.

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

Symbol	Assays	Type breakdown
F2	1,269	Binding:1216, Functional:38, ADMET:13, Toxicity:2
SLC10A2	47	Binding:28, Functional:19
GP6	32	Binding:32
KCNG3	21	Binding:20, Toxicity:1
VWF	17	Binding:17
TMPRSS11D	10	Binding:10
SRRM2	7	Binding:7
NUP205	7	Binding:7
GEMIN5	7	Binding:7
SNRNP70	6	Binding:6
SCD5	6	Binding:6
ANTXR2	3	Binding:3
VKORC1	3	Binding:3
SLC19A2	2	Functional:1, Binding:1
CTNNBIP1	2	Binding:2
TRPM3	2	Binding:2
BCOR	2	Binding:2
BCL7A	1	Binding:1
MTPN	1	Binding:1
TSPOAP1	1	Binding:1
BRCC3	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
F2	3.4.21.5	thrombin
TGM4	2.3.2.13	protein-glutamine gamma-glutamyltransferase
POLE4	2.7.7.7	DNA-directed DNA polymerase
ST6GALNAC3	2.4.99.7	alpha-N-acetylneuraminyl-2,3-beta-galactosyl-1,3-N-acetylgalactosaminide 6-alpha-sialyltransferase
SCD5	1.14.19.1	stearoyl-CoA 9-desaturase
CYP4V2	1.14.14.79	docosahexaenoic acid omega-hydroxylase
VKORC1	1.17.4.4	vitamin-K-epoxide reductase (warfarin-sensitive)
TMPRSS11D	3.4.21.B61

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
F2	1,269

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
VKORC1	1

Chemical tractability of cohort targets

24 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
INDIGOTINDISULFONATE	4	F2
BENZOYL PEROXIDE	4	F2
SUCCIMER	4	F2
METHYLPREDNISOLONE ACETATE	4	F2
LIOTHYRONINE	4	F2
CAPTOPRIL	4	F2
TELOTRISTAT	4	F2
LUSUTROMBOPAG	4	F2
HEXAMIDINE	4	F2
MELAGATRAN	4	F2
CIANIDANOL	4	F2
BORTEZOMIB	4	F2
DEQUALINIUM	4	F2
SULFAGUANIDINE	4	F2
XIMELAGATRAN	4	F2
BIVALIRUDIN	4	F2
PENTAMIDINE	4	F2
GENTIAN VIOLET	4	F2
URSODIOL	4	SLC10A2
CYCLOSPORINE	4	SLC10A2
MARALIXIBAT CHLORIDE	4	SLC10A2
CHENODIOL	4	SLC10A2
TAURURSODIOL	4	SLC10A2
MARALIXIBAT	4	SLC10A2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	F2, SLC10A2, GP6, VKORC1
B	Phased (≥1) drug, not yet approved	3	SLC19A2, SRRM2, NUP205
C	Druggable family + PDB, no drug	9	C4BPA, CD48, TRPM3, ADGRL2, NME7, CNTN5, USP54, TMPRSS11D, BRCC3
D	Druggable family + AlphaFold only, no drug	13	SEMA3D, BTNL2, TGM4, TSPOAP1, ROBO4, KCNG3, POLE4, CORIN, ST6GALNAC3, CATSPERB (+3 more)
E	Difficult family or no structure, no drug	46	RIT2, BCL7A, SNRNP70, SPRY2, STX10, TCN2, THBD, TNFSF13B, CEP41, LCA5L (+36 more)

Undrugged target profiles

68 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
RIT2	0	—
BCL7A	1	—
SEMA3D	0	—
SNRNP70	6	—
SPRY2	0	—
BTNL2	0	—
STX10	0	—
TCN2	0	—
TGM4	0	—
THBD	0	—
TNFSF13B	0	—
CEP41	0	—
LCA5L	0	—
VWF	17	—
WWOX	0	—
ZNF160	0	—
ZNF71	0	—
C4BPA	0	—
FBXL7	0	—
PARD3B	0	—
MTPN	1	—
CD93	0	—
EDEM2	0	—
ZFP64	0	—
ZFPM2	0	—
CD48	0	—
TSPOAP1	1	—
LY86	0	—
CTNNBIP1	2	—
SLC44A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 549.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	315
PHASE3	93
PHASE4	54
PHASE2	54
PHASE2/PHASE3	12
PHASE1	11
EARLY_PHASE1	8
PHASE1/PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03244020	PHASE4	ENROLLING_BY_INVITATION	LMWH vs Aspirin for VTE Prophylaxis in Orthopaedic Oncology
NCT04263038	PHASE4	RECRUITING	Clinical Surveillance vs. Anticoagulation for Low-risk Patients With Isolated Subsegmental Pulmonary Embolism
NCT05735639	PHASE4	RECRUITING	THRomboprophylaxis in Individuals Undergoing Superficial endoVEnous Treatment (THRIVE)
NCT06452342	PHASE4	NOT_YET_RECRUITING	TRanEXamic Acid to Decrease Heavy Menstrual Bleeding in Individuals Anticoagulated for Venous Thromboembolism Pilot Study
NCT06523959	PHASE4	RECRUITING	Avoiding Risks of Thrombosis and Bleeding in Surgery (ARTS) Trial
NCT06581965	PHASE4	RECRUITING	inDividual, Targeted thrombosIS Prophylaxis Versus the Standard ‘One Size Fits All’ Approach in Patients Undergoing Total hIp or Total kNee replaCemenT
NCT06603870	PHASE4	RECRUITING	Secondary Prevention of VTE in Patients With Cancer and Catheter-Related Upper Extremity Deep Vein Thrombosis
NCT06845423	PHASE4	RECRUITING	Prevention of Postpartum Venous Thromboembolism in Women at Intermediate Risk
NCT06958588	PHASE4	RECRUITING	Pulsed Electromagnetic Field Therapy or Pneumatic Compression VTE Prophylaxis
NCT07189897	PHASE4	RECRUITING	Apixaban or Enoxaparin After Head and Neck Cancer Surgery
NCT07303816	PHASE4	NOT_YET_RECRUITING	Statins to Prevent Cancer Associated Blood Clots
NCT00077753	PHASE4	COMPLETED	EXCLAIM:Extended Prophylaxis for Venous ThromboEmbolism (VTE) in Acutely Ill Medical Patients With Prolonged Immobilization
NCT00196118	PHASE4	COMPLETED	Study of IVC Filter Retrieval With the Günther Tulip Vena Cava Filter
NCT00437697	PHASE4	TERMINATED	Thromboprophylaxis in Critically Ill Patients
NCT00445328	PHASE4	TERMINATED	Dalteparin vs Unfractionated Heparin For The Prevention Of Venous Thromboembolism (VTE) In Hospitalized Acutely Ill Medical Patients
NCT00689520	PHASE4	COMPLETED	Long-Term Low-Molecular-Weight Heparin Versus Oral Anticoagulants in Deep Venous Thrombosis
NCT00851864	PHASE4	COMPLETED	Safety and Efficacy of Therapeutic Anticoagulation With Tinzaparin During Pregnancy Via Weight-based Dosing
NCT00966277	PHASE4	COMPLETED	Dalteparin for Primary Venous Thromboembolism (VTE) Prophylaxis in Pancreatic Cancer Patients
NCT00967304	PHASE4	COMPLETED	Clinical Decision Rule Validation Study to Predict Low Recurrent Risk in Patients With Unprovoked Venous Thromboembolism
NCT01119261	PHASE4	COMPLETED	EUropean Pharmacogenetics of AntiCoagulant Therapy - Acenocoumarol
NCT01119274	PHASE4	COMPLETED	EUropean Pharmacogenetics of AntiCoagulant Therapy - Phenprocoumon
NCT01119300	PHASE4	COMPLETED	EUropean Pharmacogenetics of AntiCoagulant Therapy - Warfarin
NCT01210755	PHASE4	COMPLETED	Study in Healthy Volunteers of the Reversion by Haemostatic Drugs of the Anticoagulant Effect of New Anti-thrombotics
NCT01304108	PHASE4	COMPLETED	Improving Venous Thromboembolism Prophylaxis
NCT01467583	PHASE4	COMPLETED	Fondaparinux in Critically Ill Patients With Renal Failure
NCT01916707	PHASE4	UNKNOWN	Weight Based Enoxaparin in Trauma Patients
NCT02095509	PHASE4	COMPLETED	Pharmacokinetics of Enoxaparin in Intensive Care Patients
NCT02396732	PHASE4	TERMINATED	Aspirin and Enoxaparin for VTE in Trauma
NCT02412982	PHASE4	COMPLETED	Evaluation of Venous Thromboembolism Prevention in High-Risk Trauma Patients
NCT02464969	PHASE4	COMPLETED	Apixaban for the Acute Treatment of Venous Thromboembolism in Children
NCT02474212	PHASE4	COMPLETED	: Pharmacokinetics of Enoxaparin After Coronary Artery Bypass Graft Surgery
NCT02559856	PHASE4	COMPLETED	Comparison of Bleeding Risk Between Rivaroxaban and Apixaban: The Pilot Study
NCT02856295	PHASE4	COMPLETED	anti10a Levels in Women Treated With LMWH in the Postpartum Period
NCT02945280	PHASE4	TERMINATED	Apixaban for Routine Management of Upper Extremity Deep Venous Thrombosis
NCT02958969	PHASE4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03006562	PHASE4	TERMINATED	PREvention of VENous ThromboEmbolism Following Radical Prostatectomy
NCT03158792	PHASE4	COMPLETED	Enoxaparin 20mg Versus 30mg Subcutaneously Once Daily in Elderly Patients With Impaired Renal Function
NCT03196349	PHASE4	TERMINATED	Comparison of Oral Anticoagulants for Extended VEnous Thromboembolism
NCT03266783	PHASE4	COMPLETED	Comparison of Bleeding Risk Between Rivaroxaban and Apixaban for the Treatment of Acute Venous Thromboembolism
NCT03426982	PHASE4	UNKNOWN	Comparision Between Activated Partial Thromboplastin Time Versus Anti-Xa Activity in Heparin Monitoring

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ENOXAPARIN SODIUM	4	62
FONDAPARINUX	4	29
DABIGATRAN ETEXILATE	4	21
APIXABAN	4	19
DALTEPARIN SODIUM	4	17
RIVAROXABAN	4	16
EDOXABAN	4	14
WARFARIN	4	6
NADROPARIN CALCIUM	4	4
HEPARIN	4	3
TINZAPARIN SODIUM	4	3
ACENOCOUMAROL	4	2
ARGATROBAN	4	1
BETRIXABAN	4	1
CLARITHROMYCIN	4	1
PHENPROCOUMON	4	1
DABIGATRAN	3	8
SEMULOPARIN SODIUM	3	8
DAREXABAN	3	7
TINZAPARIN	3	5
ABELACIMAB	3	2
BEMIPARIN	3	2
SULODEXIDE	3	1
ANTI-PSGL-1 ANTIBODY SELK2	2	1
GW813893	2	1
LETAXABAN	2	1
ODIPARCIL	2	1
SR-123781A	2	1
ONO-7684	1	1
ENOXAPARIN	0	23