Platelet-type bleeding disorder 9

Summary

Platelet-type bleeding disorder 9 (MONDO:0013622) is a disease caused by ITGA2 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: ITGA2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 161

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	platelet-type bleeding disorder 9
Mondo ID	MONDO:0013622
MeSH	C566000
OMIM	614200
Orphanet	98886
DOID	DOID:0111045
UMLS	C3280114
MedGen	481744
GARD	0016868
Is cancer (heuristic)	no

Also known as: BDPLT9 · bleeding disorder, platelet-type, 9 · collagen platelet receptor deficiency · glycoprotein Ia deficiency · GP Ia deficiency

Data availability: 161 ClinVar variants · 2 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 9

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 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

161 retrieved; paginated sample, class counts are floors:

73 uncertain significance, 63 benign, 10 benign/likely benign, 8 likely benign, 7 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
353750	NM_002203.4(ITGA2):c.1189G>A (p.Gly397Ser)	ITGA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
903790	NM_004531.5(MOCS2):c.*2045G>A	ITGA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
904557	NM_002203.4(ITGA2):c.1141G>A (p.Val381Met)	ITGA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
904559	NM_002203.4(ITGA2):c.1372C>T (p.Arg458Trp)	ITGA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
905426	NM_002203.4(ITGA2):c.3034G>A (p.Asp1012Asn)	ITGA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
907936	NM_002203.4(ITGA2):c.2485C>G (p.Leu829Val)	ITGA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
907938	NM_002203.4(ITGA2):c.2608T>C (p.Ser870Pro)	ITGA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
353732	NM_002203.4(ITGA2):c.185+10T>C	ITGA2	Uncertain significance	criteria provided, single submitter
353736	NM_002203.4(ITGA2):c.614G>T (p.Gly205Val)	ITGA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
353749	NM_002203.4(ITGA2):c.1108G>A (p.Gly370Arg)	ITGA2	Uncertain significance	criteria provided, single submitter
353759	NM_002203.4(ITGA2):c.1958C>A (p.Ala653Asp)	ITGA2	Uncertain significance	criteria provided, single submitter
353760	NM_002203.4(ITGA2):c.2069A>G (p.Gln690Arg)	ITGA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
353775	NM_002203.4(ITGA2):c.2826-12A>T	ITGA2	Uncertain significance	criteria provided, single submitter
353785	NM_002203.4(ITGA2):c.*60G>A	ITGA2	Uncertain significance	criteria provided, single submitter
353786	NM_002203.4(ITGA2):c.*60G>T	ITGA2	Uncertain significance	criteria provided, single submitter
353790	NM_002203.4(ITGA2):c.*430G>C	ITGA2	Uncertain significance	criteria provided, single submitter
353794	NM_002203.4(ITGA2):c.*609T>G	ITGA2	Uncertain significance	criteria provided, single submitter
353795	NM_002203.4(ITGA2):c.*613C>T	ITGA2	Uncertain significance	criteria provided, single submitter
353799	NM_002203.4(ITGA2):c.*859T>C	ITGA2	Uncertain significance	criteria provided, single submitter
353802	NM_002203.4(ITGA2):c.*1199C>T	ITGA2	Uncertain significance	criteria provided, single submitter
353804	NM_002203.4(ITGA2):c.*1322T>C	ITGA2	Uncertain significance	criteria provided, single submitter
353807	NM_002203.4(ITGA2):c.*1671G>C	ITGA2	Uncertain significance	criteria provided, single submitter
353813	NM_002203.4(ITGA2):c.*1947T>C	ITGA2	Uncertain significance	criteria provided, single submitter
353817	NM_002203.4(ITGA2):c.*2089G>C	ITGA2	Uncertain significance	criteria provided, single submitter
353821	NM_002203.4(ITGA2):c.*2392G>A	ITGA2	Uncertain significance	criteria provided, single submitter
353822	NM_002203.4(ITGA2):c.*2429C>T	ITGA2	Uncertain significance	criteria provided, single submitter
353823	NM_002203.4(ITGA2):c.*2450G>A	ITGA2	Uncertain significance	criteria provided, single submitter
353830	NM_002203.4(ITGA2):c.*2608A>G	ITGA2	Uncertain significance	criteria provided, single submitter
353831	NM_002203.4(ITGA2):c.*2653T>G	ITGA2	Uncertain significance	criteria provided, single submitter
353832	NM_002203.4(ITGA2):c.*2674G>C	ITGA2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
ITGA2	Strong	Autosomal dominant	platelet-type bleeding disorder 9	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ITGA2	Orphanet:853	Fetal and neonatal alloimmune thrombocytopenia

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
ITGA2	HGNC:6137	ENSG00000164171	P17301	Integrin alpha-2	gencc,clinvar
ITGA2-AS1	HGNC:40306	ENSG00000249899		ITGA2 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ITGA2	Integrin alpha-2	Integrin alpha-2/beta-1 is a receptor for laminin, collagen, collagen C-propeptides, fibronectin and E-cadherin.

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
Antibody/Immunoglobulin	1	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ITGA2	Antibody/Immunoglobulin	yes		Integrin_alpha, VWF_A, FG-GAP
ITGA2-AS1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
epithelium of nasopharynx	1
nasopharynx	1
ventricular zone	1
calcaneal tendon	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ITGA2	240	ubiquitous	marker	ventricular zone, epithelium of nasopharynx, nasopharynx
ITGA2-AS1	129		yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITGA2	2,578
ITGA2-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ITGA2	P17301	17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 21. 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
CHL1 interactions	1	1268.9×	0.008	ITGA2
Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition	1	878.5×	0.008	ITGA2
Platelet Adhesion to exposed collagen	1	671.8×	0.008	ITGA2
MET promotes cell motility	1	601.0×	0.008	ITGA2
Syndecan interactions	1	423.0×	0.008	ITGA2
Laminin interactions	1	380.7×	0.008	ITGA2
MET activates PTK2 signaling	1	380.7×	0.008	ITGA2
Signaling by MET	1	317.2×	0.008	ITGA2
MITF-M-dependent gene expression	1	181.3×	0.013	ITGA2
Non-integrin membrane-ECM interactions	1	154.3×	0.013	ITGA2
ECM proteoglycans	1	150.3×	0.013	ITGA2
Integrin cell surface interactions	1	134.3×	0.013	ITGA2
L1CAM interactions	1	120.2×	0.013	ITGA2
MITF-M-regulated melanocyte development	1	114.2×	0.013	ITGA2
Extracellular matrix organization	1	63.1×	0.022	ITGA2
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.025	ITGA2
Axon guidance	1	45.1×	0.027	ITGA2
Nervous system development	1	42.9×	0.027	ITGA2
Hemostasis	1	36.0×	0.031	ITGA2
Developmental Biology	1	14.5×	0.073	ITGA2
Signal Transduction	1	10.2×	0.098	ITGA2

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
hypotonic response	1	8426.0×	0.002	ITGA2
response to L-ascorbic acid	1	4213.0×	0.002	ITGA2
collagen-activated signaling pathway	1	4213.0×	0.002	ITGA2
response to parathyroid hormone	1	4213.0×	0.002	ITGA2
positive regulation of cell projection organization	1	3370.4×	0.002	ITGA2
substrate-dependent cell migration	1	2407.4×	0.002	ITGA2
positive regulation of transmission of nerve impulse	1	2407.4×	0.002	ITGA2
response to amine	1	1872.4×	0.002	ITGA2
mesodermal cell differentiation	1	1532.0×	0.002	ITGA2
skin morphogenesis	1	1404.3×	0.002	ITGA2
positive regulation of positive chemotaxis	1	1404.3×	0.002	ITGA2
positive regulation of phagocytosis, engulfment	1	1296.3×	0.002	ITGA2
hepatocyte differentiation	1	1203.7×	0.002	ITGA2
detection of mechanical stimulus involved in sensory perception of pain	1	1123.5×	0.002	ITGA2
positive regulation of leukocyte migration	1	991.3×	0.002	ITGA2
positive regulation of smooth muscle cell migration	1	991.3×	0.002	ITGA2
positive regulation of smooth muscle contraction	1	936.2×	0.002	ITGA2
cell-substrate adhesion	1	766.0×	0.003	ITGA2
cell adhesion mediated by integrin	1	674.1×	0.003	ITGA2
mammary gland development	1	648.1×	0.003	ITGA2
positive regulation of collagen biosynthetic process	1	648.1×	0.003	ITGA2
response to muscle activity	1	581.1×	0.003	ITGA2
focal adhesion assembly	1	526.6×	0.003	ITGA2
positive regulation of epithelial cell migration	1	411.0×	0.004	ITGA2
cellular response to estradiol stimulus	1	411.0×	0.004	ITGA2
positive regulation of smooth muscle cell proliferation	1	330.4×	0.005	ITGA2
positive regulation of cell adhesion	1	271.8×	0.005	ITGA2
positive regulation of translation	1	227.7×	0.006	ITGA2
cellular response to mechanical stimulus	1	216.1×	0.006	ITGA2
female pregnancy	1	210.7×	0.006	ITGA2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ITGA2	0	0
ITGA2-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ITGA2	21	Binding:20, Functional:1

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	ITGA2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ITGA2-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ITGA2	21	—
ITGA2-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.