Quebec platelet disorder

Summary

Quebec platelet disorder (MONDO:0011136) is a disease caused by PLAU (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: 1-9 / 1 000 000 (Specific population) [Orphanet-validated]
• Causal gene: PLAU (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 72

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.45	Specific population	Validated
Point prevalence	1-9 / 1 000 000	0.15	Canada	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Quebec platelet disorder
Mondo ID	MONDO:0011136
MeSH	C536260
OMIM	601709
Orphanet	220436
DOID	DOID:0111050
ICD-11	1618741944
UMLS	C1866423
MedGen	356528
GARD	0008345
Is cancer (heuristic)	no

Also known as: BDPLT5 · factor V Quebec · QPD · Quebec platelet disorder

Data availability: 72 ClinVar variants · 4 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 › Quebec platelet disorder

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, 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

72 retrieved; paginated sample, class counts are floors:

31 uncertain significance, 25 benign, 7 benign/likely benign, 4 conflicting classifications of pathogenicity, 3 likely benign, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1722380	NC_000010.10:g.(?75670858)(75677260_?)dup	C10orf55	Pathogenic	criteria provided, single submitter
29921	NC_000010.9:g.75329022_75406959dup	C10orf55	Pathogenic	no assertion criteria provided
300739	NM_002658.6(PLAU):c.17C>A (p.Ala6Glu)	C10orf55	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
300746	NM_002658.6(PLAU):c.308C>T (p.Thr103Met)	C10orf55	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
878609	NM_002658.6(PLAU):c.559A>G (p.Ile187Val)	C10orf55	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
300745	NM_002658.6(PLAU):c.236G>A (p.Arg79Gln)	PLAU	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029617	NM_002658.6(PLAU):c.1229C>T (p.Thr410Met)	C10orf55	Uncertain significance	criteria provided, single submitter
1696678	NM_002658.6(PLAU):c.467dup (p.Pro157fs)	C10orf55	Uncertain significance	criteria provided, single submitter
2434917	NM_002658.6(PLAU):c.754A>T (p.Met252Leu)	C10orf55	Uncertain significance	criteria provided, multiple submitters, no conflicts
2434918	NM_002658.6(PLAU):c.548A>G (p.Glu183Gly)	C10orf55	Uncertain significance	criteria provided, multiple submitters, no conflicts
2582777	NM_002658.6(PLAU):c.539T>C (p.Ile180Thr)	C10orf55	Uncertain significance	criteria provided, single submitter
300733	NM_002658.6(PLAU):c.-41G>A	C10orf55	Uncertain significance	criteria provided, single submitter
300734	NM_002658.6(PLAU):c.-32G>A	C10orf55	Uncertain significance	criteria provided, single submitter
300735	NM_002658.6(PLAU):c.-32+9C>G	C10orf55	Uncertain significance	criteria provided, multiple submitters, no conflicts
300747	NM_002658.6(PLAU):c.316G>C (p.Ala106Pro)	C10orf55	Uncertain significance	criteria provided, single submitter
300748	NM_002658.6(PLAU):c.368+6G>C	C10orf55	Uncertain significance	criteria provided, single submitter
300749	NM_002658.6(PLAU):c.581C>A (p.Ala194Glu)	C10orf55	Uncertain significance	criteria provided, single submitter
300755	NM_002658.6(PLAU):c.750G>C (p.Gly250=)	C10orf55	Uncertain significance	criteria provided, single submitter
300762	NM_002658.6(PLAU):c.*3G>A	C10orf55	Uncertain significance	criteria provided, single submitter
300766	NM_002658.6(PLAU):c.*176G>T	C10orf55	Uncertain significance	criteria provided, single submitter
300773	NM_002658.6(PLAU):c.*631C>T	C10orf55	Uncertain significance	criteria provided, single submitter
300774	NM_002658.6(PLAU):c.*688C>T	C10orf55	Uncertain significance	criteria provided, single submitter
300775	NM_002658.6(PLAU):c.*753C>T	C10orf55	Uncertain significance	criteria provided, single submitter
300777	NM_002658.6(PLAU):c.*880T>A	C10orf55	Uncertain significance	criteria provided, single submitter
300778	NM_002658.6(PLAU):c.*900A>G	C10orf55	Uncertain significance	criteria provided, single submitter
300779	NM_002658.3(PLAU):c.*935A>G	C10orf55	Uncertain significance	criteria provided, single submitter
3064536	NM_002658.6(PLAU):c.983A>G (p.Tyr328Cys)	C10orf55	Uncertain significance	criteria provided, single submitter
3780440	NM_002658.6(PLAU):c.680+5G>A	C10orf55	Uncertain significance	criteria provided, single submitter
877591	NM_002658.6(PLAU):c.194A>G (p.Asp65Gly)	C10orf55	Uncertain significance	criteria provided, single submitter
877647	NM_002658.6(PLAU):c.*309T>C	C10orf55	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
PLAU	Strong	Autosomal dominant	Quebec platelet disorder	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PLAU	Orphanet:220436	Quebec platelet disorder

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PLAU	HGNC:9052	ENSG00000122861	P00749	Urokinase-type plasminogen activator	gencc,clinvar
C10orf55	HGNC:31008	ENSG00000222047		chromosome 10 putative open reading frame 55	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PLAU	Urokinase-type plasminogen activator	Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.

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
Protease	1	18.3×	0.108
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PLAU	Protease	yes	3.4.21.73	Kringle, EGF, Trypsin_dom
C10orf55	Other/Unknown	no

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
islet of Langerhans	1
renal medulla	1
stromal cell of endometrium	1
left testis	1
right testis	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PLAU	242	ubiquitous	marker	renal medulla, stromal cell of endometrium, islet of Langerhans
C10orf55	122		marker	sperm, left testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PLAU	3,667
C10orf55	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PLAU	P00749	156

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 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	PLAU
Neutrophil degranulation	1	23.1×	0.043	PLAU

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 smooth muscle cell-matrix adhesion	1	16852.0×	0.001	PLAU
regulation of plasminogen activation	1	5617.3×	0.001	PLAU
urokinase plasminogen activator signaling pathway	1	4213.0×	0.001	PLAU
regulation of fibrinolysis	1	4213.0×	0.001	PLAU
regulation of wound healing	1	3370.4×	0.001	PLAU
negative regulation of plasminogen activation	1	2407.4×	0.001	PLAU
regulation of smooth muscle cell migration	1	2407.4×	0.001	PLAU
regulation of integrin-mediated signaling pathway	1	2106.5×	0.001	PLAU
smooth muscle cell migration	1	1872.4×	0.001	PLAU
regulation of cell adhesion mediated by integrin	1	1872.4×	0.001	PLAU
negative regulation of fibrinolysis	1	1404.3×	0.001	PLAU
plasminogen activation	1	1296.3×	0.001	PLAU
fibrinolysis	1	842.6×	0.002	PLAU
positive regulation of epidermal growth factor receptor signaling pathway	1	495.6×	0.003	PLAU
regulation of cell adhesion	1	306.4×	0.005	PLAU
blood coagulation	1	173.7×	0.008	PLAU
chemotaxis	1	135.9×	0.010	PLAU
regulation of cell population proliferation	1	115.4×	0.011	PLAU
response to hypoxia	1	95.8×	0.012	PLAU
positive regulation of cell migration	1	61.7×	0.018	PLAU
proteolysis	1	34.2×	0.031	PLAU
signal transduction	1	16.1×	0.062	PLAU

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 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
PLAU	AMILORIDE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PLAU	10	4
C10orf55	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AMILORIDE HYDROCHLORIDE	4	PLAU
HEXAMIDINE	4	PLAU
MELAGATRAN	4	PLAU
AMILORIDE	4	PLAU
MILVEXIAN	3	PLAU
QUERCETIN	3	PLAU
GABEXATE	3	PLAU
SILIBININ	3	PLAU
DIBROMPROPAMIDINE	2	PLAU
UPAMOSTAT	2	PLAU

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PLAU	312	Binding:300, Functional:7, ADMET:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PLAU	3.4.21.73	u-Plasminogen activator

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PLAU	312

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

10 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)
AMILORIDE HYDROCHLORIDE	4	PLAU
HEXAMIDINE	4	PLAU
MELAGATRAN	4	PLAU
AMILORIDE	4	PLAU
MILVEXIAN	3	PLAU
QUERCETIN	3	PLAU
GABEXATE	3	PLAU
SILIBININ	3	PLAU
DIBROMPROPAMIDINE	2	PLAU
UPAMOSTAT	2	PLAU

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PLAU
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	1	C10orf55

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)
C10orf55	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.