Bernard-Soulier syndrome, type A2, autosomal dominant

Summary

Bernard-Soulier syndrome, type A2, autosomal dominant (MONDO:0007930) is a disease caused by GP1BA (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: GP1BA (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 50

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bernard-Soulier syndrome, type A2, autosomal dominant
Mondo ID	MONDO:0007930
OMIM	153670
DOID	DOID:0111059
UMLS	C3277076
MedGen	478706
GARD	0015082
Is cancer (heuristic)	no

Also known as: Bernard-Soulier syndrome, type A2 (dominant) · Bernard-Soulier syndrome, type A2, autosomal dominant · BSSA2

Data availability: 50 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 › Bernard-Soulier syndrome › Bernard-Soulier syndrome, type A2, autosomal dominant

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

50 retrieved; paginated sample, class counts are floors:

18 likely pathogenic, 17 uncertain significance, 7 pathogenic, 3 benign, 2 pathogenic/likely pathogenic, 1 likely benign, 1 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1677261	NM_000173.7(GP1BA):c.58T>G (p.Cys20Gly)	GP1BA	Pathogenic	criteria provided, multiple submitters, no conflicts
1691251	NM_000173.7(GP1BA):c.1480del (p.Thr494fs)	GP1BA	Pathogenic	reviewed by expert panel
1695379	NM_000173.7(GP1BA):c.97T>C (p.Cys33Arg)	GP1BA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4156	NM_000173.7(GP1BA):c.515C>T (p.Ala172Val)	GP1BA	Pathogenic	criteria provided, multiple submitters, no conflicts
4157	NM_000173.7(GP1BA):c.1620G>A (p.Trp540Ter)	GP1BA	Pathogenic	reviewed by expert panel
435347	NM_000173.7(GP1BA):c.673T>A (p.Cys225Ser)	GP1BA	Pathogenic	reviewed by expert panel
626958	NM_000173.7(GP1BA):c.344T>C (p.Leu115Pro)	GP1BA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
872581	NM_000173.7(GP1BA):c.1601_1602del (p.Tyr534fs)	GP1BA	Pathogenic	reviewed by expert panel
988865	NM_000173.7(GP1BA):c.1274_1275del (p.Glu425fs)	GP1BA	Pathogenic	criteria provided, single submitter
1676741	NM_000173.7(GP1BA):c.169A>G (p.Asn57Asp)	GP1BA	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1677265	NM_000173.7(GP1BA):c.247C>T (p.Leu83Phe)	GP1BA	Likely pathogenic	criteria provided, single submitter
1684365	NM_000173.7(GP1BA):c.434T>C (p.Leu145Pro)	GP1BA	Likely pathogenic	reviewed by expert panel
1684403	NM_000173.7(GP1BA):c.98G>A (p.Cys33Tyr)	GP1BA	Likely pathogenic	no assertion criteria provided
3251584	NM_000173.7(GP1BA):c.987G>A (p.Trp329Ter)	GP1BA	Likely pathogenic	reviewed by expert panel
3582320	NM_000173.7(GP1BA):c.70A>T (p.Lys24Ter)	GP1BA	Likely pathogenic	criteria provided, single submitter
3582321	NM_000173.7(GP1BA):c.298del (p.Leu100fs)	GP1BA	Likely pathogenic	criteria provided, single submitter
3582323	NM_000173.7(GP1BA):c.624del (p.Phe208fs)	GP1BA	Likely pathogenic	reviewed by expert panel
3582324	NM_000173.7(GP1BA):c.783dup (p.Val262fs)	GP1BA	Likely pathogenic	criteria provided, single submitter
3582326	NM_000173.7(GP1BA):c.883del (p.Tyr295fs)	GP1BA	Likely pathogenic	criteria provided, single submitter
3582327	NM_000173.7(GP1BA):c.1009C>T (p.Gln337Ter)	GP1BA	Likely pathogenic	criteria provided, single submitter
3582329	NM_000173.7(GP1BA):c.1426del (p.Ser476fs)	GP1BA	Likely pathogenic	criteria provided, single submitter
3582330	NM_000173.7(GP1BA):c.1436T>A (p.Leu479Ter)	GP1BA	Likely pathogenic	criteria provided, single submitter
3582331	NM_000173.7(GP1BA):c.1699C>T (p.Gln567Ter)	GP1BA	Likely pathogenic	criteria provided, single submitter
3731495	NM_000173.7(GP1BA):c.969G>A (p.Trp323Ter)	GP1BA	Likely pathogenic	criteria provided, single submitter
4086242	NM_000173.7(GP1BA):c.464T>C (p.Leu155Pro)	GP1BA	Likely pathogenic	criteria provided, single submitter
4154	NM_000173.7(GP1BA):c.217C>T (p.Leu73Phe)	GP1BA	Likely pathogenic	criteria provided, multiple submitters, no conflicts
627076	NM_000173.7(GP1BA):c.449A>G (p.Asn150Ser)	GP1BA	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1679418	NM_000173.7(GP1BA):c.137C>T (p.Pro46Leu)	GP1BA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1677264	NM_000173.7(GP1BA):c.463C>G (p.Leu155Val)	GP1BA	Uncertain significance	reviewed by expert panel
1684363	NM_000173.7(GP1BA):c.191T>C (p.Leu64Pro)	GP1BA	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 4 · 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
GP1BA	Definitive	Autosomal recessive	Bernard-Soulier syndrome	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GP1BA	Orphanet:140957	Autosomal dominant macrothrombocytopenia
GP1BA	Orphanet:274	Bernard-Soulier syndrome
GP1BA	Orphanet:52530	Pseudo-von Willebrand disease
GP1BA	Orphanet:853	Fetal and neonatal alloimmune thrombocytopenia

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
GP1BA	HGNC:4439	ENSG00000185245	P07359	Platelet glycoprotein Ib alpha chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GP1BA	Platelet glycoprotein Ib alpha chain	GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium.

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)
GP1BA	Other/Unknown	no		LRRNT, Cys-rich_flank_reg_C, Leu-rich_rpt

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
GP1BA	186	tissue_specific	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GP1BA	1,703

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GP1BA	P07359	22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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 F9 activation	1	1903.3×	0.002	GP1BA
Enhanced binding of GP1BA variant to VWF multimer:collagen	1	1631.4×	0.002	GP1BA
Defective binding of VWF variant to GPIb:IX:V	1	1631.4×	0.002	GP1BA
FXIIa, PKa-dependent activation of coagulation pathway	1	1142.0×	0.002	GP1BA
GP1b-IX-V activation signalling	1	951.7×	0.002	GP1BA
Platelet Adhesion to exposed collagen	1	671.8×	0.002	GP1BA
Amplification and propagation of coagulation cascade	1	634.4×	0.002	GP1BA
Platelet Aggregation (Plug Formation)	1	439.2×	0.003	GP1BA
Regulation of clotting cascade	1	233.1×	0.005	GP1BA
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1	120.2×	0.008	GP1BA

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
blood coagulation, intrinsic pathway	1	2106.5×	0.003	GP1BA
regulation of blood coagulation	1	1872.4×	0.003	GP1BA
positive regulation of platelet activation	1	1296.3×	0.003	GP1BA
fibrinolysis	1	842.6×	0.003	GP1BA
megakaryocyte development	1	702.2×	0.003	GP1BA
release of sequestered calcium ion into cytosol	1	343.9×	0.005	GP1BA
platelet activation	1	267.5×	0.006	GP1BA
blood coagulation	1	173.7×	0.008	GP1BA
cell morphogenesis	1	157.5×	0.008	GP1BA
cell surface receptor signaling pathway	1	64.1×	0.017	GP1BA
cell adhesion	1	37.5×	0.027	GP1BA

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GP1BA	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	GP1BA

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)
GP1BA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.