Platelet-type bleeding disorder 14

Summary

Platelet-type bleeding disorder 14 (MONDO:0013597) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	platelet-type bleeding disorder 14
Mondo ID	MONDO:0013597
MeSH	C562866
OMIM	614158
DOID	DOID:0111047
SNOMED CT	234477002
UMLS	C0398635
MedGen	98307
GARD	0024935
Is cancer (heuristic)	no

Also known as: BDPLT14 · bleeding disorder, platelet-type, 14 · inherited bleeding disorder, platelet-type caused by mutation in TBXAS1 · TBXAS1 inherited bleeding disorder, platelet-type

Data availability: 3 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › hemorrhagic disease › inherited bleeding disorder, platelet-type › platelet-type bleeding disorder 14

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 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

3 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity, 1 likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
626225	NM_001061.7(TBXAS1):c.580_581del (p.Ala194fs)	TBXAS1	Likely pathogenic	criteria provided, single submitter
626181	NM_001061.7(TBXAS1):c.1417G>T (p.Gly473Trp)	TBXAS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
838155	NM_001061.7(TBXAS1):c.251G>T (p.Arg84Leu)	TBXAS1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TBXAS1	Orphanet:1802	Ghosal hematodiaphyseal dysplasia

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
TBXAS1	HGNC:11609	ENSG00000059377	P24557	Thromboxane-A synthase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TBXAS1	Thromboxane-A synthase	Catalyzes the conversion of prostaglandin H2 (PGH2) to thromboxane A2 (TXA2), a potent inducer of blood vessel constriction and platelet aggregation.

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)
TBXAS1	Other/Unknown	no		Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS

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
TBXAS1	180	ubiquitous	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TBXAS1	2,072

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TBXAS1	P24557	91.50

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
Defective TBXAS1 causes GHDD	1	11420.0×	0.001	TBXAS1
Eicosanoids	1	951.7×	0.004	TBXAS1
Metabolic disorders of biological oxidation enzymes	1	878.5×	0.004	TBXAS1
Synthesis of Prostaglandins (PG) and Thromboxanes (TX)	1	761.3×	0.004	TBXAS1
Cytochrome P450 - arranged by substrate type	1	713.8×	0.004	TBXAS1
Arachidonate metabolism	1	571.0×	0.004	TBXAS1
Phase I - Functionalization of compounds	1	219.6×	0.008	TBXAS1
Fatty acid metabolism	1	131.3×	0.011	TBXAS1
Biological oxidations	1	129.8×	0.011	TBXAS1
Diseases of metabolism	1	80.4×	0.016	TBXAS1
Metabolism of lipids	1	31.6×	0.037	TBXAS1
Disease	1	13.1×	0.083	TBXAS1
Metabolism	1	11.6×	0.086	TBXAS1

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
prostanoid biosynthetic process	1	2407.4×	0.002	TBXAS1
icosanoid metabolic process	1	1872.4×	0.002	TBXAS1
intracellular chloride ion homeostasis	1	1685.2×	0.002	TBXAS1
prostaglandin biosynthetic process	1	1123.5×	0.002	TBXAS1
response to fatty acid	1	1053.2×	0.002	TBXAS1
positive regulation of vasoconstriction	1	601.9×	0.002	TBXAS1
long-chain fatty acid biosynthetic process	1	443.5×	0.003	TBXAS1
response to ethanol	1	146.5×	0.007	TBXAS1

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
TBXAS1	CLOTRIMAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TBXAS1	46	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CLOTRIMAZOLE	4	TBXAS1
CISPLATIN	4	TBXAS1
SAQUINAVIR	4	TBXAS1
AMPRENAVIR	4	TBXAS1
OZAGREL	4	TBXAS1
GRAMICIDIN	4	TBXAS1
ROSIGLITAZONE	4	TBXAS1
SULCONAZOLE	4	TBXAS1
OXICONAZOLE	4	TBXAS1
KETOCONAZOLE	4	TBXAS1
VINBLASTINE	4	TBXAS1
RITONAVIR	4	TBXAS1
NIFEDIPINE	4	TBXAS1
BITHIONOL	4	TBXAS1
3,3’,4’,5-TETRACHLOROSALICYLANILIDE	4	TBXAS1
TROGLITAZONE	4	TBXAS1
DIETHYLSTILBESTROL	4	TBXAS1
SULFASALAZINE	4	TBXAS1
TROVAFLOXACIN	4	TBXAS1
ERGOTAMINE	4	TBXAS1
AMINOGLUTETHIMIDE	4	TBXAS1
HEXACHLOROPHENE	4	TBXAS1
TANNIC ACID	4	TBXAS1
NELFINAVIR	4	TBXAS1
INDOMETHACIN	4	TBXAS1
ZAFIRLUKAST	4	TBXAS1
MONTELUKAST	4	TBXAS1
ECONAZOLE	4	TBXAS1
TAMOXIFEN	4	TBXAS1
MICONAZOLE	4	TBXAS1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TBXAS1	210	Binding:138, Functional:72

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TBXAS1	210

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)
CLOTRIMAZOLE	4	TBXAS1
CISPLATIN	4	TBXAS1
SAQUINAVIR	4	TBXAS1
AMPRENAVIR	4	TBXAS1
OZAGREL	4	TBXAS1
GRAMICIDIN	4	TBXAS1
ROSIGLITAZONE	4	TBXAS1
SULCONAZOLE	4	TBXAS1
OXICONAZOLE	4	TBXAS1
KETOCONAZOLE	4	TBXAS1
VINBLASTINE	4	TBXAS1
RITONAVIR	4	TBXAS1
NIFEDIPINE	4	TBXAS1
BITHIONOL	4	TBXAS1
3,3’,4’,5-TETRACHLOROSALICYLANILIDE	4	TBXAS1
TROGLITAZONE	4	TBXAS1
DIETHYLSTILBESTROL	4	TBXAS1
SULFASALAZINE	4	TBXAS1
TROVAFLOXACIN	4	TBXAS1
ERGOTAMINE	4	TBXAS1
AMINOGLUTETHIMIDE	4	TBXAS1
HEXACHLOROPHENE	4	TBXAS1
TANNIC ACID	4	TBXAS1
NELFINAVIR	4	TBXAS1
INDOMETHACIN	4	TBXAS1
ZAFIRLUKAST	4	TBXAS1
MONTELUKAST	4	TBXAS1
ECONAZOLE	4	TBXAS1
TAMOXIFEN	4	TBXAS1
MICONAZOLE	4	TBXAS1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TBXAS1
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.