Autosomal dominant macrothrombocytopenia

Summary

Autosomal dominant macrothrombocytopenia (MONDO:0015372) is a disease caused by GP1BB (GenCC Strong), with 9 cohort genes. The dominant Reactome pathway is Platelet Aggregation (Plug Formation) (4 cohort genes).

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: GP1BB (GenCC Strong)
• Cohort genes: 9
• ClinVar variants: 1
• Phenotypes (HPO): 9

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		100	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

9 HPO clinical features (Orphanet curated; top 9 by frequency):

HPO ID	Term	Frequency
HP:0001873	Thrombocytopenia	Very frequent (80-99%)
HP:0011877	Increased mean platelet volume	Very frequent (80-99%)
HP:0040185	Macrothrombocytopenia	Very frequent (80-99%)
HP:0032438	Platelet anisocytosis	Frequent (30-79%)
HP:0000421	Epistaxis	Occasional (5-29%)
HP:0000978	Bruising susceptibility	Occasional (5-29%)
HP:0004846	Prolonged bleeding after surgery	Occasional (5-29%)
HP:0006298	Prolonged bleeding after dental extraction	Occasional (5-29%)
HP:0100608	Metrorrhagia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant macrothrombocytopenia
Mondo ID	MONDO:0015372
Orphanet	140957
SNOMED CT	720521008
UMLS	C4304021
MedGen	929690
GARD	0016965
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant · 10 GenCC gene-disease records.

Disease family

An umbrella term covering 3 Mondo subtypes.

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

Related subtypes (20): thrombocytopenia 2, thrombocytopenia, cyclic, thrombocytopenia 3, congenital thrombotic thrombocytopenic purpura, thrombocytopenia, X-linked, with or without dyserythropoietic anemia, thrombocytopenia 1, thrombocytopenia 4, thrombocytopenia 5, isolated delta-storage pool disease, syndromic constitutional thrombocytopenia, alpha granule disease, thrombocytopenia 7, macrothrombocytopenia, isolated, congenital autosomal recessive small-platelet thrombocytopenia, congenital amegakaryocytic thrombocytopenia, thrombocytopenia 9, thrombocytopenia 10, thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies, thrombocytopenia 12 with or without myopathy, thrombocytopenia 13, syndromic

Subtypes (3): platelet-type bleeding disorder 15, macrothrombocytopenia, isolated, 2, autosomal dominant, macrothrombocytopenia, isolated, 1, autosomal dominant

Genetics & variants

GWAS landscape

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

Variant details and genetic-evidence tiers

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1324499	NM_000407.5(GP1BB):c.423C>A (p.Cys141Ter)	SEPT5-GP1BB	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 59 · Orphanet: 22 · 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
TUBB1	Definitive	Autosomal dominant	macrothrombocytopenia, isolated, 1, autosomal dominant	5
GP1BB	Strong	Autosomal dominant	autosomal dominant macrothrombocytopenia	6
ACTN1	Supportive	Autosomal dominant	autosomal dominant macrothrombocytopenia	5
GFI1B	Supportive	Autosomal dominant	autosomal dominant macrothrombocytopenia	5
GP1BA	Supportive	Autosomal dominant	autosomal dominant macrothrombocytopenia	12
ITGA2B	Supportive	Autosomal dominant	autosomal dominant macrothrombocytopenia	10
ITGB3	Supportive	Autosomal dominant	autosomal dominant macrothrombocytopenia	7
TPM4	Supportive	Autosomal dominant	autosomal dominant macrothrombocytopenia	2
TRPM7	Supportive	Autosomal dominant	autosomal dominant macrothrombocytopenia	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TPM4	Orphanet:140957	Autosomal dominant macrothrombocytopenia
TPM4	Orphanet:178342	Inflammatory myofibroblastic tumor
TUBB1	Orphanet:140957	Autosomal dominant macrothrombocytopenia
ACTN1	Orphanet:140957	Autosomal dominant macrothrombocytopenia
TRPM7	Orphanet:140957	Autosomal dominant macrothrombocytopenia
TRPM7	Orphanet:90020	Parkinson-dementia complex of Guam
GFI1B	Orphanet:140957	Autosomal dominant macrothrombocytopenia
GFI1B	Orphanet:734	Alpha delta granule deficiency
GP1BA	Orphanet:140957	Autosomal dominant macrothrombocytopenia
GP1BA	Orphanet:274	Bernard-Soulier syndrome
GP1BA	Orphanet:52530	Pseudo-von Willebrand disease
GP1BA	Orphanet:853	Fetal and neonatal alloimmune thrombocytopenia
GP1BB	Orphanet:140957	Autosomal dominant macrothrombocytopenia
GP1BB	Orphanet:274	Bernard-Soulier syndrome
GP1BB	Orphanet:567	22q11.2 deletion syndrome
GP1BB	Orphanet:853	Fetal and neonatal alloimmune thrombocytopenia
ITGA2B	Orphanet:140957	Autosomal dominant macrothrombocytopenia
ITGA2B	Orphanet:849	Glanzmann thrombasthenia
ITGA2B	Orphanet:853	Fetal and neonatal alloimmune thrombocytopenia
ITGB3	Orphanet:140957	Autosomal dominant macrothrombocytopenia
ITGB3	Orphanet:849	Glanzmann thrombasthenia
ITGB3	Orphanet:853	Fetal and neonatal alloimmune thrombocytopenia

Cohort genes → proteins

9 cohort genes, 9 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	9

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TPM4	HGNC:12013	ENSG00000167460	P67936	Tropomyosin alpha-4 chain	gencc
TUBB1	HGNC:16257	ENSG00000101162	Q9H4B7	Tubulin beta-1 chain	gencc
ACTN1	HGNC:163	ENSG00000072110	P12814	Alpha-actinin-1	gencc
TRPM7	HGNC:17994	ENSG00000092439	Q96QT4	Transient receptor potential cation channel subfamily M member 7	gencc
GFI1B	HGNC:4238	ENSG00000165702	Q5VTD9	Zinc finger protein Gfi-1b	gencc
GP1BA	HGNC:4439	ENSG00000185245	P07359	Platelet glycoprotein Ib alpha chain	gencc
GP1BB	HGNC:4440	ENSG00000203618	P13224	Platelet glycoprotein Ib beta chain	gencc
ITGA2B	HGNC:6138	ENSG00000005961	P08514	Integrin alpha-IIb	gencc
ITGB3	HGNC:6156	ENSG00000259207	P05106	Integrin beta-3	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TPM4	Tropomyosin alpha-4 chain	Binds to actin filaments in muscle and non-muscle cells.
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.
TRPM7	Transient receptor potential cation channel subfamily M member 7	Bifunctional protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins via its kinase domain.
GFI1B	Zinc finger protein Gfi-1b	Essential proto-oncogenic transcriptional regulator necessary for development and differentiation of erythroid and megakaryocytic lineages.
GP1BA	Platelet glycoprotein Ib alpha chain	GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium.
GP1BB	Platelet glycoprotein Ib beta chain	Gp-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to von Willebrand factor, which is already bound to the subendothelium.
ITGA2B	Integrin alpha-IIb	Integrin alpha-IIb/beta-3 (ITGA2B:ITGB3) is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin.
ITGB3	Integrin beta-3	Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 6 · Druggable fraction: 0.22

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	1	3.2×	0.507
Kinase	1	3.1×	0.507
Other/Unknown	6	1.2×	0.507
Transcription factor	1	0.9×	0.687

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TPM4	Other/Unknown	no		Tropomyosin, XRCC4-like_C
TUBB1	Other/Unknown	no		Tubulin, Beta_tubulin, Tubulin_FtsZ_GTPase
ACTN1	Other/Unknown	no		Actinin_actin-bd_CS, CH_dom, Spectrin_repeat
TRPM7	Kinase	yes		a-kinase_dom, Kinase-like_dom_sf, TRPM7_a-kinase_dom
GFI1B	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
GP1BA	Other/Unknown	no		LRRNT, Cys-rich_flank_reg_C, Leu-rich_rpt
GP1BB	Other/Unknown	no		LRRNT, Cys-rich_flank_reg_C, LRR_dom_sf
ITGA2B	Antibody/Immunoglobulin	yes		Integrin_alpha, FG-GAP, Int_alpha_beta-p
ITGB3	Other/Unknown	no		Integrin_bsu_VWA, Integrin_bsu_tail, EGF_extracell

Expression context

Cohort genes with no expression data: 0.

9 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)	9
unknown	0

Top tissues across cohort

Tissue	Cohort genes
monocyte	6
leukocyte	5
mononuclear cell	4
right coronary artery	1
stromal cell of endometrium	1
tendon of biceps brachii	1
ascending aorta	1
blood vessel layer	1
saphenous vein	1
calcaneal tendon	1
cardiac muscle of right atrium	1
left ventricle myocardium	1
sperm	1
trabecular bone tissue	1
granulocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TPM4	281	ubiquitous	marker	tendon of biceps brachii, stromal cell of endometrium, right coronary artery
TUBB1	140	tissue_specific	marker	monocyte, mononuclear cell, leukocyte
ACTN1	292	ubiquitous	marker	blood vessel layer, saphenous vein, ascending aorta
TRPM7	247	ubiquitous	marker	left ventricle myocardium, calcaneal tendon, cardiac muscle of right atrium
GFI1B	126	tissue_specific	marker	sperm, trabecular bone tissue, monocyte
GP1BA	186	tissue_specific	marker	monocyte, mononuclear cell, leukocyte
GP1BB	121	broad	marker	monocyte, leukocyte, granulocyte
ITGA2B	182	broad	marker	monocyte, mononuclear cell, leukocyte
ITGB3	199	ubiquitous	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 8.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TUBB1	4,106
ITGB3	3,274
ACTN1	3,220
ITGA2B	2,486
TRPM7	1,995
GP1BA	1,703
GFI1B	1,554
GP1BB	1,280
TPM4	557

Intra-cohort edges

A	B	Sources
ACTN1	GFI1B	intact
ACTN1	TPM4	biogrid_interaction
GFI1B	ITGA2B	string_interaction
GP1BA	GP1BB	biogrid_interaction, intact, string_interaction
GP1BA	ITGA2B	string_interaction
GP1BA	ITGB3	string_interaction
GP1BB	ITGA2B	string_interaction
ITGA2B	ITGB3	biogrid_interaction, intact, string_interaction

Structural data

PDB: 5 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ITGB3	P05106	123
ITGA2B	P08514	78
GP1BA	P07359	22
ACTN1	P12814	4
GP1BB	P13224	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TPM4	P67936	93.33
TUBB1	Q9H4B7	90.92
TRPM7	Q96QT4	69.90
GFI1B	Q5VTD9	64.09

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 155. Enrichment computed across 9 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Platelet Aggregation (Plug Formation)	4	219.6×	2e-07	GP1BA, GP1BB, ITGA2B, ITGB3
Defective F9 activation	2	475.8×	3e-04	GP1BA, GP1BB
Enhanced binding of GP1BA variant to VWF multimer:collagen	2	407.9×	3e-04	GP1BA, GP1BB
Defective binding of VWF variant to GPIb:IX:V	2	407.9×	3e-04	GP1BA, GP1BB
Response to elevated platelet cytosolic Ca2+	3	61.2×	4e-04	ACTN1, ITGA2B, ITGB3
FXIIa, PKa-dependent activation of coagulation pathway	2	285.5×	5e-04	GP1BA, GP1BB
GP1b-IX-V activation signalling	2	237.9×	6e-04	GP1BA, GP1BB
Fibrin formation	2	219.6×	6e-04	ITGA2B, ITGB3
L1CAM interactions	3	45.1×	6e-04	TUBB1, ITGA2B, ITGB3
Hemostasis	4	18.0×	6e-04	TUBB1, ACTN1, ITGA2B, ITGB3
p130Cas linkage to MAPK signaling for integrins	2	190.3×	6e-04	ITGA2B, ITGB3
Platelet activation, signaling and aggregation	3	39.6×	6e-04	ACTN1, ITGA2B, ITGB3
GRB2:SOS provides linkage to MAPK signaling for Integrins	2	178.4×	6e-04	ITGA2B, ITGB3
Platelet Adhesion to exposed collagen	2	167.9×	6e-04	GP1BA, GP1BB
Amplification and propagation of coagulation cascade	2	158.6×	7e-04	GP1BA, GP1BB
Platelet degranulation	3	32.9×	8e-04	ACTN1, ITGA2B, ITGB3
Signal transduction by L1	2	129.8×	9e-04	ITGA2B, ITGB3
Syndecan interactions	2	105.7×	0.001	ACTN1, ITGB3
Integrin signaling	2	105.7×	0.001	ITGA2B, ITGB3
Signaling by RAS mutants	2	105.7×	0.001	ITGA2B, ITGB3
Extracellular matrix organization	3	23.7×	0.002	ACTN1, ITGA2B, ITGB3
Signaling by high-kinase activity BRAF mutants	2	79.3×	0.002	ITGA2B, ITGB3
MAP2K and MAPK activation	2	71.4×	0.002	ITGA2B, ITGB3
Signaling by RAF1 mutants	2	69.6×	0.002	ITGA2B, ITGB3
Signaling by moderate kinase activity BRAF mutants	2	63.4×	0.002	ITGA2B, ITGB3
Paradoxical activation of RAF signaling by kinase inactive BRAF	2	63.4×	0.002	ITGA2B, ITGB3
Signaling downstream of RAS mutants	2	63.4×	0.002	ITGA2B, ITGB3
Oncogenic MAPK signaling	2	62.1×	0.002	ITGA2B, ITGB3
Regulation of clotting cascade	2	58.3×	0.003	GP1BA, GP1BB
Axon guidance	3	16.9×	0.003	TUBB1, ITGA2B, 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 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
platelet formation	3	234.1×	2e-05	TPM4, TUBB1, ACTN1
platelet activation	3	89.2×	2e-04	GP1BA, GP1BB, ITGB3
blood coagulation, intrinsic pathway	2	468.1×	3e-04	GP1BA, GP1BB
positive regulation of platelet activation	2	288.1×	5e-04	GP1BA, GP1BB
megakaryocyte development	2	156.0×	0.002	GP1BA, GP1BB
release of sequestered calcium ion into cytosol	2	76.4×	0.005	GP1BA, GP1BB
platelet aggregation	2	74.9×	0.005	TUBB1, ITGB3
regulation of serotonin uptake	1	1872.4×	0.007	ITGB3
positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathway	1	1872.4×	0.007	ITGB3
calcium-dependent cell-matrix adhesion	1	936.2×	0.009	TRPM7
negative regulation of lipoprotein metabolic process	1	936.2×	0.009	ITGB3
regulation of trophoblast cell migration	1	936.2×	0.009	ITGB3
platelet morphogenesis	1	624.1×	0.009	ACTN1
maintenance of postsynaptic specialization structure	1	624.1×	0.009	ITGB3
regulation of postsynaptic neurotransmitter receptor diffusion trapping	1	624.1×	0.009	ITGB3
blood coagulation	2	38.6×	0.009	GP1BA, ITGB3
cell-matrix adhesion	2	36.4×	0.009	ITGA2B, ITGB3
integrin-mediated signaling pathway	2	35.7×	0.009	ITGA2B, ITGB3
cell adhesion	3	12.5×	0.009	GP1BA, GP1BB, ITGB3
negative regulation of lipid transport	1	468.1×	0.011	ITGB3
tube development	1	468.1×	0.011	ITGB3
apolipoprotein A-I-mediated signaling pathway	1	468.1×	0.011	ITGB3
actin filament organization	2	26.4×	0.012	TPM4, ACTN1
cell-substrate junction assembly	1	312.1×	0.014	ITGB3
intracellular magnesium ion homeostasis	1	312.1×	0.014	TRPM7
positive regulation of glomerular mesangial cell proliferation	1	312.1×	0.014	ITGB3
magnesium ion homeostasis	1	208.1×	0.016	TRPM7
smooth muscle cell migration	1	208.1×	0.016	ITGB3
regulation of blood coagulation	1	208.1×	0.016	GP1BA
actin filament network formation	1	208.1×	0.016	ACTN1

Therapeutics

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 6

Druggability breadth: 7 of 9 evidence-associated genes (78%) 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
TUBB1	COLCHICINE
ITGA2B	EPTIFIBATIDE
ITGB3	EPTIFIBATIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TUBB1	22	4
ITGB3	18	4
ITGA2B	14	4
TPM4	0	0
ACTN1	0	0
TRPM7	0	0
GFI1B	0	0
GP1BA	0	0
GP1BB	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COLCHICINE	4	TUBB1
VINBLASTINE	4	TUBB1
LEVOFLOXACIN ANHYDROUS	4	TUBB1
DOCETAXEL	4	TUBB1
NOSCAPINE	4	TUBB1
VINBLASTINE SULFATE	4	TUBB1
PACLITAXEL	4	ITGB3, TUBB1
LEVOFLOXACIN	4	TUBB1
VINORELBINE	4	TUBB1
TIRBANIBULIN	4	TUBB1
PODOFILOX	4	TUBB1
VINCRISTINE	4	TUBB1
DOCETAXEL ANHYDROUS	4	TUBB1
EPTIFIBATIDE	4	ITGA2B, ITGB3
ASPIRIN	4	ITGA2B, ITGB3
TIROFIBAN	4	ITGA2B, ITGB3
PATUPILONE	3	TUBB1
NAFAMOSTAT	3	ITGA2B, ITGB3
CILENGITIDE	3	ITGA2B, ITGB3
TALTOBULIN	2	TUBB1
ABT-751	2	TUBB1
MAYTANSINE	2	TUBB1
DOLASTATIN-10	2	TUBB1
INDIBULIN	2	TUBB1
PARBENDAZOLE	2	TUBB1
NOCODAZOLE	2	TUBB1
LAMIFIBAN	2	ITGA2B, ITGB3
ROXIFIBAN	2	ITGA2B, ITGB3
FRADAFIBAN	2	ITGA2B, ITGB3
LOTRAFIBAN	2	ITGA2B, ITGB3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TUBB1	1,765	Binding:1723, Functional:36, ADMET:6
ITGB3	771	Binding:575, Functional:183, ADMET:13
ITGA2B	407	Binding:246, Functional:159, ADMET:2
TRPM7	34	Binding:34
TPM4	4	Binding:4
ACTN1	1	Binding:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TUBB1	1,765
ITGA2B	407
ITGB3	771

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; 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)
COLCHICINE	4	TUBB1
VINBLASTINE	4	TUBB1
LEVOFLOXACIN ANHYDROUS	4	TUBB1
DOCETAXEL	4	TUBB1
NOSCAPINE	4	TUBB1
VINBLASTINE SULFATE	4	TUBB1
PACLITAXEL	4	ITGB3, TUBB1
LEVOFLOXACIN	4	TUBB1
VINORELBINE	4	TUBB1
TIRBANIBULIN	4	TUBB1
PODOFILOX	4	TUBB1
VINCRISTINE	4	TUBB1
DOCETAXEL ANHYDROUS	4	TUBB1
EPTIFIBATIDE	4	ITGA2B, ITGB3
ASPIRIN	4	ITGA2B, ITGB3
TIROFIBAN	4	ITGA2B, ITGB3
PATUPILONE	3	TUBB1
NAFAMOSTAT	3	ITGA2B, ITGB3
CILENGITIDE	3	ITGA2B, ITGB3
TALTOBULIN	2	TUBB1
ABT-751	2	TUBB1
MAYTANSINE	2	TUBB1
DOLASTATIN-10	2	TUBB1
INDIBULIN	2	TUBB1
PARBENDAZOLE	2	TUBB1
NOCODAZOLE	2	TUBB1
LAMIFIBAN	2	ITGA2B, ITGB3
ROXIFIBAN	2	ITGA2B, ITGB3
FRADAFIBAN	2	ITGA2B, ITGB3
LOTRAFIBAN	2	ITGA2B, ITGB3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	TUBB1, ITGA2B, ITGB3
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	TRPM7
E	Difficult family or no structure, no drug	5	TPM4, ACTN1, GFI1B, GP1BA, GP1BB

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TPM4	4	—
ACTN1	1	—
TRPM7	34	—
GFI1B	0	—
GP1BA	0	—
GP1BB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.