Fetomaternal alloimmune thrombocytopenia 2

Summary

Fetomaternal alloimmune thrombocytopenia 2 (MONDO:0980724) is a disease caused by ITGA2B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ITGA2B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	fetomaternal alloimmune thrombocytopenia 2
Mondo ID	MONDO:0980724
OMIM	621266
Is cancer (heuristic)	no

Data availability: 4 ClinVar variants · 1 GenCC gene-disease record.

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 2

Related subtypes (2): fetomaternal alloimmune thrombocytopenia 1, 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

4 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 benign, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
4072840	ITGA2B, THR650MET	ITGA2B	Pathogenic	no assertion criteria provided
4072841	ITGA2B, VAL771LEU	ITGA2B	Pathogenic	no assertion criteria provided
50233	NM_000419.5(ITGA2B):c.3076C>T (p.Arg1026Trp)	ITGA2B	Uncertain significance	reviewed by expert panel
4072839	ITGA2B, VAL868MET	ITGA2B	Benign	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · 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
ITGA2B	Strong	Autosomal dominant	fetomaternal alloimmune thrombocytopenia 2	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

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
ITGA2B	HGNC:6138	ENSG00000005961	P08514	Integrin alpha-IIb	gencc,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.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

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

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
ITGA2B	182	broad	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITGA2B	2,486

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ITGA2B	P08514	78

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 37. 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
Fibrin formation	1	878.5×	0.011	ITGA2B
p130Cas linkage to MAPK signaling for integrins	1	761.3×	0.011	ITGA2B
GRB2:SOS provides linkage to MAPK signaling for Integrins	1	713.8×	0.011	ITGA2B
Signal transduction by L1	1	519.1×	0.011	ITGA2B
Platelet Aggregation (Plug Formation)	1	439.2×	0.011	ITGA2B
Integrin signaling	1	423.0×	0.011	ITGA2B
Signaling by RAS mutants	1	423.0×	0.011	ITGA2B
Signaling by high-kinase activity BRAF mutants	1	317.2×	0.011	ITGA2B
MAP2K and MAPK activation	1	285.5×	0.011	ITGA2B
Signaling by RAF1 mutants	1	278.5×	0.011	ITGA2B
Signaling by moderate kinase activity BRAF mutants	1	253.8×	0.011	ITGA2B
Paradoxical activation of RAF signaling by kinase inactive BRAF	1	253.8×	0.011	ITGA2B
Signaling downstream of RAS mutants	1	253.8×	0.011	ITGA2B
Oncogenic MAPK signaling	1	248.3×	0.011	ITGA2B
Signaling by BRAF and RAF1 fusions	1	170.4×	0.014	ITGA2B
Response to elevated platelet cytosolic Ca2+	1	163.1×	0.014	ITGA2B
ECM proteoglycans	1	150.3×	0.014	ITGA2B
Transcriptional regulation by RUNX1	1	146.4×	0.014	ITGA2B
Integrin cell surface interactions	1	134.3×	0.014	ITGA2B
MAPK1/MAPK3 signaling	1	131.3×	0.014	ITGA2B
L1CAM interactions	1	120.2×	0.014	ITGA2B
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1	120.2×	0.014	ITGA2B
Platelet activation, signaling and aggregation	1	105.7×	0.015	ITGA2B
MAPK family signaling cascades	1	102.9×	0.015	ITGA2B
Platelet degranulation	1	87.8×	0.017	ITGA2B
Extracellular matrix organization	1	63.1×	0.022	ITGA2B
RAF/MAP kinase cascade	1	61.1×	0.022	ITGA2B
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.023	ITGA2B
Axon guidance	1	45.1×	0.028	ITGA2B
Nervous system development	1	42.9×	0.029	ITGA2B

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
positive regulation of leukocyte migration	1	991.3×	0.005	ITGA2B
cell-matrix adhesion	1	163.6×	0.010	ITGA2B
integrin-mediated signaling pathway	1	160.5×	0.010	ITGA2B
cell-cell adhesion	1	101.5×	0.012	ITGA2B
angiogenesis	1	62.4×	0.016	ITGA2B

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
ITGA2B	EPTIFIBATIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ITGA2B	14	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
EPTIFIBATIDE	4	ITGA2B
ASPIRIN	4	ITGA2B
TIROFIBAN	4	ITGA2B
NAFAMOSTAT	3	ITGA2B
CILENGITIDE	3	ITGA2B
LAMIFIBAN	2	ITGA2B
ROXIFIBAN	2	ITGA2B
FRADAFIBAN	2	ITGA2B
LOTRAFIBAN	2	ITGA2B
SIBRAFIBAN	2	ITGA2B
ORBOFIBAN	2	ITGA2B
XEMILOFIBAN	2	ITGA2B
GANTOFIBAN	2	ITGA2B
ELAROFIBAN	2	ITGA2B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
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

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

14 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
ASPIRIN	4	ITGA2B
TIROFIBAN	4	ITGA2B
NAFAMOSTAT	3	ITGA2B
CILENGITIDE	3	ITGA2B
LAMIFIBAN	2	ITGA2B
ROXIFIBAN	2	ITGA2B
FRADAFIBAN	2	ITGA2B
LOTRAFIBAN	2	ITGA2B
SIBRAFIBAN	2	ITGA2B
ORBOFIBAN	2	ITGA2B
XEMILOFIBAN	2	ITGA2B
GANTOFIBAN	2	ITGA2B
ELAROFIBAN	2	ITGA2B

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ITGA2B
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.