Fetal and neonatal alloimmune thrombocytopenia

Summary

Fetal and neonatal alloimmune thrombocytopenia (MONDO:0019415) is a disease with 2 cohort genes and 5 clinical trials.

At a glance

• Prevalence: 1-5 / 10 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 2
• Phenotypes (HPO): 17
• Clinical trials: 5

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	39.6307	Worldwide	Validated
Prevalence at birth	6-9 / 10 000	66.6667	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0004809	Neonatal alloimmune thrombocytopenia	Obligate (100%)
HP:0000967	Petechiae	Frequent (30-79%)
HP:0000979	Purpura	Frequent (30-79%)
HP:0001892	Abnormal bleeding	Frequent (30-79%)
HP:0007420	Spontaneous hematomas	Frequent (30-79%)
HP:0012541	Cephalohematoma	Frequent (30-79%)
HP:0000790	Hematuria	Occasional (5-29%)
HP:0002170	Intracranial hemorrhage	Occasional (5-29%)
HP:0002239	Gastrointestinal hemorrhage	Occasional (5-29%)
HP:0002249	Melena	Occasional (5-29%)
HP:0031364	Ecchymosis	Occasional (5-29%)
HP:0000618	Blindness	Very rare (<1-4%)
HP:0000707	Abnormality of the nervous system	Very rare (<1-4%)
HP:0001263	Global developmental delay	Very rare (<1-4%)
HP:0002138	Subarachnoid hemorrhage	Very rare (<1-4%)
HP:0008619	Bilateral sensorineural hearing impairment	Very rare (<1-4%)
HP:0100021	Cerebral palsy	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	fetal and neonatal alloimmune thrombocytopenia
Mondo ID	MONDO:0019415
OMIM	621264
Orphanet	853
SNOMED CT	240305000
UMLS	C3854603
MedGen	1720701
GARD	0002295
NORD	91170
Is cancer (heuristic)	no

Also known as: NAIT

Data availability: 2 ClinVar variants · 1 cell line.

Disease family

An umbrella term covering 3 Mondo subtypes.

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

Related subtypes (27): inherited bleeding disorder, platelet-type, factor VII deficiency, factor X deficiency, purpura, vascular hemostatic disease, congenital factor V deficiency, congenital high-molecular-weight kininogen deficiency, congenital factor XII deficiency, alpha-2-plasmin inhibitor deficiency, hemophilia A, hemophilia B, East Texas bleeding disorder, congenital factor XI deficiency, inherited prekallikrein deficiency, congenital plasminogen activator inhibitor type 1 deficiency, thrombomodulin-related bleeding disorder, congenital vitamin K-dependent coagulation factors deficiency, hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation, multiple sclerosis-ichthyosis-factor VIII deficiency syndrome, congenital factor XIII deficiency, congenital fibrinogen deficiency, combined deficiency of factor V and factor VIII, acquired hemophilia, hereditary von Willebrand disease, acquired von willebrand syndrome, prothrombin deficiency, hemophilia B leyden

Subtypes (3): fetomaternal alloimmune thrombocytopenia 1, 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

2 retrieved; paginated sample, class counts are floors:

1 benign/likely benign, 1 association

ClinVar	Variant (HGVS)	Gene	Classification	Review
446505	NM_000212.3(ITGB3):c.1373A>G (p.Asp458Gly)	ITGB3	association	criteria provided, single submitter
353752	NM_002203.4(ITGA2):c.1594A>C (p.Ile532Leu)	ITGA2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ITGA2	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

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ITGA2	HGNC:6137	ENSG00000164171	P17301	Integrin alpha-2	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)
ITGA2	Integrin alpha-2	Integrin alpha-2/beta-1 is a receptor for laminin, collagen, collagen C-propeptides, fibronectin and E-cadherin.
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: 1 · Druggable fraction: 0.5

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	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ITGA2	Antibody/Immunoglobulin	yes		Integrin_alpha, VWF_A, FG-GAP
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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
epithelium of nasopharynx	1
nasopharynx	1
ventricular zone	1
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ITGA2	240	ubiquitous	marker	ventricular zone, epithelium of nasopharynx, nasopharynx
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
ITGA2	2,578

Intra-cohort edges

A	B	Sources
ITGA2	ITGB3	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ITGB3	P05106	123
ITGA2	P17301	17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 58. Enrichment computed across 2 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
Syndecan interactions	2	423.0×	3e-04	ITGA2, ITGB3
Non-integrin membrane-ECM interactions	2	154.3×	8e-04	ITGA2, ITGB3
ECM proteoglycans	2	150.3×	8e-04	ITGA2, ITGB3
Integrin cell surface interactions	2	134.3×	8e-04	ITGA2, ITGB3
L1CAM interactions	2	120.2×	8e-04	ITGA2, ITGB3
Extracellular matrix organization	2	63.1×	0.002	ITGA2, ITGB3
Signaling by Receptor Tyrosine Kinases	2	51.7×	0.003	ITGA2, ITGB3
Axon guidance	2	45.1×	0.003	ITGA2, ITGB3
Nervous system development	2	42.9×	0.003	ITGA2, ITGB3
Hemostasis	2	36.0×	0.004	ITGA2, ITGB3
CHL1 interactions	1	634.4×	0.008	ITGA2
PECAM1 interactions	1	439.2×	0.009	ITGB3
Fibrin formation	1	439.2×	0.009	ITGB3
Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition	1	439.2×	0.009	ITGA2
p130Cas linkage to MAPK signaling for integrins	1	380.7×	0.010	ITGB3
GRB2:SOS provides linkage to MAPK signaling for Integrins	1	356.9×	0.010	ITGB3
Platelet Adhesion to exposed collagen	1	335.9×	0.010	ITGA2
Mechanical load activates signaling by PIEZO1 and integrins in osteocytes	1	335.9×	0.010	ITGB3
MET promotes cell motility	1	300.5×	0.010	ITGA2
Signal transduction by L1	1	259.6×	0.011	ITGB3
Platelet Aggregation (Plug Formation)	1	219.6×	0.012	ITGB3
Integrin signaling	1	211.5×	0.012	ITGB3
Signaling by RAS mutants	1	211.5×	0.012	ITGB3
Developmental Biology	2	14.5×	0.012	ITGA2, ITGB3
Laminin interactions	1	190.3×	0.012	ITGA2
MET activates PTK2 signaling	1	190.3×	0.012	ITGA2
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	1	178.4×	0.012	ITGB3
Elastic fibre formation	1	167.9×	0.012	ITGB3
TGF-beta receptor signaling activates SMADs	1	163.1×	0.012	ITGB3
Signaling by high-kinase activity BRAF mutants	1	158.6×	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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mesodermal cell differentiation	2	1532.0×	4e-05	ITGA2, ITGB3
positive regulation of smooth muscle cell migration	2	991.3×	5e-05	ITGA2, ITGB3
cell-substrate adhesion	2	766.0×	5e-05	ITGA2, ITGB3
cell adhesion mediated by integrin	2	674.1×	5e-05	ITGA2, ITGB3
positive regulation of smooth muscle cell proliferation	2	330.4×	2e-04	ITGA2, ITGB3
cellular response to mechanical stimulus	2	216.1×	3e-04	ITGA2, ITGB3
blood coagulation	2	173.7×	4e-04	ITGA2, ITGB3
cell-matrix adhesion	2	163.6×	4e-04	ITGA2, ITGB3
integrin-mediated signaling pathway	2	160.5×	4e-04	ITGA2, ITGB3
regulation of serotonin uptake	1	8426.0×	0.001	ITGB3
positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathway	1	8426.0×	0.001	ITGB3
hypotonic response	1	4213.0×	0.002	ITGA2
negative regulation of lipoprotein metabolic process	1	4213.0×	0.002	ITGB3
regulation of trophoblast cell migration	1	4213.0×	0.002	ITGB3
maintenance of postsynaptic specialization structure	1	2808.7×	0.002	ITGB3
regulation of postsynaptic neurotransmitter receptor diffusion trapping	1	2808.7×	0.002	ITGB3
negative regulation of lipid transport	1	2106.5×	0.002	ITGB3
response to L-ascorbic acid	1	2106.5×	0.002	ITGA2
tube development	1	2106.5×	0.002	ITGB3
apolipoprotein A-I-mediated signaling pathway	1	2106.5×	0.002	ITGB3
collagen-activated signaling pathway	1	2106.5×	0.002	ITGA2
response to parathyroid hormone	1	2106.5×	0.002	ITGA2
positive regulation of cell projection organization	1	1685.2×	0.002	ITGA2
cell-substrate junction assembly	1	1404.3×	0.003	ITGB3
positive regulation of glomerular mesangial cell proliferation	1	1404.3×	0.003	ITGB3
cell adhesion	2	37.5×	0.003	ITGA2, ITGB3
substrate-dependent cell migration	1	1203.7×	0.003	ITGA2
positive regulation of transmission of nerve impulse	1	1203.7×	0.003	ITGA2
response to amine	1	936.2×	0.003	ITGA2
smooth muscle cell migration	1	936.2×	0.003	ITGB3

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
ITGA2	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
ITGA2	21	Binding:20, Functional:1

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: 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	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	1	ITGA2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
ITGA2	21	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06435845	PHASE2	TERMINATED	Phase 2 Study on the Pharmacokinetics and Safety of RLYB212 in Pregnant Women at Higher Risk for HPA-1a Alloimmunization
NCT03561909	Not specified	COMPLETED	Kinetics of Blood Platelets Transfused to Healthy Subjects
NCT04067375	Not specified	COMPLETED	Towards Routine HPA-screening In Pregnancy to Prevent FNAIT
NCT04529382	Not specified	UNKNOWN	Neurodevelopmental Outcome After Fetal Neonatal AlloImmune Thrombocytopenia
NCT05345561	Not specified	COMPLETED	Study to Assess the Occurrence of HPA-1a Alloimmunization in Women With Higher Risk for Fetal and Neonatal Alloimmune Thrombocytopenia