Thrombocytopenia

Summary

Thrombocytopenia (MONDO:0002049) is a disease (an umbrella term covering 6 Mondo subtypes) with 75 cohort genes and 240 clinical trials. The dominant Reactome pathway is Regulation of clotting cascade (14 cohort genes). Top therapeutic interventions include eltrombopag, avatrombopag, and romiplostim.

At a glance

• Umbrella term: 6 Mondo subtypes
• Cohort genes: 75
• ClinVar variants: 340
• Clinical trials: 240

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	thrombocytopenia
Mondo ID	MONDO:0002049
MeSH	D013921
DOID	DOID:1588
ICD-11	683583694
NCIT	C3408
SNOMED CT	302215000
UMLS	C0040034
MedGen	52737
Is cancer (heuristic)	no

Also known as: platelet count decreased · thrombocytopenic disorder

Data availability: 340 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood platelet disease › thrombocytopenia

Related subtypes (4): inherited bleeding disorder, platelet-type, qualitative platelet defect, thrombocytosis disease, TPM4-related platelet disorder

Subtypes (6): acquired thrombocytopenia, thrombocytopenia due to immune destruction, autoimmune thrombocytopenia, neonatal thrombocytopenia, thrombocytopenic purpura, inherited thrombocytopenia

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

340 retrieved; paginated sample, class counts are floors:

129 uncertain significance, 48 conflicting classifications of pathogenicity, 45 likely pathogenic, 42 pathogenic, 28 benign, 24 pathogenic/likely pathogenic, 11 benign/likely benign, 10 likely benign, 1 conflicting classifications of pathogenicity; risk factor, 1 conflicting classifications of pathogenicity; association, 1 pathogenic/likely pathogenic; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
267883	46;X;inv(X)(p11.4q24)dn		Pathogenic	criteria provided, single submitter
626995	NM_001130004.2(ACTN1):c.136C>T (p.Arg46Trp)	ACTN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
988818	NM_139027.6(ADAMTS13):c.1315G>T (p.Glu439Ter)	ADAMTS13	Pathogenic	no assertion criteria provided
30853	NM_014915.3(ANKRD26):c.-134G>A	ANKRD26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
626941	NM_014915.3(ANKRD26):c.-126T>C	ANKRD26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
626943	NM_014915.3(ANKRD26):c.-127A>T	ANKRD26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
627410	NM_014915.3(ANKRD26):c.-118C>T	ANKRD26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812726	NM_014915.3(ANKRD26):c.-118C>A	ANKRD26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812727	NM_014915.3(ANKRD26):c.-128G>A	ANKRD26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812728	NM_014915.3(ANKRD26):c.-128G>T	ANKRD26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812918	NC_000021.8:g.36323351_37470324del	CBR1	Pathogenic	no assertion criteria provided
812913	NC_000021.8:g.35304341_36865875del	CLIC6	Pathogenic	reviewed by expert panel
523249	GRCh37/hg19 15q11.2(chr15:22765628-23300287)	CYFIP1	Pathogenic	criteria provided, single submitter
162220	NM_001987.5(ETV6):c.1195C>T (p.Arg399Cys)	ETV6	Pathogenic	criteria provided, multiple submitters, no conflicts
162221	NM_001987.5(ETV6):c.1106G>A (p.Arg369Gln)	ETV6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
162222	NM_001987.5(ETV6):c.641C>T (p.Pro214Leu)	ETV6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
190240	NM_001987.4(ETV6):c.1153-5_1153-1del	ETV6	Pathogenic	criteria provided, single submitter
626971	NM_001987.5(ETV6):c.1105C>T (p.Arg369Trp)	ETV6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11891	NM_000128.4(F11):c.403G>T (p.Glu135Ter)	F11	Pathogenic	criteria provided, multiple submitters, no conflicts
424634	NM_002017.5(FLI1):c.992_995del (p.Asn331fs)	FLI1	Pathogenic/Likely pathogenic	no assertion criteria provided
10424	NM_002049.4(GATA1):c.653A>G (p.Asp218Gly)	GATA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4290	NM_000157.4(GBA1):c.1226A>G (p.Asn409Ser)	GBA1	Pathogenic/Likely pathogenic; risk factor	criteria provided, multiple submitters, no conflicts
4327	NM_000157.4(GBA1):c.1246G>A (p.Gly416Ser)	GBA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
988821	NM_001377304.1(GFI1B):c.814+1G>A	GFI1B	Pathogenic	no assertion criteria provided
4155	NM_000173.7(GP1BA):c.763A>G (p.Met255Val)	GP1BA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
626958	NM_000173.7(GP1BA):c.344T>C (p.Leu115Pro)	GP1BA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
627183	NM_000173.7(GP1BA):c.745G>A (p.Gly249Ser)	GP1BA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
988865	NM_000173.7(GP1BA):c.1274_1275del (p.Glu425fs)	GP1BA	Pathogenic	criteria provided, single submitter
627237	NM_000407.5(GP1BB):c.143C>A (p.Ser48Ter)	GP1BB	Pathogenic	criteria provided, multiple submitters, no conflicts
13529	NM_000174.5(GP9):c.182A>G (p.Asn61Ser)	GP9	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 161 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TLN1	Limited	Autosomal dominant	thrombocytopenia	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RUNX1	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
RUNX1	Orphanet:521	Chronic myeloid leukemia
RUNX1	Orphanet:71290	Familial platelet disorder with associated myeloid malignancy
RUNX1	Orphanet:98850	Aggressive systemic mastocytosis
SRC	Orphanet:480851	Hereditary thrombocytopenia with early-onset myelofibrosis
STXBP2	Orphanet:540	Familial hemophagocytic lymphohistiocytosis
TBXAS1	Orphanet:1802	Ghosal hematodiaphyseal dysplasia
THBD	Orphanet:436169	Thrombomodulin-related bleeding disorder
THBD	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
THPO	Orphanet:329319	Thrombocythemia with distal limb defects
THPO	Orphanet:3319	Congenital amegakaryocytic thrombocytopenia
THPO	Orphanet:397692	Hereditary isolated aplastic anemia
THPO	Orphanet:71493	Familial thrombocytosis
TPM4	Orphanet:140957	Autosomal dominant macrothrombocytopenia
TPM4	Orphanet:178342	Inflammatory myofibroblastic tumor
TPP2	Orphanet:444463	Autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome due to TPP2 deficiency
VPS33B	Orphanet:2697	Arthrogryposis-renal dysfunction-cholestasis 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
WAS	Orphanet:852	X-linked thrombocytopenia with normal platelets
WAS	Orphanet:86788	X-linked severe congenital neutropenia
WAS	Orphanet:906	Wiskott-Aldrich syndrome
NSD2	Orphanet:280	Wolf-Hirschhorn syndrome
ACTB	Orphanet:2995	Baraitser-Winter cerebrofrontofacial syndrome
ACTB	Orphanet:64755	Becker nevus syndrome
ACTB	Orphanet:673556	Pseudomyogenic hemangioendothelioma
ACTB	Orphanet:674653	Actinomyopathy-associated syndromic thrombocytopenia
ACTB	Orphanet:79107	Developmental malformations-deafness-dystonia syndrome
ADAMTS13	Orphanet:93583	Congenital thrombotic thrombocytopenic purpura
ABCG5	Orphanet:2882	Sitosterolemia
ABCG5	Orphanet:391665	Homozygous familial hypercholesterolemia
ABCG8	Orphanet:2882	Sitosterolemia
ABCG8	Orphanet:391665	Homozygous familial hypercholesterolemia
C1QTNF5	Orphanet:67042	Late-onset retinal degeneration
GP6	Orphanet:98885	Bleeding diathesis due to glycoprotein VI deficiency
HPS3	Orphanet:231512	Hermansky-Pudlak syndrome due to BLOC-2 deficiency
MED12L	Orphanet:528084	Non-specific syndromic intellectual disability
TUBB1	Orphanet:140957	Autosomal dominant macrothrombocytopenia
ACTN1	Orphanet:140957	Autosomal dominant macrothrombocytopenia
SLC45A2	Orphanet:79435	Oculocutaneous albinism type 4
HPS5	Orphanet:231512	Hermansky-Pudlak syndrome due to BLOC-2 deficiency
ACVRL1	Orphanet:275777	Heritable pulmonary arterial hypertension
ACVRL1	Orphanet:774	Hereditary hemorrhagic telangiectasia
P2RY12	Orphanet:36355	Bleeding disorder due to P2Y12 defect
MCFD2	Orphanet:35909	Combined deficiency of factor V and factor VIII
MASTL	Orphanet:168629	Autosomal thrombocytopenia with normal platelets

Cohort genes → proteins

75 cohort genes, 74 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	75

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TLN1	HGNC:11845	ENSG00000137076	Q9Y490	Talin-1	gencc
RUNX1	HGNC:10471	ENSG00000159216	Q01196	Runt-related transcription factor 1	clinvar
SRC	HGNC:11283	ENSG00000197122	P12931	Proto-oncogene tyrosine-protein kinase Src	clinvar
STXBP2	HGNC:11445	ENSG00000076944	Q15833	Syntaxin-binding protein 2	clinvar
TBXAS1	HGNC:11609	ENSG00000059377	P24557	Thromboxane-A synthase	clinvar
THBD	HGNC:11784	ENSG00000178726	P07204	Thrombomodulin	clinvar
THPO	HGNC:11795	ENSG00000090534	P40225	Thrombopoietin	clinvar
TPM4	HGNC:12013	ENSG00000167460	P67936	Tropomyosin alpha-4 chain	clinvar
TPP2	HGNC:12016	ENSG00000134900	P29144	Tripeptidyl-peptidase 2	clinvar
VPS33B	HGNC:12712	ENSG00000184056	Q9H267	Vacuolar protein sorting-associated protein 33B	clinvar
VWF	HGNC:12726	ENSG00000110799	P04275	von Willebrand factor	clinvar
WAS	HGNC:12731	ENSG00000015285	P42768	Actin nucleation-promoting factor WAS	clinvar
NSD2	HGNC:12766	ENSG00000109685	O96028	Histone-lysine N-methyltransferase NSD2	clinvar
ZNF160	HGNC:12948	ENSG00000170949	Q9HCG1	Zinc finger protein 160	clinvar
ACTB	HGNC:132	ENSG00000075624	P60709	Actin, cytoplasmic 1	clinvar
ADAMTS13	HGNC:1366	ENSG00000160323	Q76LX8	A disintegrin and metalloproteinase with thrombospondin motifs 13	clinvar
CYFIP1	HGNC:13759	ENSG00000273749	Q7L576	Cytoplasmic FMR1-interacting protein 1	clinvar
ABCG5	HGNC:13886	ENSG00000138075	Q9H222	ATP-binding cassette sub-family G member 5	clinvar
ABCG8	HGNC:13887	ENSG00000143921	Q9H221	ATP-binding cassette sub-family G member 8	clinvar
MPIG6B	HGNC:13937	ENSG00000204420	O95866	Megakaryocyte and platelet inhibitory receptor G6b	clinvar
C1QTNF5	HGNC:14344	ENSG00000223953	Q9BXJ0	Complement C1q tumor necrosis factor-related protein 5	clinvar
GP6	HGNC:14388	ENSG00000088053	Q9HCN6	Platelet glycoprotein VI	clinvar
CBR1	HGNC:1548	ENSG00000159228	P16152	Carbonyl reductase [NADPH] 1	clinvar
HPS3	HGNC:15597	ENSG00000163755	Q969F9	BLOC-2 complex member HPS3	clinvar
MED12L	HGNC:16050	ENSG00000144893	Q86YW9	Mediator of RNA polymerase II transcription subunit 12-like protein	clinvar
TUBB1	HGNC:16257	ENSG00000101162	Q9H4B7	Tubulin beta-1 chain	clinvar
ACTN1	HGNC:163	ENSG00000072110	P12814	Alpha-actinin-1	clinvar
SLC45A2	HGNC:16472	ENSG00000164175	Q9UMX9	Membrane-associated transporter protein	clinvar
HPS5	HGNC:17022	ENSG00000110756	Q9UPZ3	BLOC-2 complex member HPS5	clinvar
ACVRL1	HGNC:175	ENSG00000139567	P37023	Activin receptor type-1-like	clinvar
P2RY12	HGNC:18124	ENSG00000169313	Q9H244	P2Y purinoceptor 12	clinvar
MCFD2	HGNC:18451	ENSG00000180398	Q8NI22	Multiple coagulation factor deficiency protein 2	clinvar
MASTL	HGNC:19042	ENSG00000120539	Q96GX5	Serine/threonine-protein kinase greatwall	clinvar
LYST	HGNC:1968	ENSG00000143669	Q99698	Lysosomal-trafficking regulator	clinvar
CYCS	HGNC:19986	ENSG00000172115	P99999	Cytochrome c	clinvar
CLIC6	HGNC:2065	ENSG00000159212	Q96NY7	Chloride intracellular channel protein 6	clinvar
COL4A4	HGNC:2206	ENSG00000081052	P53420	Collagen alpha-4(IV) chain	clinvar
COL5A1	HGNC:2209	ENSG00000130635	P20908	Collagen alpha-1(V) chain	clinvar
COL5A2	HGNC:2210	ENSG00000204262	P05997	Collagen alpha-2(V) chain	clinvar
ACBD5	HGNC:23338	ENSG00000107897	Q5T8D3	Acyl-CoA-binding domain-containing protein 5	clinvar
GNE	HGNC:23657	ENSG00000159921	Q9Y223	Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase	clinvar
ERCC6L2	HGNC:26922	ENSG00000182150	Q5T890	DNA excision repair protein ERCC-6-like 2	clinvar
ANKRD26	HGNC:29186	ENSG00000107890	Q9UPS8	Ankyrin repeat domain-containing protein 26	clinvar
NBEAL2	HGNC:31928	ENSG00000160796	Q6ZNJ1	Neurobeachin-like protein 2	clinvar
SLFN14	HGNC:32689	ENSG00000236320	P0C7P3	Protein SLFN14	clinvar
ETV6	HGNC:3495	ENSG00000139083	P41212	Transcription factor ETV6	clinvar
MECOM	HGNC:3498	ENSG00000085276	Q03112	Histone-lysine N-methyltransferase MECOM	clinvar
F10	HGNC:3528	ENSG00000126218	P00742	Coagulation factor X	clinvar
F11	HGNC:3529	ENSG00000088926	P03951	Coagulation factor XI	clinvar
F13A1	HGNC:3531	ENSG00000124491	P00488	Coagulation factor XIII A chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TLN1	Talin-1	High molecular weight cytoskeletal protein concentrated at regions of cell-matrix and cell-cell contacts.
RUNX1	Runt-related transcription factor 1	Forms the heterodimeric complex core-binding factor (CBF) with CBFB.
SRC	Proto-oncogene tyrosine-protein kinase Src	Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G…
STXBP2	Syntaxin-binding protein 2	Involved in intracellular vesicle trafficking and vesicle fusion with membranes.
TBXAS1	Thromboxane-A synthase	Catalyzes the conversion of prostaglandin H2 (PGH2) to thromboxane A2 (TXA2), a potent inducer of blood vessel constriction and platelet aggregation.
THBD	Thrombomodulin	Endothelial cell receptor that plays a critical role in regulating several physiological processes including hemostasis, coagulation, fibrinolysis, inflammation, and angiogenesis.
THPO	Thrombopoietin	Lineage-specific cytokine affecting the proliferation and maturation of megakaryocytes from their committed progenitor cells.
TPM4	Tropomyosin alpha-4 chain	Binds to actin filaments in muscle and non-muscle cells.
TPP2	Tripeptidyl-peptidase 2	Cytosolic tripeptidyl-peptidase that releases N-terminal tripeptides from polypeptides and is a component of the proteolytic cascade acting downstream of the 26S proteasome in the ubiquitin-proteasome pathway.
VPS33B	Vacuolar protein sorting-associated protein 33B	May play a role in vesicle-mediated protein trafficking to lysosomal compartments and in membrane docking/fusion reactions of late endosomes/lysosomes.
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.
WAS	Actin nucleation-promoting factor WAS	Effector protein for Rho-type GTPases that regulates actin filament reorganization via its interaction with the Arp2/3 complex.
NSD2	Histone-lysine N-methyltransferase NSD2	Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at ‘Lys-36’ (H3K36me2).
ZNF160	Zinc finger protein 160	May be involved in transcriptional regulation.
ACTB	Actin, cytoplasmic 1	Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells.
ADAMTS13	A disintegrin and metalloproteinase with thrombospondin motifs 13	Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation.
CYFIP1	Cytoplasmic FMR1-interacting protein 1	Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression.
ABCG5	ATP-binding cassette sub-family G member 5	ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg(2+)- and ATP-dependent sterol transport across the cell membrane.
ABCG8	ATP-binding cassette sub-family G member 8	ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg(2+)- and ATP-dependent sterol transport across the cell membrane.
MPIG6B	Megakaryocyte and platelet inhibitory receptor G6b	Inhibitory receptor that acts as a critical regulator of hematopoietic lineage differentiation, megakaryocyte function and platelet production.
GP6	Platelet glycoprotein VI	Collagen receptor involved in collagen-induced platelet adhesion and activation.
CBR1	Carbonyl reductase [NADPH] 1	NADPH-dependent reductase with broad substrate specificity.
HPS3	BLOC-2 complex member HPS3	Involved in early stages of melanosome biogenesis and maturation.
MED12L	Mediator of RNA polymerase II transcription subunit 12-like protein	May be a component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
TUBB1	Tubulin beta-1 chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.
ACTN1	Alpha-actinin-1	F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures.
SLC45A2	Membrane-associated transporter protein	Proton-associated glucose and sucrose transporter.
HPS5	BLOC-2 complex member HPS5	May regulate the synthesis and function of lysosomes and of highly specialized organelles, such as melanosomes and platelet dense granules.
ACVRL1	Activin receptor type-1-like	Type I receptor for TGF-beta family ligands BMP9/GDF2 and BMP10 and important regulator of normal blood vessel development.
P2RY12	P2Y purinoceptor 12	Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system.
MCFD2	Multiple coagulation factor deficiency protein 2	The MCFD2-LMAN1 complex forms a specific cargo receptor for the ER-to-Golgi transport of selected proteins.
MASTL	Serine/threonine-protein kinase greatwall	Serine/threonine kinase that plays a key role in M phase by acting as a regulator of mitosis entry and maintenance.
LYST	Lysosomal-trafficking regulator	Adapter protein that regulates and/or fission of intracellular vesicles such as lysosomes.
CYCS	Cytochrome c	Electron carrier protein.
CLIC6	Chloride intracellular channel protein 6	In the soluble state, catalyzes glutaredoxin-like thiol disulfide exchange reactions with reduced glutathione as electron donor.
COL4A4	Collagen alpha-4(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
COL5A1	Collagen alpha-1(V) chain	Type V collagen is a member of group I collagen (fibrillar forming collagen).
COL5A2	Collagen alpha-2(V) chain	Type V collagen is a member of group I collagen (fibrillar forming collagen).
ACBD5	Acyl-CoA-binding domain-containing protein 5	Acyl-CoA binding protein which acts as the peroxisome receptor for pexophagy but is dispensable for aggrephagy and nonselective autophagy.
GNE	Bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase	Bifunctional enzyme that possesses both UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase activities, and serves as the initiator of the biosynthetic pathway leading to the production of N-acetylneuraminic acid (NeuAc), a…
ERCC6L2	DNA excision repair protein ERCC-6-like 2	Promotes double-strand break (DSB) end-joining and facilitates programmed recombination by controlling how DNA ends are joined in a spatially oriented manner during repair.
ANKRD26	Ankyrin repeat domain-containing protein 26	Acts as a regulator of adipogenesis.
NBEAL2	Neurobeachin-like protein 2	Probably involved in thrombopoiesis.
SLFN14	Protein SLFN14	Shows no ribosome-associated and endoribonuclease activities.
ETV6	Transcription factor ETV6	Transcriptional repressor; binds to the DNA sequence 5’-CCGGAAGT-3’.
MECOM	Histone-lysine N-methyltransferase MECOM	Functions as a transcriptional regulator binding to DNA sequences in the promoter region of target genes and regulating positively or negatively their expression.
F10	Coagulation factor X	Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
F11	Coagulation factor XI	Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.
F13A1	Coagulation factor XIII A chain	Factor XIII is activated by thrombin and calcium ion to a transglutaminase that catalyzes the formation of gamma-glutamyl-epsilon-lysine cross-links between fibrin chains, thus stabilizing the fibrin clot.
F5	Coagulation factor V	Central regulator of hemostasis.

Protein-family classification

Druggable: 22 · Difficult: 11 · Unknown: 42 · Druggable fraction: 0.29

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
Transporter	3	3.1×	0.361
Protease	5	2.4×	0.361
Antibody/Immunoglobulin	4	1.6×	0.852
Ion channel	1	1.5×	0.892
Kinase	3	1.1×	0.892
Other/Unknown	42	1.0×	0.892
Scaffold/PPI	4	0.9×	0.910
Enzyme (other)	5	0.8×	0.910
Transcription factor	7	0.8×	0.910
GPCR	1	0.3×	0.960

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TLN1	Other/Unknown	no		FERM_domain, IRS_PTB, ILWEQ_dom
RUNX1	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
SRC	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
STXBP2	Other/Unknown	no		Sec1-like, Sec1-like_dom2, Sec1-like_sf
TBXAS1	Other/Unknown	no		Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS
THBD	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, C-type_lectin-like
THPO	Other/Unknown	no		EPO_TPO, Thrombopoietin, 4_helix_cytokine-like_core
TPM4	Other/Unknown	no		Tropomyosin, XRCC4-like_C
TPP2	Protease	yes	3.4.14.10	Peptidase_S8/S53_dom, Peptidase_S8_subtilisin-rel, TPPII_Ig-like-2
VPS33B	Other/Unknown	no		Sec1-like, Sec1-like_dom2, Sec1-like_sf
VWF	Other/Unknown	no		VWF_dom, VWF_type-D, VWF_A
WAS	Other/Unknown	no		CRIB_dom, WH1/EVH1_dom, WH2_dom
NSD2	Transcription factor	no	2.1.1.356	PWWP_dom, SET_dom, Znf_RING
ZNF160	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
ACTB	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
ADAMTS13	Protease	yes	3.4.24.87	TSP1_rpt, Peptidase_M12B, ADAM_Cys-rich
CYFIP1	Other/Unknown	no		Cytoplasmic_FMR1-int, CYRIA/CYRIB_Rac1-bd
ABCG5	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM
ABCG8	Transporter	yes		ABC_transporter-like_ATP-bd, ABC2_TM, ABC_transporter-like_CS
MPIG6B	Other/Unknown	no		G6B, G6B_V-set
C1QTNF5	Other/Unknown	no		C1q_dom, Collagen, Tumour_necrosis_fac-like_dom
GP6	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_fold
CBR1	Enzyme (other)	yes	1.1.1.184	SDR_fam, Sc_DH/Rdtase_CS, NAD(P)-bd_dom_sf
HPS3	Other/Unknown	no		HPS3, HPS3_N, HPS3_C
MED12L	Other/Unknown	no		Mediator_Med12, Mediator_Med12_catenin-bd, Mediator_Med12_LCEWAV
TUBB1	Other/Unknown	no		Tubulin, Beta_tubulin, Tubulin_FtsZ_GTPase
ACTN1	Other/Unknown	no		Actinin_actin-bd_CS, CH_dom, Spectrin_repeat
SLC45A2	Transporter	yes		MFS, MFS_trans_sf
HPS5	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, HPS5, WD40_repeat_dom_sf
ACVRL1	Kinase	yes	2.7.10.2	TGFB_receptor, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
P2RY12	GPCR	yes		GPCR_Rhodpsn, P2Y12_rcpt, GPCR_Rhodpsn_7TM
MCFD2	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
MASTL	Kinase	yes		Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
LYST	Scaffold/PPI	no		BEACH_dom, WD40_rpt, PH-like_dom_sf
CYCS	Other/Unknown	no		Cyt_c_1A/1B, Cyt_c-like_dom, Cyt_c-like_dom_sf
CLIC6	Other/Unknown	no		CLIC, Glutathione-S-Trfase_C-like, Thioredoxin-like_sf
COL4A4	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
COL5A1	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen
COL5A2	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
ACBD5	Other/Unknown	no		Acyl-CoA-binding_protein, FERM/acyl-CoA-bd_prot_sf, ACBD5
GNE	Enzyme (other)	yes	2.7.1.60	ROK, UDP_GlcNAc_Epimerase_2_dom, UDP-GlcNAc_Epase
ERCC6L2	Other/Unknown	no		SNF2_N, Helicase_C-like, DNA/RNA_helicase_DEAH_CS
ANKRD26	Scaffold/PPI	no		Ankyrin_rpt, DUF3496, Ankyrin_rpt-contain_sf
NBEAL2	Scaffold/PPI	no		BEACH_dom, WD40_rpt, ARM-like
SLFN14	Other/Unknown	no		Schlafen_AlbA_2_dom, P-loop_NTPase, Schlafen
ETV6	Other/Unknown	no		Ets_dom, Pointed_dom, SAM/pointed_sf
MECOM	Transcription factor	no		SET_dom, Znf_C2H2_type, Znf_C2H2_sf
F10	Protease	yes	3.4.21.6	EGF-type_Asp/Asn_hydroxyl_site, GLA_domain, EGF
F11	Protease	yes	3.4.21.27	Apple, Trypsin_dom, Peptidase_S1A
F13A1	Antibody/Immunoglobulin	yes	2.3.2.13	Transglutaminase_N, Transglutaminase-like, Transglutaminase_C

Expression context

Cohort genes with no expression data: 0.

67 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)	75
unknown	0

Top tissues across cohort

Tissue	Cohort genes
monocyte	16
leukocyte	15
liver	13
right lobe of liver	12
mononuclear cell	10
tendon of biceps brachii	7
stromal cell of endometrium	5
jejunal mucosa	5
male germ line stem cell (sensu Vertebrata) in testis	5
granulocyte	4
ascending aorta	3
right hemisphere of cerebellum	3
apex of heart	3
pylorus	3
renal medulla	3
pigmented layer of retina	3
popliteal artery	2
tibial artery	2
mucosa of paranasal sinus	2
body of stomach	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TLN1	269	ubiquitous	marker	popliteal artery, tibial artery, ascending aorta
RUNX1	253	ubiquitous	marker	olfactory segment of nasal mucosa, epithelium of bronchus, mucosa of paranasal sinus
SRC	236	ubiquitous	marker	body of stomach, gall bladder, rectum
STXBP2	227	ubiquitous	marker	granulocyte, monocyte, leukocyte
TBXAS1	180	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
THBD	259	ubiquitous	marker	gingival epithelium, gingiva, vena cava
THPO	157	tissue_specific	yes	right lobe of liver, liver, right hemisphere of cerebellum
TPM4	281	ubiquitous	marker	tendon of biceps brachii, stromal cell of endometrium, right coronary artery
TPP2	286	ubiquitous	marker	left testis, right testis, testis
VPS33B	277	ubiquitous	yes	pancreatic ductal cell, Brodmann (1909) area 23, middle temporal gyrus
VWF	289	broad	marker	urethra, tendon of biceps brachii, apex of heart
WAS	246	broad	marker	granulocyte, leukocyte, mononuclear cell
NSD2	281	ubiquitous	marker	ventricular zone, ganglionic eminence, cortical plate
ZNF160	294	ubiquitous	marker	renal medulla, endothelial cell, pylorus
ACTB	295	ubiquitous	marker	urethra, postcentral gyrus, saphenous vein
ADAMTS13	132	tissue_specific	marker	right lobe of liver, liver, right hemisphere of cerebellum
CYFIP1	295	ubiquitous	marker	esophagus squamous epithelium, germinal epithelium of ovary, epithelium of esophagus
ABCG5	61	tissue_specific	marker	jejunal mucosa, right lobe of liver, duodenum
ABCG8	66	tissue_specific	marker	right lobe of liver, liver, jejunal mucosa
MPIG6B	125	tissue_specific	marker	monocyte, leukocyte, blood
C1QTNF5	128	ubiquitous	yes	apex of heart, gall bladder, ascending aorta
GP6	126	tissue_specific	yes	monocyte, leukocyte, male germ line stem cell (sensu Vertebrata) in testis
CBR1	281	ubiquitous	marker	jejunal mucosa, duodenum, C1 segment of cervical spinal cord
HPS3	245	ubiquitous	marker	ileal mucosa, secondary oocyte, jejunal mucosa
MED12L	160	broad	marker	monocyte, leukocyte, adrenal tissue
TUBB1	140	tissue_specific	marker	monocyte, mononuclear cell, leukocyte
ACTN1	292	ubiquitous	marker	blood vessel layer, saphenous vein, ascending aorta
SLC45A2	100	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, pigmented layer of retina, primordial germ cell in gonad
HPS5	134	ubiquitous	marker	sural nerve, male germ line stem cell (sensu Vertebrata) in testis, liver
ACVRL1	221	broad	marker	right lung, upper lobe of left lung, upper lobe of lung

Protein interactions among cohort

Intra-cohort edges: 119.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SRC	11,608
FASN	6,551
FLNA	5,321
VWF	5,204
RUNX1	4,994
GATA1	4,810
TUBB1	4,106
CBR1	3,942
NSD2	3,530
WAS	3,320

Intra-cohort edges

A	B	Sources
ABCG5	ABCG8	biogrid_interaction, intact, string_interaction
ACBD5	ANKRD26	string_interaction
ACBD5	MASTL	biogrid_interaction
ACTB	CLIC6	intact
ACTN1	GFI1B	intact
ACTN1	GNE	intact, string_interaction
ACTN1	SLFN14	string_interaction
ACTN1	SRC	string_interaction
ACTN1	TLN1	string_interaction
ACTN1	TPM4	biogrid_interaction
ADAMTS13	F8	intact, string_interaction
ADAMTS13	GP1BA	string_interaction
ADAMTS13	THBD	string_interaction
ADAMTS13	VWF	intact, string_interaction
ANKRD26	ETV6	string_interaction
ANKRD26	NBEAL2	string_interaction
ANKRD26	RUNX1	string_interaction
ANKRD26	SLFN14	string_interaction
AP3B1	AP3D1	biogrid_interaction, string_interaction
AP3B1	HPS3	string_interaction
AP3B1	HPS5	string_interaction
AP3B1	LYST	string_interaction
AP3B1	STXBP2	string_interaction
AP3D1	HPS3	string_interaction
AP3D1	HPS5	string_interaction
AP3D1	VPS33B	biogrid_interaction
COL5A1	COL5A2	string_interaction
ETV6	MECOM	string_interaction
ETV6	RUNX1	string_interaction
F10	F5	biogrid_interaction, string_interaction
F10	F7	biogrid_interaction, string_interaction
F10	F8	biogrid_interaction, string_interaction
F10	HRG	string_interaction
F10	VWF	string_interaction
F11	F8	string_interaction
F11	GP1BA	string_interaction
F11	THBD	string_interaction
F11	VWF	string_interaction
F13A1	FGA	biogrid_interaction, string_interaction
F13A1	FGB	string_interaction
F13A1	FGG	string_interaction
F13A1	VWF	string_interaction
F5	MCFD2	string_interaction
F7	F8	string_interaction
F7	GGCX	string_interaction
F7	MCFD2	string_interaction
F7	THBD	string_interaction
F7	VWF	string_interaction
F8	GP1BA	string_interaction
F8	GP9	string_interaction

Structural data

PDB: 55 · AlphaFold-only: 19 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
F10	P00742	188
ITGB3	P05106	123
F11	P03951	114
F7	P08709	114
ACTB	P60709	88
SRC	P12931	79
ITGA2B	P08514	78
GBA1	P04062	58
VWF	P04275	48
FGG	P02679	47
ETV6	P41212	44
FGB	P02675	41
FGA	P02671	39
FASN	P49327	34
GGCX	P38435	29
FLNA	P21333	26
F8	P00451	25
NSD2	O96028	22
GP1BA	P07359	22
F5	P12259	18
MCFD2	Q8NI22	17
F13A1	P00488	15
FLI1	Q01543	14
THBD	P07204	13
CYCS	P99999	13
ABCG5	Q9H222	8
ABCG8	Q9H221	8
ACVRL1	P37023	7
WAS	P42768	6
GP6	Q9HCN6	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TPM4	P67936	93.33
TPP2	P29144	91.98
VPS33B	Q9H267	91.82
TBXAS1	P24557	91.50
TUBB1	Q9H4B7	90.92
HPS3	Q969F9	82.67
FLII	Q13045	81.20
SLC45A2	Q9UMX9	77.96
HPS5	Q9UPZ3	73.21
ZNF160	Q9HCG1	68.98
MED12L	Q86YW9	66.04
HRG	P04196	64.90
GFI1B	Q5VTD9	64.09
ANKRD26	Q9UPS8	62.91
HOXA11	P31270	62.09
CLIC6	Q96NY7	60.24
COL5A2	P05997	53.15
LYST	Q99698
NBEAL2	Q6ZNJ1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 550. Enrichment computed across 90 evidence-associated genes (77 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 77 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Regulation of clotting cascade	14	42.4×	4e-17	THBD, VWF, ADAMTS13, F10, F11, F5, F7, F8 (+6 more)
Amplification and propagation of coagulation cascade	10	82.4×	1e-15	VWF, F10, F11, F5, F8, GP1BA, GP1BB, GP9 (+2 more)
Platelet degranulation	16	18.2×	4e-14	STXBP2, TLN1, VWF, ACTN1, F13A1, F5, F8, FGA (+8 more)
p130Cas linkage to MAPK signaling for integrins	8	79.1×	3e-12	SRC, TLN1, VWF, FGA, FGB, FGG, ITGA2B, ITGB3
GRB2:SOS provides linkage to MAPK signaling for Integrins	8	74.2×	4e-12	SRC, TLN1, VWF, FGA, FGB, FGG, ITGA2B, ITGB3
Platelet Aggregation (Plug Formation)	9	51.3×	5e-12	SRC, THPO, VWF, GP1BA, GP1BB, GP9, ITGA2B, ITGB3 (+1 more)
Integrin signaling	9	49.4×	6e-12	SRC, TLN1, VWF, FGA, FGB, FGG, ITGA2B, ITGB3 (+1 more)
Fibrin formation	7	79.9×	5e-11	F13A1, FGA, FGB, FGG, ITGA2B, ITGB3, SERPINC1
Signaling by high-kinase activity BRAF mutants	9	37.1×	9e-11	SRC, TLN1, VWF, ACTB, FGA, FGB, FGG, ITGA2B (+1 more)
MAP2K and MAPK activation	9	33.4×	2e-10	SRC, TLN1, VWF, ACTB, FGA, FGB, FGG, ITGA2B (+1 more)
Signaling by RAF1 mutants	9	32.6×	3e-10	SRC, TLN1, VWF, ACTB, FGA, FGB, FGG, ITGA2B (+1 more)
Signaling by moderate kinase activity BRAF mutants	9	29.7×	5e-10	SRC, TLN1, VWF, ACTB, FGA, FGB, FGG, ITGA2B (+1 more)
Paradoxical activation of RAF signaling by kinase inactive BRAF	9	29.7×	5e-10	SRC, TLN1, VWF, ACTB, FGA, FGB, FGG, ITGA2B (+1 more)
Signaling downstream of RAS mutants	9	29.7×	5e-10	SRC, TLN1, VWF, ACTB, FGA, FGB, FGG, ITGA2B (+1 more)
Signaling by BRAF and RAF1 fusions	10	22.1×	7e-10	SRC, TLN1, VWF, ACTB, FGA, FGB, FGG, AP3B1 (+2 more)
GP1b-IX-V activation signalling	6	74.2×	2e-09	SRC, VWF, FLNA, GP1BA, GP1BB, GP9
Initiation of coagulation cascade	7	43.3×	5e-09	VWF, F10, F5, F7, F8, SERPINC1, PROS1
Platelet Adhesion to exposed collagen	6	52.4×	3e-08	VWF, ADAMTS13, GP6, GP1BA, GP1BB, GP9
Gamma-carboxylation of protein precursors	5	74.2×	8e-08	F10, F7, GGCX, PROS1, PROZ
FXIIa, PKa-dependent activation of coagulation pathway	5	74.2×	8e-08	F11, GP1BA, GP1BB, GP9, KLKB1
Integrin cell surface interactions	9	15.7×	1e-07	VWF, COL4A4, COL5A1, COL5A2, FGA, FGB, FGG, ITGA2B (+1 more)
Defective F9 activation	4	98.9×	7e-07	F11, GP1BA, GP1BB, GP9
Enhanced binding of GP1BA variant to VWF multimer:collagen	4	84.8×	2e-06	VWF, GP1BA, GP1BB, GP9
Defective binding of VWF variant to GPIb:IX:V	4	84.8×	2e-06	VWF, GP1BA, GP1BB, GP9
Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus	4	65.9×	5e-06	F10, F7, PROS1, PROZ
Removal of aminoterminal propeptides from gamma-carboxylated proteins	4	59.3×	8e-06	F10, F7, PROS1, PROZ
Signaling by PDGF	6	19.8×	1e-05	SRC, COL4A4, COL5A1, COL5A2, PLAT, PLG
Aggregated β-amyloid interacts with fibrinogen	3	111.2×	2e-05	FGA, FGB, FGG
FCGR3A-mediated phagocytosis	6	14.6×	6e-05	SRC, WAS, ACTB, CYFIP1, ARPC1B, MYH9
Non-integrin membrane-ECM interactions	6	12.0×	2e-04	ACTB, ACTN1, COL4A4, COL5A1, COL5A2, ITGB3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 88 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	23	45.4×	1e-29	THBD, VWF, WAS, ADAMTS13, MPIG6B, HPS5, F10, F11 (+15 more)
platelet aggregation	12	46.0×	8e-15	TLN1, ACTB, GP6, TUBB1, P2RY12, FGA, FGB, FGG (+4 more)
fibrinolysis	9	86.2×	9e-14	FGA, FGB, FGG, GP1BA, HRG, KLKB1, PLAT, PLG (+1 more)
platelet formation	9	71.8×	4e-13	TPM4, MPIG6B, TUBB1, ACTN1, NBEAL2, GATA1, MPL, MYH9 (+1 more)
megakaryocyte development	9	71.8×	4e-13	THPO, VPS33B, MPIG6B, FLI1, FLNA, GP1BA, GP1BB, GP9 (+1 more)
plasminogen activation	6	88.4×	4e-09	F11, FGA, FGB, FGG, KLKB1, PLAT
platelet activation	9	27.4×	4e-09	SRC, VWF, ADAMTS13, GP6, P2RY12, GP1BA, GP1BB, HRG (+1 more)
blood coagulation, intrinsic pathway	5	119.7×	2e-08	F8, FLNA, GP1BA, GP1BB, GP9
blood coagulation, fibrin clot formation	5	95.8×	8e-08	F13A1, FGA, FGB, FGG, ITGB3
integrin-mediated signaling pathway	8	14.6×	6e-06	SRC, TLN1, ADAMTS13, MPIG6B, ITGA2B, ITGB3, MYH9, PTPN11
negative regulation of fibrinolysis	4	63.8×	3e-05	THBD, HRG, PLAT, PLG
positive regulation of platelet activation	4	58.9×	3e-05	FLNA, GP1BA, GP1BB, GP9
positive regulation of fibrinolysis	3	114.9×	9e-05	F11, KLKB1, PLG
melanosome assembly	4	40.3×	2e-04	HPS3, HPS5, AP3B1, AP3D1
positive regulation of substrate adhesion-dependent cell spreading	5	21.3×	2e-04	FGA, FGB, FGG, FLNA, ITGB3
release of sequestered calcium ion into cytosol	5	19.5×	3e-04	FLNA, GP1BA, GP1BB, GP9, PLCB2
platelet dense granule organization	4	30.6×	4e-04	HPS3, HPS5, AP3B1, AP3D1
hematopoietic stem cell proliferation	4	29.5×	5e-04	RUNX1, ETV6, MECOM, GBA1
regulation of blood coagulation	3	63.8×	5e-04	GP1BA, HRG, SERPINC1
positive regulation of vasoconstriction	4	27.4×	6e-04	TBXAS1, FGA, FGB, FGG
hemostasis	3	57.5×	6e-04	VWF, P2RY12, FLI1
cell-matrix adhesion	6	11.2×	6e-04	ADAMTS13, FGA, FGB, FGG, ITGA2B, ITGB3
positive regulation of peptide hormone secretion	3	52.2×	8e-04	FGA, FGB, FGG
negative regulation of intestinal phytosterol absorption	2	191.5×	8e-04	ABCG5, ABCG8
negative regulation of intestinal cholesterol absorption	2	191.5×	8e-04	ABCG5, ABCG8
blood coagulation, common pathway	2	191.5×	8e-04	THBD, FGA
negative regulation of endodermal cell differentiation	2	191.5×	8e-04	COL5A1, COL5A2
blood circulation	4	23.2×	8e-04	ACVRL1, F5, FLI1, LPA
negative regulation of endothelial cell apoptotic process	4	22.5×	8e-04	FGA, FGB, FGG, ITGB3
positive regulation of heterotypic cell-cell adhesion	3	44.2×	0.001	FGA, FGB, FGG

Therapeutics

Drugs indicated for this disease

11 approved, 16 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Argatroban	Approved (phase 4)
Bivalirudin	Approved (phase 4)
Cortisone Acetate	Approved (phase 4)
Dexamethasone	Approved (phase 4)
Imiglucerase	Approved (phase 4)
Lepirudin	Approved (phase 4)
Lusutrombopag	Approved (phase 4)
Oprelvekin	Approved (phase 4)
Prednisolone	Approved (phase 4)
Prednisone	Approved (phase 4)
Romiplostim	Approved (phase 4)
Avatrombopag	Phase 3 (in late-stage trials)
Azacitidine	Phase 3 (in late-stage trials)
Azathioprine	Phase 3 (in late-stage trials)
Danaparoid Sodium	Phase 3 (in late-stage trials)
Decitabine	Phase 3 (in late-stage trials)
Efgartigimod Alfa	Phase 3 (in late-stage trials)
Eltrombopag	Phase 3 (in late-stage trials)
Hydroxychloroquine	Phase 3 (in late-stage trials)
Ianalumab	Phase 3 (in late-stage trials)
Methylprednisolone	Phase 3 (in late-stage trials)
Nipocalimab	Phase 3 (in late-stage trials)
Rafutrombopag	Phase 3 (in late-stage trials)
Recombinant Human Thrombopoietin	Phase 3 (in late-stage trials)
Rivaroxaban	Phase 3 (in late-stage trials)
Tranexamic Acid	Phase 3 (in late-stage trials)
Warfarin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Acetylcysteine, Daclizumab, Diacerein, Eculizumab, Fondaparinux, Hetrombopag Olamine, Interferon Alfa, Oseltamivir, PEGINTERFERON ALFA-2A, PEGINTERFERON ALFA-2B, Platelets, Ribavirin, Rozanolixizumab, Telaprevir, Tucidinostat.

Drug target analysis

Approved (phase 4): 19 · Phase ≥3: 20 · Phased (≥1): 25 · Undrugged: 50

Druggability breadth: 55 of 90 evidence-associated genes (61%) 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
RUNX1	APOMORPHINE HYDROCHLORIDE
SRC	PONATINIB
TBXAS1	CLOTRIMAZOLE
THPO	PROGESTERONE
NSD2	VENETOCLAX
GP6	VALSARTAN
CBR1	TRICLOSAN
TUBB1	COLCHICINE
ACVRL1	FEDRATINIB
P2RY12	CANGRELOR TETRASODIUM
ETV6	CERITINIB
F10	ARGATROBAN
F11	MELAGATRAN
F5	EDOXABAN
F7	NIACINAMIDE
FASN	RABEPRAZOLE
GBA1	MIGALASTAT
ITGA2B	EPTIFIBATIDE
ITGB3	EPTIFIBATIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SRC	103	4
THPO	103	4
TBXAS1	46	4
F10	23	4
TUBB1	22	4
ITGB3	18	4
ITGA2B	14	4
GBA1	12	4
ACVRL1	11	4
P2RY12	11	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
APOMORPHINE HYDROCHLORIDE	4	RUNX1
PONATINIB	4	SRC
AFATINIB	4	SRC
FEDRATINIB	4	ACVRL1, SRC
TIVOZANIB	4	SRC
SORAFENIB	4	SRC
DASATINIB ANHYDROUS	4	SRC
NICLOSAMIDE	4	SRC, THPO
NERATINIB	4	SRC
INFIGRATINIB PHOSPHATE	4	SRC
INFIGRATINIB	4	SRC
IBRUTINIB	4	GP6, SRC
ENTRECTINIB	4	ACVRL1, SRC
CABOZANTINIB	4	SRC
DACOMITINIB ANHYDROUS	4	SRC
CERITINIB	4	ETV6, SRC
VANDETANIB	4	ACVRL1, SRC
NILOTINIB	4	SRC
BOSUTINIB	4	SRC
BRIGATINIB	4	SRC
REPOTRECTINIB	4	SRC
PAZOPANIB	4	SRC
NINTEDANIB	4	ACVRL1, SRC
SUNITINIB	4	SRC
DASATINIB	4	ACVRL1, SRC
ERLOTINIB	4	SRC
LAPATINIB	4	SRC
TIRBANIBULIN	4	SRC, TUBB1
CRIZOTINIB	4	SRC
MIDOSTAURIN	4	SRC

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 14.

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

Symbol	Assays	Type breakdown
SRC	1,917	Binding:1858, Functional:43, ADMET:16
TUBB1	1,765	Binding:1723, Functional:36, ADMET:6
F10	795	Binding:779, Functional:9, ADMET:7
ITGB3	771	Binding:575, Functional:183, ADMET:13
GBA1	436	Binding:403, Functional:33
ITGA2B	407	Binding:246, Functional:159, ADMET:2
F11	273	Binding:272, ADMET:1
NSD2	264	Binding:256, Functional:8
F7	255	Binding:237, Functional:17, ADMET:1
ACVRL1	213	Binding:207, Functional:3, Toxicity:2, ADMET:1
TBXAS1	210	Binding:138, Functional:72
P2RY12	160	Binding:102, Functional:58
FASN	142	Binding:136, Functional:6
MASTL	44	Binding:44
F13A1	42	Binding:42
CBR1	35	Binding:28, ADMET:7
GP6	32	Binding:32
ACTB	21	Binding:21
RUNX1	20	Binding:17, Functional:3
VWF	17	Binding:17
ETV6	11	Binding:11
CYCS	10	Binding:10
F5	10	Binding:10
TPP2	8	Binding:8
F8	8	Binding:8
AP3B1	8	Binding:8
CYFIP1	7	Binding:7
FLNA	7	Binding:7
FLI1	5	Binding:5
GGCX	5	Binding:5
TPM4	4	Binding:4
ADAMTS13	3	Binding:3
THPO	2	Functional:2
FGB	2	Binding:2
TLN1	1	Binding:1
ACTN1	1	Binding:1
GNE	1	Binding:1
MECOM	1	Binding:1
AP3D1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SRC	2.7.10.2	non-specific protein-tyrosine kinase
TPP2	3.4.14.10	tripeptidyl-peptidase II
NSD2	2.1.1.356, 2.1.1.357, 2.1.1.359	[histone H3]-lysine27 N-trimethyltransferase, [histone H3]-lysine36 N-dimethyltransferase, [histone H3]-lysine36 N-trimethyltransferase
ADAMTS13	3.4.24.87	ADAMTS13 endopeptidase
CBR1	1.1.1.184	carbonyl reductase (NADPH)
ACVRL1	2.7.10.2, 2.7.11.30	non-specific protein-tyrosine kinase, receptor protein serine/threonine kinase
GNE	2.7.1.60, 3.2.1.183, 5.1.3.14	N-acylmannosamine kinase, UDP-N-acetylglucosamine 2-epimerase (hydrolysing), UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing)
F10	3.4.21.6	coagulation factor Xa
F11	3.4.21.27	coagulation factor XIa
F13A1	2.3.2.13	protein-glutamine gamma-glutamyltransferase
F7	3.4.21.21	coagulation factor VIIa
FASN	2.3.1.39, 2.3.1.85	[acyl-carrier-protein] S-malonyltransferase, fatty-acid synthase system
GBA1	3.2.1.45	glucosylceramidase
GGCX	4.1.1.90	peptidyl-glutamate 4-carboxylase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SRC	1,917
TBXAS1	210
NSD2	264
TUBB1	1,765
ACVRL1	213
P2RY12	160
F10	795
F11	273
F7	255
FASN	142
GBA1	436
ITGA2B	407
ITGB3	771

Pharmacogenomics

Cohort genes with a PharmGKB record: 74; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 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)
APOMORPHINE HYDROCHLORIDE	4	RUNX1
PONATINIB	4	SRC
AFATINIB	4	SRC
FEDRATINIB	4	ACVRL1, SRC
TIVOZANIB	4	SRC
SORAFENIB	4	SRC
DASATINIB ANHYDROUS	4	SRC
NICLOSAMIDE	4	SRC, THPO
NERATINIB	4	SRC
INFIGRATINIB PHOSPHATE	4	SRC
INFIGRATINIB	4	SRC
IBRUTINIB	4	GP6, SRC
ENTRECTINIB	4	ACVRL1, SRC
CABOZANTINIB	4	SRC
DACOMITINIB ANHYDROUS	4	SRC
CERITINIB	4	ETV6, SRC
VANDETANIB	4	ACVRL1, SRC
NILOTINIB	4	SRC
BOSUTINIB	4	SRC
BRIGATINIB	4	SRC
REPOTRECTINIB	4	SRC
PAZOPANIB	4	SRC
NINTEDANIB	4	ACVRL1, SRC
SUNITINIB	4	SRC
DASATINIB	4	ACVRL1, SRC
ERLOTINIB	4	SRC
LAPATINIB	4	SRC
TIRBANIBULIN	4	SRC, TUBB1
CRIZOTINIB	4	SRC
MIDOSTAURIN	4	SRC

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	19	RUNX1, SRC, TBXAS1, THPO, NSD2, GP6, CBR1, TUBB1, ACVRL1, P2RY12 (+9 more)
B	Phased (≥1) drug, not yet approved	6	TPP2, ACTB, F13A1, FGB, FLNA, AP3B1
C	Druggable family + PDB, no drug	7	ADAMTS13, ABCG5, ABCG8, MASTL, GNE, GGCX, KCNE2
D	Druggable family + AlphaFold only, no drug	1	SLC45A2
E	Difficult family or no structure, no drug	42	TLN1, STXBP2, THBD, TPM4, VPS33B, VWF, WAS, ZNF160, CYFIP1, MPIG6B (+32 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TLN1	1	FLNA
VWF	17	ITGA2B
MPIG6B	0	GP6
MCFD2	0	F5
LYST	0	AP3B1
ANKRD26	0	ETV6, RUNX1
MECOM	1	RUNX1
F8	8	F10
FGA	0	FGB
FGG	0	FGB
GP1BA	0	FLNA
AP3D1	1	AP3B1
STXBP2	0	—
THBD	0	—
TPM4	4	—
VPS33B	0	—
WAS	0	—
ZNF160	0	—
ADAMTS13	3	—
CYFIP1	7	—
ABCG5	0	—
ABCG8	0	—
C1QTNF5	0	—
HPS3	0	—
MED12L	0	—
ACTN1	1	—
SLC45A2	0	—
HPS5	0	—
MASTL	44	—
CYCS	10	—

Clinical trials & evidence

Clinical trials

Clinical trials: 240.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	90
PHASE2	65
PHASE3	26
PHASE1	19
PHASE4	14
PHASE1/PHASE2	11
PHASE2/PHASE3	10
EARLY_PHASE1	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT06562738	PHASE4	RECRUITING	Clinical Study on Efficacy and Safety of Hetrombopag in the Preoperative Patients of Thrombocytopenia
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients
NCT06202625	PHASE2/PHASE3	RECRUITING	Efficacy and Safety of Avatrombopag in the Treatment of Thrombocytopenia After Haplo-HSCT
NCT06913374	PHASE2/PHASE3	NOT_YET_RECRUITING	The Study of Different Cycles of High-dose Dexamethasone in the Treatment of ITP
NCT07442513	PHASE3	RECRUITING	Comparison of Etamsylate Versus Placebo to Prevent Bleeding in HSCT
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00073580	PHASE3	COMPLETED	Angiomax in Patients With HIT/HITTS Type II Undergoing Off-Pump Coronary Artery Bypass Grafting (CABG) (CHOOSE)
NCT00102323	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
NCT00102336	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy
NCT00116688	PHASE3	COMPLETED	Open Label Extension Study of Romiplostim (AMG 531) in Thrombocytopenic Patients With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
NCT00128713	PHASE3	COMPLETED	Optimal Platelet Dose Strategy for Management of Thrombocytopenia
NCT00151866	PHASE3	COMPLETED	Efficacy of Transfusions With Platelets Stored in Platelet Additive Solution II Versus Plasma
NCT00261924	PHASE3	COMPLETED	Efficacy and Safety Study of Platelets Treated for Pathogen Inactivation and Stored for Up to Seven Days
NCT00415532	PHASE3	COMPLETED	Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura
NCT00420914	PHASE3	TERMINATED	Strategies for Transfusion of Platelets (SToP)
NCT00501345	PHASE3	TERMINATED	Aspirin in Patients With Myocardial Infarction and Thrombocytopenia
NCT00508820	PHASE3	COMPLETED	An Open Label Study of Romiplostim in Adult Thrombocytopenic Subjects With ITP
NCT00678587	PHASE3	TERMINATED	Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures
NCT01368211	PHASE2/PHASE3	TERMINATED	Mirasol-Treated Platelets - (Pathogen Reduction Extended Storage Study)
NCT01428635	PHASE2/PHASE3	COMPLETED	Eltrombopag Olamine in Treating Thrombocytopenia in Patients With Chronic Myeloid Leukemia or Myelofibrosis Receiving Tyrosine Kinase Therapy
NCT01438840	PHASE3	COMPLETED	Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)
NCT01444417	PHASE3	COMPLETED	Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients
NCT01805648	PHASE3	UNKNOWN	Efficacy and Safety Study of Maintenance Treatment With rhTPO in Thrombocytopenic Subjects With ITP
NCT01821625	PHASE2/PHASE3	TERMINATED	Study of Quadruple Therapy With Eltrombopag for Chronic Hepatitis C
NCT02094248	PHASE2/PHASE3	UNKNOWN	rhTPO in Critical Patients With Thrombocytopenia
NCT02241031	PHASE2/PHASE3	UNKNOWN	Megakaryocytic Progenitor Cells for Prophylaxis and Treatment of Thrombocytopenia
NCT02244658	PHASE3	UNKNOWN	Recombinant Human Thrombopoietin (rhTPO) in Management of Chemotherapy-induced Thrombocytopenia in Acute Myelocytic Leukemia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ELTROMBOPAG	4	20
AVATROMBOPAG	4	15
ROMIPLOSTIM	4	14
CYTARABINE	4	4
DECITABINE	4	3
FONDAPARINUX	4	3
MERCAPTOPURINE ANHYDROUS	4	3
FOSTAMATINIB	4	2
ALEMTUZUMAB	4	1
AMINOCAPROIC ACID	4	1
ARGATROBAN	4	1
ASPARAGINASE	4	1
AZACITIDINE	4	1
AZATHIOPRINE	4	1
BUSULFAN	4	1
DACLIZUMAB	4	1
DALTEPARIN SODIUM	4	1
DANAZOL	4	1
DIPYRIDAMOLE	4	1
ECULIZUMAB	4	1
ENOXAPARIN SODIUM	4	1
ETHAMSYLATE	4	1
ETOPOSIDE PHOSPHATE	4	1
HYDROXYCHLOROQUINE	4	1
ISOTRETINOIN	4	1
LUSPATERCEPT	4	1
LUSUTROMBOPAG	4	1
LUTETIUM LU-177 VIPIVOTIDE TETRAXETAN	4	1
MOMELOTINIB	4	1
OFATUMUMAB	4	1