Bleeding disorder, platelet-type, 22

Summary

Bleeding disorder, platelet-type, 22 (MONDO:0032765) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	bleeding disorder, platelet-type, 22
Mondo ID	MONDO:0032765
OMIM	618462
UMLS	C5193111
MedGen	1673822
GARD	0025737
Is cancer (heuristic)	no

Also known as: BDPLT22

Data availability: 4 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 › bleeding disorder, platelet-type, 22

Related subtypes (27): gray platelet syndrome, primary release disorder of platelets, platelet-type von Willebrand disease, platelet-type bleeding disorder 16, 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, 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

4 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
633783	NM_017449.5(EPHB2):c.2233C>T (p.Arg745Cys)	EPHB2	Pathogenic	no assertion criteria provided
3068032	NM_017449.5(EPHB2):c.*174_*181dup	EPHB2	Uncertain significance	criteria provided, single submitter
3391021	NM_017449.5(EPHB2):c.2384C>A (p.Pro795Gln)	EPHB2	Uncertain significance	criteria provided, single submitter
3893102	NM_017449.5(EPHB2):c.*214_*215del	EPHB2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 1 · 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
EPHB2	Moderate	Autosomal recessive	bleeding disorder, platelet-type, 22	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EPHB2	Orphanet:1331	Familial prostate cancer

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
EPHB2	HGNC:3393	ENSG00000133216	P29323	Ephrin type-B receptor 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EPHB2	Ephrin type-B receptor 2	Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EPHB2	Kinase	yes	2.7.10.1	Prot_kinase_dom, EPH_LBD, Ser-Thr/Tyr_kinase_cat_dom

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
cortical plate	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EPHB2	214	ubiquitous	marker	ganglionic eminence, ventricular zone, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EPHB2	3,042

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
EPHB2	P29323	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Ephrin signaling	1	571.0×	0.008	EPHB2
EPHB-mediated forward signaling	1	265.6×	0.008	EPHB2
EPH-ephrin mediated repulsion of cells	1	219.6×	0.008	EPHB2
EPH-Ephrin signaling	1	165.5×	0.008	EPHB2
L1CAM interactions	1	120.2×	0.008	EPHB2

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 T-helper 17 type immune response	1	16852.0×	0.002	EPHB2
neuron projection retraction	1	8426.0×	0.002	EPHB2
negative regulation of glutamate receptor signaling pathway	1	8426.0×	0.002	EPHB2
hindbrain tangential cell migration	1	5617.3×	0.002	EPHB2
vesicle-mediated intercellular transport	1	5617.3×	0.002	EPHB2
regulation of body fluid levels	1	4213.0×	0.002	EPHB2
regulation of behavioral fear response	1	4213.0×	0.002	EPHB2
optic nerve morphogenesis	1	3370.4×	0.002	EPHB2
postsynaptic membrane assembly	1	2407.4×	0.002	EPHB2
tight junction assembly	1	2407.4×	0.002	EPHB2
central nervous system projection neuron axonogenesis	1	1872.4×	0.002	EPHB2
regulation of blood coagulation	1	1872.4×	0.002	EPHB2
positive regulation of long-term neuronal synaptic plasticity	1	1872.4×	0.002	EPHB2
positive regulation of synaptic plasticity	1	1532.0×	0.002	EPHB2
positive regulation of glutamate receptor signaling pathway	1	1532.0×	0.002	EPHB2
regulation of receptor signaling pathway via JAK-STAT	1	1404.3×	0.002	EPHB2
phosphorylation	1	1296.3×	0.002	EPHB2
negative regulation of axonogenesis	1	1296.3×	0.002	EPHB2
dendritic spine development	1	1203.7×	0.002	EPHB2
neuron projection maintenance	1	1123.5×	0.002	EPHB2
regulation of filopodium assembly	1	1053.2×	0.002	EPHB2
urogenital system development	1	991.3×	0.002	EPHB2
commissural neuron axon guidance	1	991.3×	0.002	EPHB2
axonal fasciculation	1	936.2×	0.002	EPHB2
dendritic spine morphogenesis	1	887.0×	0.002	EPHB2
positive regulation of dendritic spine morphogenesis	1	887.0×	0.002	EPHB2
corpus callosum development	1	842.6×	0.002	EPHB2
retinal ganglion cell axon guidance	1	766.0×	0.002	EPHB2
camera-type eye morphogenesis	1	766.0×	0.002	EPHB2
positive regulation of protein localization to cell surface	1	766.0×	0.002	EPHB2

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
EPHB2	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EPHB2	30	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	EPHB2
FEDRATINIB	4	EPHB2
TIVOZANIB	4	EPHB2
SORAFENIB	4	EPHB2
DASATINIB ANHYDROUS	4	EPHB2
VANDETANIB	4	EPHB2
NILOTINIB	4	EPHB2
BOSUTINIB	4	EPHB2
DASATINIB	4	EPHB2
SARACATINIB	3	EPHB2
LINIFANIB	3	EPHB2
CANERTINIB	3	EPHB2
TESEVATINIB	3	EPHB2
POZIOTINIB	3	EPHB2
LESTAURTINIB	3	EPHB2
DORAMAPIMOD	2	EPHB2
FORETINIB	2	EPHB2
REBASTINIB	2	EPHB2
BAFETINIB	2	EPHB2
SAPITINIB	2	EPHB2
GOLVATINIB	2	EPHB2
DANUSERTIB	2	EPHB2
TG100-801	2	EPHB2
R-406	2	EPHB2
MILCICLIB	2	EPHB2
TOZASERTIB	2	EPHB2
TAK-901	1	EPHB2
XL-228	1	EPHB2
CYC-116	1	EPHB2
AST-487	1	EPHB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
EPHB2	312	Binding:311, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EPHB2	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
EPHB2	312

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

30 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)
PONATINIB	4	EPHB2
FEDRATINIB	4	EPHB2
TIVOZANIB	4	EPHB2
SORAFENIB	4	EPHB2
DASATINIB ANHYDROUS	4	EPHB2
VANDETANIB	4	EPHB2
NILOTINIB	4	EPHB2
BOSUTINIB	4	EPHB2
DASATINIB	4	EPHB2
SARACATINIB	3	EPHB2
LINIFANIB	3	EPHB2
CANERTINIB	3	EPHB2
TESEVATINIB	3	EPHB2
POZIOTINIB	3	EPHB2
LESTAURTINIB	3	EPHB2
DORAMAPIMOD	2	EPHB2
FORETINIB	2	EPHB2
REBASTINIB	2	EPHB2
BAFETINIB	2	EPHB2
SAPITINIB	2	EPHB2
GOLVATINIB	2	EPHB2
DANUSERTIB	2	EPHB2
TG100-801	2	EPHB2
R-406	2	EPHB2
MILCICLIB	2	EPHB2
TOZASERTIB	2	EPHB2
TAK-901	1	EPHB2
XL-228	1	EPHB2
CYC-116	1	EPHB2
AST-487	1	EPHB2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	EPHB2
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.