Fetomaternal alloimmune thrombocytopenia 1

Summary

Fetomaternal alloimmune thrombocytopenia 1 (MONDO:0980723) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	fetomaternal alloimmune thrombocytopenia 1
Mondo ID	MONDO:0980723
OMIM	621264
UMLS	C1868202
MedGen	356917
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › hemorrhagic disease › fetal and neonatal alloimmune thrombocytopenia › fetomaternal alloimmune thrombocytopenia 1

Related subtypes (2): fetomaternal alloimmune thrombocytopenia 2, fetomaternal alloimmune thrombocytopenia 3

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

5 retrieved; paginated sample, class counts are floors:

4 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
4072833	ITGB3, GLN158ARG (rs748901429)	ITGB3	Pathogenic	no assertion criteria provided
4072834	ITGB3, LYS606ASN	ITGB3	Pathogenic	no assertion criteria provided
4072835	ITGB3, LYS163GLN	ITGB3	Pathogenic	no assertion criteria provided
4072836	ITGB3, ASN174SER (rs879083862)	ITGB3	Pathogenic	no assertion criteria provided
4279596	NM_000212.3(ITGB3):c.310_311delinsCT (p.Ser104Leu)	ITGB3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ITGB3	HGNC:6156	ENSG00000259207	P05106	Integrin beta-3	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: 1 · 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	1	1.8×	0.558

Per-gene assignment

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

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ITGB3	199	ubiquitous	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITGB3	3,274

Structural data

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

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 1 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: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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

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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.