Platelet-type bleeding disorder 11

Summary

Platelet-type bleeding disorder 11 (MONDO:0013623) is a disease caused by GP6 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: GP6 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	platelet-type bleeding disorder 11
Mondo ID	MONDO:0013623
OMIM	614201
Orphanet	98885
DOID	DOID:0111057
SNOMED CT	765977002
UMLS	C3280120
MedGen	481750
GARD	0013293
Is cancer (heuristic)	no

Also known as: BDPLT11 · bleeding disorder, platelet-type, 11 · GP6 inherited bleeding disorder, platelet-type · inherited bleeding disorder, platelet-type caused by mutation in GP6 · platelet-type bleeding disorder 11 · platelet-type bleeding disorder-11

Data availability: 20 ClinVar variants · 3 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 › platelet-type bleeding disorder 11

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 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

20 retrieved; paginated sample, class counts are floors:

12 benign, 3 pathogenic, 2 pathogenic/likely pathogenic, 1 likely benign, 1 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1072837	NM_016363.5(GP6):c.711dup (p.Val238fs)	GP6	Pathogenic	criteria provided, multiple submitters, no conflicts
1691235	NM_016363.5(GP6):c.708_711del (p.Asn236fs)	GP6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2441974	NM_016363.5(GP6):c.356_360del (p.Gln119fs)	GP6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30504	NM_016363.5(GP6):c.356_360dup (p.Gly121fs)	GP6	Pathogenic	no assertion criteria provided
30506	NM_016363.5(GP6):c.142_157del (p.Cys48fs)	GP6	Pathogenic	no assertion criteria provided
916452	NM_016363.5(GP6):c.172C>T (p.Arg58Cys)	GP6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
691634	NM_016363.5(GP6):c.584G>A (p.Ser195Asn)	GP6	Uncertain significance	criteria provided, single submitter
257411	NM_016363.5(GP6):c.*395C>T	GP6	Benign	criteria provided, multiple submitters, no conflicts
257413	NM_016363.5(GP6):c.*693A>G	GP6	Benign	criteria provided, multiple submitters, no conflicts
257416	NM_016363.5(GP6):c.*792T>C	GP6	Benign	criteria provided, multiple submitters, no conflicts
257418	NM_016363.5(GP6):c.484A>C (p.Arg162=)	GP6	Benign	criteria provided, multiple submitters, no conflicts
257419	NM_016363.5(GP6):c.495T>C (p.Phe165=)	GP6	Benign	criteria provided, multiple submitters, no conflicts
257421	NM_016363.5(GP6):c.576A>G (p.Ser192=)	GP6	Benign	criteria provided, multiple submitters, no conflicts
257422	NM_016363.5(GP6):c.655C>T (p.Pro219Ser)	GP6	Benign	criteria provided, multiple submitters, no conflicts
257423	NM_016363.5(GP6):c.709G>A (p.Glu237Lys)	GP6	Benign	criteria provided, multiple submitters, no conflicts
257424	NM_016363.5(GP6):c.745G>A (p.Ala249Thr)	GP6	Benign	criteria provided, multiple submitters, no conflicts
257426	NM_016363.5(GP6):c.936C>G (p.Leu312=)	GP6	Benign	criteria provided, multiple submitters, no conflicts
257427	NM_016363.5(GP6):c.950T>A (p.Leu317Gln)	GP6	Benign	criteria provided, multiple submitters, no conflicts
257428	NM_016363.5(GP6):c.964A>C (p.Asn322His)	GP6	Benign	criteria provided, multiple submitters, no conflicts
2690478	NM_016363.5(GP6):c.*485C>T	GP6	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
GP6	Strong	Autosomal recessive	platelet-type bleeding disorder 11	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GP6	Orphanet:98885	Bleeding diathesis due to glycoprotein VI deficiency

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
GP6	HGNC:14388	ENSG00000088053	Q9HCN6	Platelet glycoprotein VI	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GP6	Platelet glycoprotein VI	Collagen receptor involved in collagen-induced platelet adhesion and activation.

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GP6	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_fold

Expression context

Cohort genes with no expression data: 0.

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
male germ line stem cell (sensu Vertebrata) in testis	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GP6	126	tissue_specific	yes	monocyte, leukocyte, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GP6	1,416

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GP6	Q9HCN6	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Platelet Adhesion to exposed collagen	1	671.8×	0.004	GP6
GPVI-mediated activation cascade	1	308.6×	0.005	GP6
Cell surface interactions at the vascular wall	1	95.2×	0.011	GP6

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
collagen-activated signaling pathway	1	4213.0×	0.001	GP6
enzyme-linked receptor protein signaling pathway	1	1296.3×	0.001	GP6
collagen-activated tyrosine kinase receptor signaling pathway	1	1296.3×	0.001	GP6
positive regulation of platelet aggregation	1	1296.3×	0.001	GP6
immune response-regulating signaling pathway	1	455.5×	0.003	GP6
platelet aggregation	1	337.0×	0.003	GP6
platelet activation	1	267.5×	0.004	GP6

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
GP6	VALSARTAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GP6	9	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VALSARTAN	4	GP6
IBRUTINIB	4	GP6
LOSARTAN	4	GP6
ACALABRUTINIB	4	GP6
ZANUBRUTINIB	4	GP6
TIRABRUTINIB	4	GP6
EVOBRUTINIB	3	GP6
CINANSERIN	2	GP6
GAMMA-AMINOBUTYRIC ACID	1	GP6

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GP6	32	Binding:32

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

9 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)
VALSARTAN	4	GP6
IBRUTINIB	4	GP6
LOSARTAN	4	GP6
ACALABRUTINIB	4	GP6
ZANUBRUTINIB	4	GP6
TIRABRUTINIB	4	GP6
EVOBRUTINIB	3	GP6
CINANSERIN	2	GP6
GAMMA-AMINOBUTYRIC ACID	1	GP6

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GP6
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.