Thrombophilia, familial, due to decreased release of tissue plasminogen activator

Summary

Thrombophilia, familial, due to decreased release of tissue plasminogen activator (MONDO:0012872) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	thrombophilia, familial, due to decreased release of tissue plasminogen activator
Mondo ID	MONDO:0012872
MeSH	C567341
OMIM	612348
DOID	DOID:0111906
UMLS	C2676721
MedGen	393574
GARD	0024894
Is cancer (heuristic)	no

Also known as: hyperfibrinolysis, familial, due to increased release of plat · THPH9 · thrombophilia, familial, due to decreased release of PLAT · thrombophilia, familial, due to decreased release of tissue plasminogen activator

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood coagulation disease › thrombophilia › inherited thrombophilia › thrombophilia, familial, due to decreased release of tissue plasminogen activator

Related subtypes (11): factor 5 excess with spontaneous thrombosis, thrombophilia due to thrombin defect, thrombophilia due to activated protein C resistance, thrombophilia, X-linked, due to factor 9 defect, heparin cofactor 2 deficiency, hereditary thrombophilia due to congenital histidine-rich (poly-L) glycoprotein deficiency, hereditary antithrombin deficiency, thrombomodulin-related bleeding disorder, hereditary thrombophilia due to congenital protein S deficiency, hereditary thrombophilia due to congenital protein C deficiency, thrombophilia, X-linked, due to factor 8 defect

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · 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
PLAT	Moderate	Autosomal recessive	thrombophilia, familial, due to decreased release of tissue plasminogen activator

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PLAT	Orphanet:480528	Lethal hydranencephaly-diaphragmatic hernia syndrome

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
PLAT	HGNC:9051	ENSG00000104368	P00750	Tissue-type plasminogen activator	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PLAT	Tissue-type plasminogen activator	Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen.

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PLAT	Protease	yes	3.4.21.68	Kringle, Fibronectin_type1, EGF

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
pancreatic ductal cell	1
stromal cell of endometrium	1
urethra	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PLAT	273	ubiquitous	marker	stromal cell of endometrium, pancreatic ductal cell, urethra

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PLAT	3,028

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PLAT	P00750	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Dissolution of Fibrin Clot	1	815.7×	0.002	PLAT
Signaling by PDGF	1	253.8×	0.004	PLAT

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
trans-synaptic signaling by BDNF, modulating synaptic transmission	1	5617.3×	0.002	PLAT
prevention of polyspermy	1	2808.7×	0.002	PLAT
negative regulation of plasminogen activation	1	2407.4×	0.002	PLAT
smooth muscle cell migration	1	1872.4×	0.002	PLAT
negative regulation of fibrinolysis	1	1404.3×	0.002	PLAT
plasminogen activation	1	1296.3×	0.002	PLAT
fibrinolysis	1	842.6×	0.002	PLAT
negative regulation of proteolysis	1	674.1×	0.002	PLAT
platelet-derived growth factor receptor signaling pathway	1	561.7×	0.003	PLAT
protein modification process	1	244.2×	0.005	PLAT
blood coagulation	1	173.7×	0.007	PLAT
response to hypoxia	1	95.8×	0.011	PLAT
proteolysis	1	34.2×	0.029	PLAT

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
PLAT	ARGATROBAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PLAT	8	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ARGATROBAN	4	PLAT
MELAGATRAN	4	PLAT
TRANEXAMIC ACID	4	PLAT
MILVEXIAN	3	PLAT
DABIGATRAN	3	PLAT
GABEXATE	3	PLAT
LETAXABAN	2	PLAT
EFEGATRAN	2	PLAT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PLAT	249	Binding:243, Functional:5, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PLAT	3.4.21.68	t-Plasminogen activator

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PLAT	249

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

8 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)
ARGATROBAN	4	PLAT
MELAGATRAN	4	PLAT
TRANEXAMIC ACID	4	PLAT
MILVEXIAN	3	PLAT
DABIGATRAN	3	PLAT
GABEXATE	3	PLAT
LETAXABAN	2	PLAT
EFEGATRAN	2	PLAT

Druggability pyramid

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

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