Platelet-type bleeding disorder 16

Summary

Platelet-type bleeding disorder 16 (MONDO:0008552) is a disease caused by variants in ITGA2B and ITGB3, with 3 cohort genes.

At a glance

• Causal genes: ITGA2B (GenCC Strong), ITGB3 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 55

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	platelet-type bleeding disorder 16
Mondo ID	MONDO:0008552
MeSH	C566061
OMIM	187800
DOID	DOID:0060691
UMLS	C5442010
MedGen	1781222
GARD	0024629
Is cancer (heuristic)	no

Also known as: BDPLT16 · bleeding disorder, platelet-type, 16 · bleeding disorder, platelet-type, 16, autosomal dominant · platelet-type bleeding disorder 16

Data availability: 55 ClinVar variants · 5 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 › platelet-type bleeding disorder 16

Related subtypes (27): gray platelet syndrome, primary release disorder of platelets, platelet-type von Willebrand disease, 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, 24, 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

55 retrieved; paginated sample, class counts are floors:

27 uncertain significance, 11 pathogenic, 7 likely pathogenic, 4 benign, 3 conflicting classifications of pathogenicity, 2 likely benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
13564	NM_000212.3(ITGB3):c.2248C>T (p.Arg750Ter)	EFCAB13-DT	Pathogenic	reviewed by expert panel
1803116	NM_000419.5(ITGA2B):c.1545-1G>A	ITGA2B	Pathogenic	reviewed by expert panel
225393	NM_000419.5(ITGA2B):c.2333A>C (p.Gln778Pro)	ITGA2B	Pathogenic	reviewed by expert panel
2892	NM_000419.5(ITGA2B):c.1750C>T (p.Arg584Ter)	ITGA2B	Pathogenic	reviewed by expert panel
2901	NM_000419.5(ITGA2B):c.641T>C (p.Leu214Pro)	ITGA2B	Pathogenic	reviewed by expert panel
627020	NM_000419.5(ITGA2B):c.1772A>C (p.Asp591Ala)	ITGA2B	Pathogenic	reviewed by expert panel
953019	NM_000419.5(ITGA2B):c.2929C>T (p.Arg977Ter)	ITGA2B	Pathogenic	reviewed by expert panel
953034	NM_000419.5(ITGA2B):c.291del (p.Ser98fs)	ITGA2B	Pathogenic	reviewed by expert panel
13553	NM_000212.3(ITGB3):c.719G>A (p.Arg240Gln)	ITGB3	Pathogenic	reviewed by expert panel
374015	NM_000212.3(ITGB3):c.1699C>T (p.Gln567Ter)	ITGB3	Pathogenic	reviewed by expert panel
996178	NM_000212.3(ITGB3):c.709_710del (p.Ser237fs)	ITGB3	Pathogenic	reviewed by expert panel
1691488	NM_000419.5(ITGA2B):c.3092del (p.Leu1031fs)	ITGA2B	Likely pathogenic	reviewed by expert panel
3582140	NM_000419.5(ITGA2B):c.2935G>T (p.Glu979Ter)	ITGA2B	Likely pathogenic	criteria provided, single submitter
3582142	NM_000419.5(ITGA2B):c.879G>A (p.Trp293Ter)	ITGA2B	Likely pathogenic	criteria provided, single submitter
3582143	NM_000419.5(ITGA2B):c.517G>T (p.Glu173Ter)	ITGA2B	Likely pathogenic	criteria provided, single submitter
3891410	NM_000419.5(ITGA2B):c.797G>A (p.Trp266Ter)	ITGA2B	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4294453	NM_000419.5(ITGA2B):c.703_704del (p.Phe235fs)	ITGA2B	Likely pathogenic	criteria provided, single submitter
374016	NM_000212.3(ITGB3):c.749A>G (p.Asp250Gly)	ITGB3	Likely pathogenic	reviewed by expert panel
2572659	NM_000419.5(ITGA2B):c.3070T>A (p.Phe1024Ile)	ITGA2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3582141	NM_000419.5(ITGA2B):c.2841+13G>A	ITGA2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
695309	NM_000419.5(ITGA2B):c.2602G>A (p.Val868Met)	ITGA2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030779	NM_000419.5(ITGA2B):c.1142C>T (p.Thr381Ile)	ITGA2B	Uncertain significance	reviewed by expert panel
1030780	NM_000419.5(ITGA2B):c.1752+5G>A	ITGA2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1339143	NM_000419.5(ITGA2B):c.590A>G (p.Tyr197Cys)	ITGA2B	Uncertain significance	criteria provided, single submitter
1684323	NM_000419.5(ITGA2B):c.1879-14A>G	ITGA2B	Uncertain significance	criteria provided, single submitter
1695976	NM_000419.5(ITGA2B):c.2982del (p.Ile995fs)	ITGA2B	Uncertain significance	no assertion criteria provided
1697247	NM_000419.5(ITGA2B):c.580G>A (p.Asp194Asn)	ITGA2B	Uncertain significance	no assertion criteria provided
1697249	NM_000419.5(ITGA2B):c.176A>G (p.Asp59Gly)	ITGA2B	Uncertain significance	no assertion criteria provided
1697251	NM_000419.5(ITGA2B):c.3020G>T (p.Gly1007Val)	ITGA2B	Uncertain significance	no assertion criteria provided
1698808	NM_000419.5(ITGA2B):c.2198C>T (p.Ala733Val)	ITGA2B	Uncertain significance	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · Orphanet: 6 · 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
ITGA2B	Strong	Autosomal dominant	platelet-type bleeding disorder 16	10
ITGB3	Strong	Autosomal dominant	bleeding disorder, platelet-type, 24	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ITGA2B	HGNC:6138	ENSG00000005961	P08514	Integrin alpha-IIb	gencc,clinvar
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)
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: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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	9.7×	0.199
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ITGA2B	Antibody/Immunoglobulin	yes		Integrin_alpha, FG-GAP, Int_alpha_beta-p
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.

2 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
leukocyte	2
monocyte	2
mononuclear cell	2
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
ITGA2B	182	broad	marker	monocyte, mononuclear cell, leukocyte
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: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITGB3	3,274
ITGA2B	2,486
EFCAB13-DT	0

Intra-cohort edges

A	B	Sources
ITGA2B	ITGB3	biogrid_interaction, intact, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ITGB3	P05106	123
ITGA2B	P08514	78

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 54. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Fibrin formation	2	878.5×	3e-05	ITGA2B, ITGB3
p130Cas linkage to MAPK signaling for integrins	2	761.3×	3e-05	ITGA2B, ITGB3
GRB2:SOS provides linkage to MAPK signaling for Integrins	2	713.8×	3e-05	ITGA2B, ITGB3
Signal transduction by L1	2	519.1×	4e-05	ITGA2B, ITGB3
Platelet Aggregation (Plug Formation)	2	439.2×	4e-05	ITGA2B, ITGB3
Integrin signaling	2	423.0×	4e-05	ITGA2B, ITGB3
Signaling by RAS mutants	2	423.0×	4e-05	ITGA2B, ITGB3
Signaling by high-kinase activity BRAF mutants	2	317.2×	6e-05	ITGA2B, ITGB3
MAP2K and MAPK activation	2	285.5×	6e-05	ITGA2B, ITGB3
Signaling by RAF1 mutants	2	278.5×	6e-05	ITGA2B, ITGB3
Signaling by moderate kinase activity BRAF mutants	2	253.8×	6e-05	ITGA2B, ITGB3
Paradoxical activation of RAF signaling by kinase inactive BRAF	2	253.8×	6e-05	ITGA2B, ITGB3
Signaling downstream of RAS mutants	2	253.8×	6e-05	ITGA2B, ITGB3
Oncogenic MAPK signaling	2	248.3×	6e-05	ITGA2B, ITGB3
Signaling by BRAF and RAF1 fusions	2	170.4×	1e-04	ITGA2B, ITGB3
Response to elevated platelet cytosolic Ca2+	2	163.1×	1e-04	ITGA2B, ITGB3
ECM proteoglycans	2	150.3×	1e-04	ITGA2B, ITGB3
Integrin cell surface interactions	2	134.3×	2e-04	ITGA2B, ITGB3
MAPK1/MAPK3 signaling	2	131.3×	2e-04	ITGA2B, ITGB3
L1CAM interactions	2	120.2×	2e-04	ITGA2B, ITGB3
Platelet activation, signaling and aggregation	2	105.7×	2e-04	ITGA2B, ITGB3
MAPK family signaling cascades	2	102.9×	2e-04	ITGA2B, ITGB3
Platelet degranulation	2	87.8×	3e-04	ITGA2B, ITGB3
Extracellular matrix organization	2	63.1×	6e-04	ITGA2B, ITGB3
RAF/MAP kinase cascade	2	61.1×	6e-04	ITGA2B, ITGB3
Diseases of signal transduction by growth factor receptors and second messengers	2	56.8×	6e-04	ITGA2B, ITGB3
Axon guidance	2	45.1×	1e-03	ITGA2B, ITGB3
Nervous system development	2	42.9×	0.001	ITGA2B, ITGB3
Hemostasis	2	36.0×	0.001	ITGA2B, ITGB3
PECAM1 interactions	1	439.2×	0.004	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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cell-matrix adhesion	2	163.6×	0.001	ITGA2B, ITGB3
integrin-mediated signaling pathway	2	160.5×	0.001	ITGA2B, ITGB3
regulation of serotonin uptake	1	8426.0×	0.002	ITGB3
positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathway	1	8426.0×	0.002	ITGB3
negative regulation of lipoprotein metabolic process	1	4213.0×	0.003	ITGB3
regulation of trophoblast cell migration	1	4213.0×	0.003	ITGB3
maintenance of postsynaptic specialization structure	1	2808.7×	0.003	ITGB3
regulation of postsynaptic neurotransmitter receptor diffusion trapping	1	2808.7×	0.003	ITGB3
negative regulation of lipid transport	1	2106.5×	0.003	ITGB3
tube development	1	2106.5×	0.003	ITGB3
apolipoprotein A-I-mediated signaling pathway	1	2106.5×	0.003	ITGB3
cell-substrate junction assembly	1	1404.3×	0.004	ITGB3
positive regulation of glomerular mesangial cell proliferation	1	1404.3×	0.004	ITGB3
smooth muscle cell migration	1	936.2×	0.004	ITGB3
regulation of extracellular matrix organization	1	936.2×	0.004	ITGB3
angiogenesis involved in wound healing	1	842.6×	0.004	ITGB3
blood coagulation, fibrin clot formation	1	842.6×	0.004	ITGB3
negative regulation of lipid storage	1	766.0×	0.004	ITGB3
negative regulation of low-density lipoprotein particle clearance	1	766.0×	0.004	ITGB3
regulation of bone resorption	1	766.0×	0.004	ITGB3
mesodermal cell differentiation	1	766.0×	0.004	ITGB3
negative regulation of macrophage derived foam cell differentiation	1	648.1×	0.004	ITGB3
cellular response to insulin-like growth factor stimulus	1	648.1×	0.004	ITGB3
positive regulation of osteoblast proliferation	1	601.9×	0.004	ITGB3
positive regulation of fibroblast migration	1	561.7×	0.004	ITGB3
positive regulation of vascular endothelial growth factor signaling pathway	1	561.7×	0.004	ITGB3
positive regulation of vascular endothelial growth factor receptor signaling pathway	1	526.6×	0.004	ITGB3
positive regulation of cell adhesion mediated by integrin	1	526.6×	0.004	ITGB3
wound healing, spreading of epidermal cells	1	526.6×	0.004	ITGB3
positive regulation of leukocyte migration	1	495.6×	0.004	ITGA2B

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 1

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
ITGA2B	EPTIFIBATIDE
ITGB3	EPTIFIBATIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ITGB3	18	4
ITGA2B	14	4
EFCAB13-DT	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
EPTIFIBATIDE	4	ITGA2B, ITGB3
ASPIRIN	4	ITGA2B, ITGB3
TIROFIBAN	4	ITGA2B, ITGB3
PACLITAXEL	4	ITGB3
NAFAMOSTAT	3	ITGA2B, ITGB3
CILENGITIDE	3	ITGA2B, ITGB3
LAMIFIBAN	2	ITGA2B, ITGB3
ROXIFIBAN	2	ITGA2B, ITGB3
FRADAFIBAN	2	ITGA2B, ITGB3
LOTRAFIBAN	2	ITGA2B, ITGB3
SIBRAFIBAN	2	ITGA2B, ITGB3
ORBOFIBAN	2	ITGA2B, ITGB3
XEMILOFIBAN	2	ITGA2B, ITGB3
GANTOFIBAN	2	ITGA2B, ITGB3
ELAROFIBAN	2	ITGA2B, 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
ITGA2B	407	Binding:246, Functional:159, ADMET:2

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ITGA2B	407
ITGB3	771

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	ITGA2B, ITGB3
ASPIRIN	4	ITGA2B, ITGB3
TIROFIBAN	4	ITGA2B, ITGB3
PACLITAXEL	4	ITGB3
NAFAMOSTAT	3	ITGA2B, ITGB3
CILENGITIDE	3	ITGA2B, ITGB3
LAMIFIBAN	2	ITGA2B, ITGB3
ROXIFIBAN	2	ITGA2B, ITGB3
FRADAFIBAN	2	ITGA2B, ITGB3
LOTRAFIBAN	2	ITGA2B, ITGB3
SIBRAFIBAN	2	ITGA2B, ITGB3
ORBOFIBAN	2	ITGA2B, ITGB3
XEMILOFIBAN	2	ITGA2B, ITGB3
GANTOFIBAN	2	ITGA2B, ITGB3
ELAROFIBAN	2	ITGA2B, 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)	2	ITGA2B, 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.