Inherited bleeding disorder, platelet-type

Summary

Inherited bleeding disorder, platelet-type (MONDO:0000009) is a disease (an umbrella term covering 28 Mondo subtypes) with 4 cohort genes and 12 clinical trials. Top therapeutic interventions include avatrombopag, eltrombopag, and rifaximin.

At a glance

• Umbrella term: 28 Mondo subtypes
• Cohort genes: 4
• ClinVar variants: 4
• Clinical trials: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	inherited bleeding disorder, platelet-type
Mondo ID	MONDO:0000009
OMIM	231200
DOID	DOID:2218
UMLS	C0005818
MedGen	610
GARD	0022702
Is cancer (heuristic)	no

Also known as: bleeding disorder, platelet-type · blood platelet disease · platelet disorder

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

Disease family

An umbrella term covering 28 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › hemorrhagic disease › inherited bleeding disorder, platelet-type

Related subtypes (27): 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, fetal and neonatal alloimmune thrombocytopenia, hereditary von Willebrand disease, acquired von willebrand syndrome, prothrombin deficiency, hemophilia B leyden

Subtypes (28): 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, 22, 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:

1 conflicting classifications of pathogenicity, 1 pathogenic, 1 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
626941	NM_014915.3(ANKRD26):c.-126T>C	ANKRD26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
417961	NM_001754.5(RUNX1):c.497G>A (p.Arg166Gln)	RUNX1	Pathogenic	reviewed by expert panel
632008	NM_001001548.3(CD36):c.380C>G (p.Ser127Ter)	CD36	Likely pathogenic	criteria provided, single submitter
13535	NM_001001548.3(CD36):c.268C>T (p.Pro90Ser)	CD36	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 5 · 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
RGS18	Limited	Autosomal dominant	inherited bleeding disorder, platelet-type

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RUNX1	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
RUNX1	Orphanet:521	Chronic myeloid leukemia
RUNX1	Orphanet:71290	Familial platelet disorder with associated myeloid malignancy
RUNX1	Orphanet:98850	Aggressive systemic mastocytosis
ANKRD26	Orphanet:168629	Autosomal thrombocytopenia with normal platelets

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RGS18	HGNC:14261	ENSG00000150681	Q9NS28	Regulator of G-protein signaling 18	gencc
RUNX1	HGNC:10471	ENSG00000159216	Q01196	Runt-related transcription factor 1	clinvar
CD36	HGNC:1663	ENSG00000135218	P16671	Platelet glycoprotein 4	clinvar
ANKRD26	HGNC:29186	ENSG00000107890	Q9UPS8	Ankyrin repeat domain-containing protein 26	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RGS18	Regulator of G-protein signaling 18	Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form.
RUNX1	Runt-related transcription factor 1	Forms the heterodimeric complex core-binding factor (CBF) with CBFB.
CD36	Platelet glycoprotein 4	Multifunctional glycoprotein that acts as a receptor for a broad range of ligands.
ANKRD26	Ankyrin repeat domain-containing protein 26	Acts as a regulator of adipogenesis.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 2 · 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
Scaffold/PPI	1	4.3×	0.605
Transcription factor	1	2.1×	0.605
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RGS18	Other/Unknown	no		RGS, RGS_subdom1/3, RGS_sf
RUNX1	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
CD36	Other/Unknown	no		CD36_fam, CD36/SCARB1/SNMP1
ANKRD26	Scaffold/PPI	no		Ankyrin_rpt, DUF3496, Ankyrin_rpt-contain_sf

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
monocyte	2
granulocyte	1
leukocyte	1
epithelium of bronchus	1
mucosa of paranasal sinus	1
olfactory segment of nasal mucosa	1
adipose tissue of abdominal region	1
omental fat pad	1
calcaneal tendon	1
male germ line stem cell (sensu Vertebrata) in testis	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RGS18	174	broad	marker	monocyte, leukocyte, granulocyte
RUNX1	253	ubiquitous	marker	olfactory segment of nasal mucosa, epithelium of bronchus, mucosa of paranasal sinus
CD36	252	broad	marker	adipose tissue of abdominal region, omental fat pad, monocyte
ANKRD26	206	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, sural nerve

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CD36	5,268
RUNX1	4,994
RGS18	2,161
ANKRD26	1,721

Intra-cohort edges

A	B	Sources
ANKRD26	RUNX1	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RUNX1	Q01196	5
RGS18	Q9NS28	3
CD36	P16671	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ANKRD26	Q9UPS8	62.91

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 95. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Free fatty acids regulate insulin secretion	1	951.7×	0.022	CD36
Intracellular metabolism of fatty acids regulates insulin secretion	1	951.7×	0.022	CD36
RUNX3 regulates RUNX1-mediated transcription	1	951.7×	0.022	RUNX1
RUNX1 regulates expression of components of tight junctions	1	571.0×	0.022	RUNX1
RUNX1 regulates transcription of genes involved in interleukin signaling	1	571.0×	0.022	RUNX1
RUNX2 regulates genes involved in differentiation of myeloid cells	1	571.0×	0.022	RUNX1
RUNX1 regulates estrogen receptor mediated transcription	1	475.8×	0.022	RUNX1
RUNX1 regulates transcription of genes involved in BCR signaling	1	475.8×	0.022	RUNX1
RUNX1 regulates transcription of genes involved in WNT signaling	1	475.8×	0.022	RUNX1
Cross-presentation of particulate exogenous antigens (phagosomes)	1	356.9×	0.024	CD36
RUNX1 regulates transcription of genes involved in differentiation of myeloid cells	1	356.9×	0.024	RUNX1
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)	1	285.5×	0.024	RUNX1
RUNX1 regulates transcription of genes involved in differentiation of keratinocytes	1	285.5×	0.024	RUNX1
RUNX3 regulates p14-ARF	1	285.5×	0.024	RUNX1
Scavenging by Class B Receptors	1	259.6×	0.024	CD36
Diseases of Immune System	1	219.6×	0.024	CD36
Diseases associated with the TLR signaling cascade	1	219.6×	0.024	CD36
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)	1	219.6×	0.024	RUNX1
SLC-mediated transport of organic cations	1	190.3×	0.025	RUNX1
R-HSA-549132	1	190.3×	0.025	RUNX1
Regulation of RUNX1 Expression and Activity	1	167.9×	0.027	RUNX1
MyD88 deficiency (TLR2/4)	1	150.3×	0.029	CD36
IRAK4 deficiency (TLR2/4)	1	142.8×	0.029	CD36
Binding and Uptake of Ligands by Scavenger Receptors	1	135.9×	0.029	CD36
Regulation of TLR by endogenous ligand	1	124.1×	0.031	CD36
Pre-NOTCH Expression and Processing	1	92.1×	0.040	RUNX1
Antigen processing-Cross presentation	1	79.3×	0.044	CD36
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	75.1×	0.044	RUNX1
Transcriptional regulation by RUNX3	1	68.0×	0.044	RUNX1
SARS-CoV-1 activates/modulates innate immune responses	1	68.0×	0.044	RUNX1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
short-chain fatty acid transport	1	4213.0×	0.006	CD36
oxidised low-density lipoprotein particle clearance	1	4213.0×	0.006	CD36
regulation of connective tissue replacement	1	4213.0×	0.006	RUNX1
positive regulation of blood microparticle formation	1	2106.5×	0.006	CD36
myeloid leukocyte differentiation	1	1404.3×	0.006	RUNX1
regulation of plasminogen activation	1	1404.3×	0.006	RUNX1
low-density lipoprotein particle mediated signaling	1	1404.3×	0.006	CD36
response to linoleic acid	1	1404.3×	0.006	CD36
regulation of action potential	1	1404.3×	0.006	CD36
long-chain fatty acid import across plasma membrane	1	1053.2×	0.006	CD36
regulation of lipopolysaccharide-mediated signaling pathway	1	1053.2×	0.006	CD36
triglyceride transport	1	1053.2×	0.006	CD36
plasma lipoprotein particle clearance	1	1053.2×	0.006	CD36
negative regulation of CD4-positive, alpha-beta T cell differentiation	1	1053.2×	0.006	RUNX1
cardiac muscle tissue regeneration	1	1053.2×	0.006	RUNX1
cellular response to diacyl bacterial lipopeptide	1	1053.2×	0.006	CD36
positive regulation of extracellular matrix organization	1	1053.2×	0.006	RUNX1
positive regulation of CD8-positive, alpha-beta T cell differentiation	1	842.6×	0.006	RUNX1
regulation of cardiac muscle cell proliferation	1	842.6×	0.006	RUNX1
lipid transport across blood-brain barrier	1	842.6×	0.006	CD36
positive regulation of granulocyte differentiation	1	702.2×	0.006	RUNX1
response to stilbenoid	1	702.2×	0.006	CD36
cholesterol import	1	702.2×	0.006	CD36
regulation of removal of superoxide radicals	1	702.2×	0.006	CD36
production of molecular mediator involved in inflammatory response	1	601.9×	0.006	CD36
positive regulation of cholesterol storage	1	601.9×	0.006	CD36
response to lipid	1	601.9×	0.006	CD36
phagocytosis, recognition	1	526.6×	0.006	CD36
negative regulation of granulocyte differentiation	1	526.6×	0.006	RUNX1
cellular response to hydroperoxide	1	526.6×	0.006	CD36

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 4 evidence-associated genes (50%) 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
RUNX1	APOMORPHINE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RUNX1	2	4
RGS18	0	0
CD36	0	0
ANKRD26	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
APOMORPHINE HYDROCHLORIDE	4	RUNX1
MOLIBRESIB	2	RUNX1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RUNX1	20	Binding:17, Functional:3
CD36	6	Binding:5, Functional:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

2 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)
APOMORPHINE HYDROCHLORIDE	4	RUNX1
MOLIBRESIB	2	RUNX1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RUNX1
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	3	RGS18, CD36, ANKRD26

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ANKRD26	0	RUNX1
RGS18	0	—
CD36	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 12.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	7
PHASE2	4
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06630572	PHASE4	TERMINATED	Rifaximin in Cirrhosis: Effects on Endotoxin and Haemostatic Indexes
NCT06261060	PHASE2	RECRUITING	Low-Dose Sirolimus to Increase Hematopoietic Function in Patients With RUNX1 Familial Platelet Disorder
NCT01880047	PHASE2	COMPLETED	Safety and Efficacy of Eltrombopag at Escalated Doses
NCT04312789	PHASE2	WITHDRAWN	Avatrombopag for the Treatment of Thrombocytopenia After Donor Hematopoietic Stem Cell Transplant
NCT05143892	PHASE2	UNKNOWN	Avatrombopag to Promote Platelet Engraftment After Allo-HSCT
NCT04398628	Not specified	RECRUITING	ATHN Transcends: A Natural History Study of Non-Neoplastic Hematologic Disorders
NCT05985668	Not specified	RECRUITING	Towards Improved Diagnostics for Suspected Platelet Function Disorders
NCT06691581	Not specified	ACTIVE_NOT_RECRUITING	Italian Study for Congenital Platelet Disorders
NCT01839968	Not specified	COMPLETED	Ex-Vivo Reversion of Platelet Inhibition Induced by Prasugrel
NCT02979158	Not specified	COMPLETED	Preoperative Dual Antiplatelet Therapy: Platelet Function and Influence of Cardiopulmonary Bypass
NCT04419987	Not specified	UNKNOWN	Study of Constitutional Platelet Disease
NCT04842760	Not specified	UNKNOWN	PLATELET Function Assay With Flow Imaging on ImageSTREAM Cytometer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
AVATROMBOPAG	4	2
ELTROMBOPAG	4	1
RIFAXIMIN	4	1