Bleeding disorder, platelet-type, 24

Summary

Bleeding disorder, platelet-type, 24 (MONDO:0030996) is a disease caused by ITGB3 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: ITGB3 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 41

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	bleeding disorder, platelet-type, 24
Mondo ID	MONDO:0030996
OMIM	619271
UMLS	C5543280
MedGen	1785711
GARD	0018273
Is cancer (heuristic)	no

Also known as: BDPLT24 · bleeding disorder, platelet-type, 24 · bleeding disorder, platelet-type, 24, autosomal dominant · Glanzmann Thrombasthenia-Like With Macrothrombocytopenia 2

Data availability: 41 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › hemorrhagic disease › inherited bleeding disorder, platelet-type › bleeding disorder, platelet-type, 24

Related subtypes (27): gray platelet syndrome, primary release disorder of platelets, platelet-type von Willebrand disease, platelet-type bleeding disorder 16, platelet-type bleeding disorder 17, Ehlers-Danlos syndrome, fibronectinemic type, Bernard-Soulier syndrome, Scott syndrome, congenital thrombotic thrombocytopenic purpura, Quebec platelet disorder, platelet-type bleeding disorder 12, platelet-type bleeding disorder 10, platelet-type bleeding disorder 8, platelet-type bleeding disorder 14, platelet-type bleeding disorder 9, platelet-type bleeding disorder 11, platelet-type bleeding disorder 15, platelet-type bleeding disorder 18, platelet-type bleeding disorder 19, platelet-type bleeding disorder 20, macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder, bleeding disorder, platelet-type, 22, bleeding disorder, platelet-type, 21, Glanzmann thrombasthenia, bleeding diathesis due to thromboxane synthesis deficiency, bleeding disorder, platelet-type, 25

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

41 retrieved; paginated sample, class counts are floors:

16 uncertain significance, 15 pathogenic, 9 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
13564	NM_000212.3(ITGB3):c.2248C>T (p.Arg750Ter)	EFCAB13-DT	Pathogenic	reviewed by expert panel
1697255	NM_000212.3(ITGB3):c.2278C>T (p.Arg760Cys)	EFCAB13-DT	Pathogenic	criteria provided, single submitter
50227	NM_000212.3(ITGB3):c.2245G>C (p.Asp749His)	EFCAB13-DT	Pathogenic	no assertion criteria provided
13553	NM_000212.3(ITGB3):c.719G>A (p.Arg240Gln)	ITGB3	Pathogenic	reviewed by expert panel
13567	NM_000212.3(ITGB3):c.428T>G (p.Leu143Trp)	ITGB3	Pathogenic	reviewed by expert panel
1693575	NM_000212.3(ITGB3):c.1036-2A>G	ITGB3	Pathogenic	no assertion criteria provided
1879043	NM_000212.3(ITGB3):c.725G>A (p.Arg242Gln)	ITGB3	Pathogenic	reviewed by expert panel
50228	NM_000212.3(ITGB3):c.2134+1G>C	ITGB3	Pathogenic	criteria provided, single submitter
812736	NM_000212.3(ITGB3):c.565C>T (p.Pro189Ser)	ITGB3	Pathogenic	reviewed by expert panel
953028	NM_000212.3(ITGB3):c.31T>C (p.Trp11Arg)	ITGB3	Pathogenic	reviewed by expert panel
953050	NM_000212.3(ITGB3):c.79+1G>A	ITGB3	Pathogenic	reviewed by expert panel
996178	NM_000212.3(ITGB3):c.709_710del (p.Ser237fs)	ITGB3	Pathogenic	reviewed by expert panel
996188	NM_000212.3(ITGB3):c.431T>G (p.Met144Arg)	ITGB3	Pathogenic	reviewed by expert panel
996193	NM_000212.3(ITGB3):c.100C>T (p.Arg34Ter)	ITGB3	Pathogenic	reviewed by expert panel
850886	NM_000212.3(ITGB3):c.777+1G>A	LOC130061044	Pathogenic	reviewed by expert panel
1199410	NM_000212.3(ITGB3):c.1132C>T (p.Arg378Cys)	ITGB3	Likely pathogenic	criteria provided, single submitter
1210200	NM_000212.3(ITGB3):c.1031A>C (p.Tyr344Ser)	ITGB3	Likely pathogenic	reviewed by expert panel
1879042	NM_000212.3(ITGB3):c.1813G>A (p.Gly605Ser)	ITGB3	Likely pathogenic	reviewed by expert panel
2889941	NM_000212.3(ITGB3):c.939+1G>T	ITGB3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3242406	NM_000212.3(ITGB3):c.563C>T (p.Ser188Leu)	ITGB3	Likely pathogenic	reviewed by expert panel
4277409	NM_000212.3(ITGB3):c.939+5_939+35del	ITGB3	Likely pathogenic	criteria provided, single submitter
953041	NM_000212.3(ITGB3):c.1913+5G>T	ITGB3	Likely pathogenic	reviewed by expert panel
953053	NM_000212.3(ITGB3):c.448A>G (p.Met150Val)	ITGB3	Likely pathogenic	reviewed by expert panel
996166	NM_000212.3(ITGB3):c.353T>A (p.Leu118His)	ITGB3	Likely pathogenic	reviewed by expert panel
2408588	NM_000212.3(ITGB3):c.2279G>A (p.Arg760His)	EFCAB13-DT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1693574	NM_000212.3(ITGB3):c.2209G>A (p.Ala737Thr)	EFCAB13-DT	Uncertain significance	criteria provided, single submitter
1697253	NM_000212.3(ITGB3):c.2236A>C (p.Thr746Pro)	EFCAB13-DT	Uncertain significance	no assertion criteria provided
1697254	NM_000212.3(ITGB3):c.2243A>C (p.His748Pro)	EFCAB13-DT	Uncertain significance	no assertion criteria provided
3582202	NM_000212.3(ITGB3):c.2351C>T (p.Thr784Met)	EFCAB13-DT	Uncertain significance	criteria provided, multiple submitters, no conflicts
50229	NM_000212.3(ITGB3):c.2231T>C (p.Leu744Pro)	EFCAB13-DT	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 3 · 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
ITGB3	Strong	Autosomal dominant	bleeding disorder, platelet-type, 24	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ITGB3	Orphanet:140957	Autosomal dominant macrothrombocytopenia
ITGB3	Orphanet:849	Glanzmann thrombasthenia
ITGB3	Orphanet:853	Fetal and neonatal alloimmune thrombocytopenia

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ITGB3	HGNC:6156	ENSG00000259207	P05106	Integrin beta-3	gencc,clinvar
EFCAB13-DT	HGNC:55338	ENSG00000263293		EFCAB13 divergent transcript	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ITGB3	Other/Unknown	no		Integrin_bsu_VWA, Integrin_bsu_tail, EGF_extracell
EFCAB13-DT	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
leukocyte	1
monocyte	1
mononuclear cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
right lobe of thyroid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ITGB3	199	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
EFCAB13-DT	155	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, right lobe of thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITGB3	3,274
EFCAB13-DT	0

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ITGB3	P05106	123

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 49. Enrichment computed across 2 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
PECAM1 interactions	1	878.5×	0.009	ITGB3
Fibrin formation	1	878.5×	0.009	ITGB3
p130Cas linkage to MAPK signaling for integrins	1	761.3×	0.009	ITGB3
GRB2:SOS provides linkage to MAPK signaling for Integrins	1	713.8×	0.009	ITGB3
Mechanical load activates signaling by PIEZO1 and integrins in osteocytes	1	671.8×	0.009	ITGB3
Signal transduction by L1	1	519.1×	0.009	ITGB3
Platelet Aggregation (Plug Formation)	1	439.2×	0.009	ITGB3
Syndecan interactions	1	423.0×	0.009	ITGB3
Integrin signaling	1	423.0×	0.009	ITGB3
Signaling by RAS mutants	1	423.0×	0.009	ITGB3
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	1	356.9×	0.009	ITGB3
Elastic fibre formation	1	335.9×	0.009	ITGB3
TGF-beta receptor signaling activates SMADs	1	326.3×	0.009	ITGB3
Signaling by high-kinase activity BRAF mutants	1	317.2×	0.009	ITGB3
Molecules associated with elastic fibres	1	308.6×	0.009	ITGB3
Response of endothelial cells to shear stress	1	300.5×	0.009	ITGB3
MAP2K and MAPK activation	1	285.5×	0.009	ITGB3
Signaling by RAF1 mutants	1	278.5×	0.009	ITGB3
Cellular responses to mechanical stimuli	1	259.6×	0.009	ITGB3
Signaling by moderate kinase activity BRAF mutants	1	253.8×	0.009	ITGB3
Paradoxical activation of RAF signaling by kinase inactive BRAF	1	253.8×	0.009	ITGB3
Signaling downstream of RAS mutants	1	253.8×	0.009	ITGB3
Oncogenic MAPK signaling	1	248.3×	0.009	ITGB3
Signaling by VEGF	1	219.6×	0.009	ITGB3
Signaling by TGF-beta Receptor Complex	1	200.3×	0.010	ITGB3
Signaling by BRAF and RAF1 fusions	1	170.4×	0.011	ITGB3
Response to elevated platelet cytosolic Ca2+	1	163.1×	0.011	ITGB3
Non-integrin membrane-ECM interactions	1	154.3×	0.011	ITGB3
ECM proteoglycans	1	150.3×	0.011	ITGB3
VEGFA-VEGFR2 Pathway	1	139.3×	0.012	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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of serotonin uptake	1	16852.0×	0.002	ITGB3
positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathway	1	16852.0×	0.002	ITGB3
negative regulation of lipoprotein metabolic process	1	8426.0×	0.002	ITGB3
regulation of trophoblast cell migration	1	8426.0×	0.002	ITGB3
maintenance of postsynaptic specialization structure	1	5617.3×	0.002	ITGB3
regulation of postsynaptic neurotransmitter receptor diffusion trapping	1	5617.3×	0.002	ITGB3
negative regulation of lipid transport	1	4213.0×	0.002	ITGB3
tube development	1	4213.0×	0.002	ITGB3
apolipoprotein A-I-mediated signaling pathway	1	4213.0×	0.002	ITGB3
cell-substrate junction assembly	1	2808.7×	0.002	ITGB3
positive regulation of glomerular mesangial cell proliferation	1	2808.7×	0.002	ITGB3
smooth muscle cell migration	1	1872.4×	0.002	ITGB3
regulation of extracellular matrix organization	1	1872.4×	0.002	ITGB3
angiogenesis involved in wound healing	1	1685.2×	0.002	ITGB3
blood coagulation, fibrin clot formation	1	1685.2×	0.002	ITGB3
negative regulation of lipid storage	1	1532.0×	0.002	ITGB3
negative regulation of low-density lipoprotein particle clearance	1	1532.0×	0.002	ITGB3
regulation of bone resorption	1	1532.0×	0.002	ITGB3
mesodermal cell differentiation	1	1532.0×	0.002	ITGB3
negative regulation of macrophage derived foam cell differentiation	1	1296.3×	0.002	ITGB3
cellular response to insulin-like growth factor stimulus	1	1296.3×	0.002	ITGB3
positive regulation of osteoblast proliferation	1	1203.7×	0.002	ITGB3
positive regulation of fibroblast migration	1	1123.5×	0.002	ITGB3
positive regulation of vascular endothelial growth factor signaling pathway	1	1123.5×	0.002	ITGB3
positive regulation of vascular endothelial growth factor receptor signaling pathway	1	1053.2×	0.002	ITGB3
positive regulation of cell adhesion mediated by integrin	1	1053.2×	0.002	ITGB3
wound healing, spreading of epidermal cells	1	1053.2×	0.002	ITGB3
positive regulation of smooth muscle cell migration	1	991.3×	0.002	ITGB3
positive regulation of bone resorption	1	991.3×	0.002	ITGB3
regulation of release of sequestered calcium ion into cytosol	1	936.2×	0.002	ITGB3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
ITGB3	EPTIFIBATIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ITGB3	18	4
EFCAB13-DT	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
EPTIFIBATIDE	4	ITGB3
PACLITAXEL	4	ITGB3
TIROFIBAN	4	ITGB3
ASPIRIN	4	ITGB3
CILENGITIDE	3	ITGB3
NAFAMOSTAT	3	ITGB3
LAMIFIBAN	2	ITGB3
ROXIFIBAN	2	ITGB3
FRADAFIBAN	2	ITGB3
LOTRAFIBAN	2	ITGB3
SIBRAFIBAN	2	ITGB3
ORBOFIBAN	2	ITGB3
XEMILOFIBAN	2	ITGB3
GANTOFIBAN	2	ITGB3
ELAROFIBAN	2	ITGB3
GLPG-0187	1	ITGB3
GSK-3008348 FREE BASE	1	ITGB3
GSK-3008348	1	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
ITGB3	771	Binding:575, Functional:183, ADMET:13

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ITGB3	771

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

18 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)
EPTIFIBATIDE	4	ITGB3
PACLITAXEL	4	ITGB3
TIROFIBAN	4	ITGB3
ASPIRIN	4	ITGB3
CILENGITIDE	3	ITGB3
NAFAMOSTAT	3	ITGB3
LAMIFIBAN	2	ITGB3
ROXIFIBAN	2	ITGB3
FRADAFIBAN	2	ITGB3
LOTRAFIBAN	2	ITGB3
SIBRAFIBAN	2	ITGB3
ORBOFIBAN	2	ITGB3
XEMILOFIBAN	2	ITGB3
GANTOFIBAN	2	ITGB3
ELAROFIBAN	2	ITGB3
GLPG-0187	1	ITGB3
GSK-3008348 FREE BASE	1	ITGB3
GSK-3008348	1	ITGB3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ITGB3
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	EFCAB13-DT

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
EFCAB13-DT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.