Glanzmann thrombasthenia 1

Summary

Glanzmann thrombasthenia 1 (MONDO:0031332) is a disease caused by ITGA2B (GenCC Strong), with 3 cohort genes and 15 clinical trials. Top therapeutic interventions include alefacept, concizumab, and fludarabine phosphate.

At a glance

• Causal gene: ITGA2B (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 110
• Clinical trials: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Glanzmann thrombasthenia 1
Mondo ID	MONDO:0031332
MeSH	D013915
OMIM	273800
DOID	DOID:2219
NCIT	C61249
SNOMED CT	32942005
GARD	0015240
Is cancer (heuristic)	no

Also known as: BDPLT2 · deficiency of GP 2B 3A complex · Diacyclothrombopathia 2B 3A · Glanzmann thrombasthenia · Glanzmann thrombasthenia 1 · Glanzmann thrombasthenia type A · Glanzmann’s thrombasthenia · GT · Platelet glycoprotein 2B 3A deficiency · platelet glycoprotein IIb-IIIa deficiency · thrombasthenia · thrombasthenia of Glanzmann and Naegeli

Data availability: 110 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 › Glanzmann thrombasthenia › Glanzmann thrombasthenia 1

Related subtypes (1): Glanzmann thrombasthenia 2

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

110 retrieved; paginated sample, class counts are floors:

41 pathogenic, 30 uncertain significance, 28 likely pathogenic, 6 benign, 3 conflicting classifications of pathogenicity, 2 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
1684324	NM_000419.5(ITGA2B):c.138dup (p.Gly47fs)	ITGA2B	Pathogenic	reviewed by expert panel
1687215	NM_000419.5(ITGA2B):c.21_22del (p.Leu8fs)	ITGA2B	Pathogenic	criteria provided, single submitter
1703867	NM_000419.5(ITGA2B):c.337C>T (p.Gln113Ter)	ITGA2B	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
2889	NM_000419.5(ITGA2B):c.409-2_419del	ITGA2B	Pathogenic	reviewed by expert panel
2890	NM_000419.5(ITGA2B):c.188+484_892-70delinsCAATCCCACA	ITGA2B	Pathogenic	no assertion criteria provided
2892	NM_000419.5(ITGA2B):c.1750C>T (p.Arg584Ter)	ITGA2B	Pathogenic	reviewed by expert panel
2895	NM_000419.5(ITGA2B):c.1544+1G>A	ITGA2B	Pathogenic	reviewed by expert panel
2896	NM_000419.5(ITGA2B):c.1073G>A (p.Arg358His)	ITGA2B	Pathogenic	reviewed by expert panel
2899	NM_000419.5(ITGA2B):c.1063G>A (p.Glu355Lys)	ITGA2B	Pathogenic	reviewed by expert panel
2900	NM_000419.5(ITGA2B):c.1787T>C (p.Ile596Thr)	ITGA2B	Pathogenic	reviewed by expert panel
2901	NM_000419.5(ITGA2B):c.641T>C (p.Leu214Pro)	ITGA2B	Pathogenic	reviewed by expert panel
2903	NM_000419.5(ITGA2B):c.1878G>C (p.Gln626His)	ITGA2B	Pathogenic	reviewed by expert panel
3069204	NM_000419.5(ITGA2B):c.670G>A (p.Gly224Ser)	ITGA2B	Pathogenic	criteria provided, single submitter
381747	NM_000419.5(ITGA2B):c.2944G>A (p.Val982Met)	ITGA2B	Pathogenic	reviewed by expert panel
381748	NM_000419.5(ITGA2B):c.1234G>A (p.Gly412Arg)	ITGA2B	Pathogenic	reviewed by expert panel
4531657	NM_000419.5(ITGA2B):c.2678del (p.Phe893fs)	ITGA2B	Pathogenic	criteria provided, single submitter
627020	NM_000419.5(ITGA2B):c.1772A>C (p.Asp591Ala)	ITGA2B	Pathogenic	reviewed by expert panel
627093	NM_000419.5(ITGA2B):c.559del (p.Val187fs)	ITGA2B	Pathogenic	reviewed by expert panel
627296	NM_000419.5(ITGA2B):c.3060+2T>C	ITGA2B	Pathogenic	reviewed by expert panel
953000	NM_000419.5(ITGA2B):c.526C>G (p.Pro176Ala)	ITGA2B	Pathogenic	reviewed by expert panel
953002	NM_000419.5(ITGA2B):c.1440-13_1440-1del	ITGA2B	Pathogenic	reviewed by expert panel
953004	NM_000419.5(ITGA2B):c.1214T>C (p.Ile405Thr)	ITGA2B	Pathogenic	reviewed by expert panel
953033	NM_000419.5(ITGA2B):c.1882C>T (p.Arg628Ter)	ITGA2B	Pathogenic	reviewed by expert panel
953034	NM_000419.5(ITGA2B):c.291del (p.Ser98fs)	ITGA2B	Pathogenic	reviewed by expert panel
953037	NM_000419.5(ITGA2B):c.257T>C (p.Leu86Pro)	ITGA2B	Pathogenic	reviewed by expert panel
953055	NM_000419.5(ITGA2B):c.1612G>T (p.Glu538Ter)	ITGA2B	Pathogenic	reviewed by expert panel
953057	NM_000419.5(ITGA2B):c.2965del (p.Ala989fs)	ITGA2B	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · 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	Definitive	Autosomal recessive	Glanzmann’s thrombasthenia	10

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
EFCAB13-DT	HGNC:55338	ENSG00000263293		EFCAB13 divergent transcript	clinvar
ITGB3	HGNC:6156	ENSG00000259207	P05106	Integrin beta-3	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
EFCAB13-DT	Other/Unknown	no
ITGB3	Other/Unknown	no		Integrin_bsu_VWA, Integrin_bsu_tail, EGF_extracell

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
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
ITGB3	199	ubiquitous	marker	monocyte, mononuclear cell, leukocyte

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

Drugs indicated for this disease

1 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Eptacog Alfa (Activated)	Approved (phase 4)

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: 15.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	10
PHASE2	2
PHASE1/PHASE2	2
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06211634	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Phase 1/2 Study to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of HMB-001 in Glanzmann Thrombasthenia
NCT07136857	PHASE2	RECRUITING	Eptacog Beta in Glanzmann’s (HeT_LFB-Strength-Study_FID531)
NCT03333486	PHASE2	TERMINATED	Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer
NCT04548791	PHASE1/PHASE2	TERMINATED	Study of Coagulation Factor VIIa Marzeptacog Alfa (Activated) in Subjects With Inherited Bleeding Disorders
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT00230165	Not specified	RECRUITING	The Genetics and Functional Basis of Inherited Platelet, White Blood Cell, Red Blood Cell, and Blood Clotting Disorders.
NCT04119908	Not specified	RECRUITING	Videomicroscopy for the Prediction of Bleeding in Constitutional Haemorrhagic Diseases
NCT06204042	Not specified	NOT_YET_RECRUITING	Multinational Glanzmann Study
NCT06820515	Not specified	RECRUITING	ATHNdataset Registry
NCT01319851	Not specified	TERMINATED	Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
NCT02179359	Not specified	TERMINATED	Hematopoietic Stem Cell Transplant for High Risk Hemoglobinopathies
NCT03372993	Not specified	COMPLETED	Prospective, Non-interventional Study to Evaluate Immunogenicity of AryoSeven
NCT04595617	Not specified	COMPLETED	Anti-αIIbβ3 Immunization in Glanzmann Thrombasthenia: Prevalence and Associated Risk Factors: Thrombasthenia Anti-αIIbβ3 Antibodies Study (TAAS)
NCT05315232	Not specified	COMPLETED	The Experiences of People Who Live With Glanzmanns Thrombasthenia.
NCT06234813	Not specified	COMPLETED	Targeting TFPI With Concizumab to Improve Haemostasis in Glanzmann Thrombasthenia Patients: an in Vitro Study

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ALEFACEPT	4	1
CONCIZUMAB	4	1
FLUDARABINE PHOSPHATE	4	1