GP9

Summary

GP9 (glycoprotein IX platelet, HGNC:4444) is a protein-coding gene on chromosome 3q21.3, encoding Platelet glycoprotein IX (P14770). The GPIb-V-IX complex functions as the vWF receptor and mediates vWF-dependent platelet adhesion to blood vessels.

This gene encodes a small membrane glycoprotein found on the surface of human platelets. It forms a 1-to-1 noncovalent complex with glycoprotein Ib, a platelet surface membrane glycoprotein complex that functions as a receptor for von Willebrand factor. The complete receptor complex includes noncovalent association of the alpha and beta subunits with the protein encoded by this gene and platelet glycoprotein V. Defects in this gene are a cause of Bernard-Soulier syndrome, also known as giant platelet disease. These patients have unusually large platelets and have a clinical bleeding tendency.

Source: NCBI Gene 2815 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Bernard-Soulier syndrome (Definitive, ClinGen)
• GWAS associations: 4
• Clinical variants (ClinVar): 171 total — 11 pathogenic, 18 likely-pathogenic
• Phenotypes (HPO): 27
• MANE Select transcript: NM_000174

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4444
Approved symbol	GP9
Name	glycoprotein IX platelet
Location	3q21.3
Locus type	gene with protein product
Status	Approved
Aliases	CD42a, GPIX
Ensembl gene	ENSG00000169704
Ensembl biotype	protein_coding
OMIM	173515
Entrez	2815

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000307395, ENST00000900754, ENST00000900755, ENST00000900756, ENST00000900757, ENST00000954980

RefSeq mRNA: 1 — MANE Select: NM_000174 NM_000174

CCDS: CCDS3055

Canonical transcript exons

ENST00000307395 — 3 exons

Exon	Start	End
ENSE00001127426	129061728	129062406
ENSE00001177124	129061494	129061619
ENSE00001177133	129060779	129060850

Expression profiles

Bgee: expression breadth broad, 88 present calls, max score 96.45.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.2246 / max 445.7813, expressed in 97 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38501	2.1345	91
202925	0.0901	27

Top tissues by expression

240 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	96.45	gold quality
mononuclear cell	CL:0000842	96.16	gold quality
leukocyte	CL:0000738	95.24	gold quality
granulocyte	CL:0000094	87.31	gold quality
buccal mucosa cell	CL:0002336	84.17	gold quality
triceps brachii	UBERON:0001509	83.93	gold quality
blood	UBERON:0000178	83.28	gold quality
gluteal muscle	UBERON:0002000	83.21	gold quality
parotid gland	UBERON:0001831	79.21	gold quality
right lung	UBERON:0002167	73.34	gold quality
spleen	UBERON:0002106	73.13	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	72.62	gold quality
trabecular bone tissue	UBERON:0002483	71.15	gold quality
bone marrow	UBERON:0002371	69.34	gold quality
biceps brachii	UBERON:0001507	68.27	gold quality
periodontal ligament	UBERON:0008266	67.46	silver quality
deltoid	UBERON:0001476	64.47	gold quality
heart right ventricle	UBERON:0002080	63.79	gold quality
upper lobe of left lung	UBERON:0008952	62.51	gold quality
bone marrow cell	CL:0002092	61.53	silver quality
myocardium	UBERON:0002349	61.16	gold quality
nasal cavity mucosa	UBERON:0001826	61.03	gold quality
upper lobe of lung	UBERON:0008948	60.36	gold quality
epithelium of bronchus	UBERON:0002031	59.91	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	59.60	gold quality
quadriceps femoris	UBERON:0001377	59.28	gold quality
bronchial epithelial cell	CL:0002328	59.21	gold quality
bronchus	UBERON:0002185	59.20	gold quality
pleura	UBERON:0000977	58.79	gold quality
nasal cavity epithelium	UBERON:0005384	58.57	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-GEOD-149689	yes	3754.19
E-MTAB-6701	yes	3019.58
E-HCAD-10	yes	2705.60
E-CURD-112	yes	2513.68
E-MTAB-7407	yes	1507.66
E-MTAB-9067	yes	709.71
E-HCAD-4	yes	53.40
E-CURD-122	yes	25.18
E-MTAB-9221	yes	24.27
E-HCAD-1	yes	9.45
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1, FLI1, GATA1, KLF1, ZBTB16

miRNA regulators (miRDB)

7 targeting GP9, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-590-5P	99.25	70.76	930
HSA-MIR-1911-3P	99.15	66.17	528
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-558	97.50	67.16	977

Literature-anchored findings (GeneRIF, showing 31)

• Both the high affinity thrombin receptor (GPIb-IX-V) and GPIIb/IIIa are implicated in expression of thrombin-induced platelet procoagulant activity. (PMID:11686325)
• Lateral clustering of platelet GP Ib-IX complexes leads to up-regulation of the adhesive function of integrin alpha IIbbeta 3 (PMID:11812775)
• The cysteine knot of platelet GPIb beta is critical for the interaction of GPIb beta with GPIX. (PMID:12036872)
• PKA-mediated phosphorylation of GPIbbeta at Ser(166) negatively regulates VWF binding to GPIb-IX and is one of the mechanisms by which PKA mediates platelet inhibition (PMID:12361948)
• Novel nonsense mutation is associated with Bernard-Soulier syndrome. (PMID:12447957)
• structure-activity relationship of mutations found in Bernard-Soulier syndrome (PMID:12463594)
• factor XI is localized to GPIb in membrane rafts and this association is important for promoting the activation of factor XI by thrombin on the platelet surface (PMID:12517745)
• findings indicate that the Ala14–>Thr mutation in the transmembrane region of GP IX does not induce intracellular GP Ib/IX complex degradation, but prevents its insertion in the cytoplasmic membrane of platelets and CHO cells (PMID:15351858)
• 3 families from Iran with Bernard-Soulier syndrome were investigated; the presence of the same GpIX Phe55Ser missense mutation in two families and of a single base insertion (GP1BA C3221 ins) in the third family were demonstrated (PMID:17763149)
• the first non-Caucasian Turkish Bernard-Soulier syndrome case due to GPIX N45S and is likely the result of a recurrent mutational event. (PMID:17804902)
• The transmembrane domain of GPIX plays an important role in expression and assembly of the GPIb-IX complex by interacting with its counterparts of GPIb. (PMID:17922811)
• Polymorphisms in human platelet alloantigen (HPA)-1 and HPA-3 (GPIIb/IIIa), HPA-2 (GPIb/IX), HPA-4 (GPIIIa) and HPA-5 (GPIa/IIa) were found to be associated with the symptoms and recurrence of ischemic stroke. (PMID:18057877)
• laminin supports platelet adhesion depending on the interaction of VWF and GPIb-IX-V under pathophysiological high shear flow (PMID:18450753)
• glycoprotein Ib-IX-V complex contributes to tissue factor-independent thrombin generation by recombinant factor VIIa on the activated platelet surface (PMID:18612104)
• Data demonstrate the native-like heteromeric interaction among the isolated Ibalpha, Ib beta and IX TM peptides, which provides support for the four-helix bundle model of the TM domains in the glycoprotein Ib-IX complex. (PMID:18674540)
• Findings point to a role of the GPIb-V-IX complex intrinsic to megakaryocytes at the stage of proplatelet formation and suggest a functional link with the underlying microtubular cytoskeleton in platelet biogenesis. (PMID:19377075)
• Homozygous missense mutation in position 1829 (A(R)G) of the GPIX gene causes Bernard-Soulier syndrome in a Swiss family. (PMID:19404517)
• 14-3-3beta, 14-3-3gamma, 14-3-3epsilon, 14-3-3eta and 14-3-3theta isoforms interact with the GPIb-IX complex in platelets (PMID:19558434)
• the putative convex surface of the LRR domain in GPIX is sufficient, in the context of full-length subunit, to mediate its association with GPIbbeta (PMID:19566547)
• Raft association and cytoskeletal linkage of the platelet GPIb-IX-V complex are interrelated and are required for optimal receptor function, by attracting signaling proteins and membrane skeletal association allows proteins to move to new locations. (PMID:19874464)
• GP Ibbeta/GP IX mediates the disulfide-linked GP Ibalpha localization to the GEMs, which is critical for vWf interaction at high shear (PMID:21507943)
• GPIIb/IIIa is the primary receptor set involved in platelet adhesion to adsorbed fibrinogen and serum albumin irrespective of their degree of adsorption-induced unfolding, while the GPIb-IX-V receptor complex plays an insignificant role. (PMID:21529934)
• Report glycoprotein Ib/IX complex mutations found in Bernard-Soulier syndrome in Indian patients. (PMID:21699652)
• GPIbbeta missense mutations from Bernard-Soulier syndrome were examined for changes to GPIb-IX complex surface expression. Mutations A108P and P74R were found to maintain normal secretion/folding of GPIbbeta(E) but were unable to support GPIX surface expression (PMID:21908432)
• GPIX increased the expression of GPIba by promoting the formation of a disulfide bond between GPIba and GPIbb in transfected CHO-K1 cells. (PMID:23143686)
• Studies indicate that platelets from Bernard-Soulier syndrome (BSS) are defective in glycoprotein (GP)Ib-IX-V, a platelet-specific adhesion-signaling complex, composed of GPIbalpha disulfide linked to GPIbbeta, and noncovalently associated with GPIX and GPV. (PMID:23929303)
• genetic association study in population in western India: Data suggest novel mutations in platelet glycoprotein Ib (GP1BA, GP1BB) and GP9 are associated with Bernard-Soulier syndrome in subjects studies; of 12 mutations identified, ten were novel. (PMID:23995613)
• Data show that localization of the GP Ib-IX complex to the lipid domain is mediated by GP Ibbeta and GP IX transmembrane domains. (PMID:26203189)
• Case Report: suggest that alloantibodies directed against Cab4b, the first human platelet antigen carried by glycoprotein IX, can induce severe neonatal thrombocytopenia. (PMID:28561420)
• ERK5 associates with CKII to play essential roles in GPIb-IX-mediated platelet activation via the PTEN/PI3K/Akt pathway. (PMID:28603902)
• Oxidation shuts down an auto-inhibitory mechanism of von Willebrand factor. (PMID:33550613)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gp9	ENSDARG00000090638
mus_musculus	Gp9	ENSMUSG00000030054
rattus_norvegicus	Gp9	ENSRNOG00000010015

Paralogs (1): GP1BB (ENSG00000203618)

Protein

Protein identifiers

Platelet glycoprotein IX — P14770 (reviewed: P14770)

Alternative names: Glycoprotein 9

All UniProt accessions (1): P14770

UniProt curated annotations — full annotation on UniProt →

Function. The GPIb-V-IX complex functions as the vWF receptor and mediates vWF-dependent platelet adhesion to blood vessels. The adhesion of platelets to injured vascular surfaces in the arterial circulation is a critical initiating event in hemostasis. GP-IX may provide for membrane insertion and orientation of GP-Ib.

Subunit / interactions. Two GP-Ib beta are disulfide-linked to one GP-Ib alpha. GP-IX is complexed with the GP-Ib heterodimer via a non covalent linkage.

Subcellular location. Membrane.

Disease relevance. Bernard-Soulier syndrome (BSS) [MIM:231200] An autosomal recessive coagulation disorder characterized by a prolonged bleeding time, unusually large platelets, thrombocytopenia, and impaired prothrombin consumption. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Platelet activation apparently involves disruption of the macromolecular complex of GP-Ib with the platelet glycoprotein IX (GP-IX) and dissociation of GP-Ib from the actin-binding protein.

RefSeq proteins (1): NP_000165* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000372	LRRNT	Domain
IPR000483	Cys-rich_flank_reg_C	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR052313	GPIb-IX-V_Complex	Family

Pfam: PF01462, PF13855

UniProt features (32 total): sequence variant 8, strand 5, turn 4, helix 4, sequence conflict 2, topological domain 2, domain 2, signal peptide 1, chain 1, transmembrane region 1, repeat 1, glycosylation site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3REZ	X-RAY DIFFRACTION	2.35
8WFS	ELECTRON MICROSCOPY	3.36

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14770-F1	84.43	0.61

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 60

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-430116	GP1b-IX-V activation signalling
R-HSA-75892	Platelet Adhesion to exposed collagen
R-HSA-76009	Platelet Aggregation (Plug Formation)
R-HSA-9673221	Defective F9 activation
R-HSA-9769739	Regulation of clotting cascade
R-HSA-9769743	Amplification and propagation of coagulation cascade
R-HSA-9845620	Enhanced binding of GP1BA variant to VWF multimer:collagen
R-HSA-9846298	Defective binding of VWF variant to GPIb:IX:V
R-HSA-9935598	FXIIa, PKa-dependent activation of coagulation pathway
R-HSA-140837

MSigDB gene sets: 205 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_PROTEIN_ACTIVATION_CASCADE, GOBP_MYELOID_CELL_DEVELOPMENT, REACTOME_PLATELET_AGGREGATION_PLUG_FORMATION, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_PLATELET_ACTIVATION, MODULE_64, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_WOUND_HEALING, GOBP_PROTEIN_MATURATION, GOBP_MAINTENANCE_OF_LOCATION, GOBP_BLOOD_COAGULATION_INTRINSIC_PATHWAY, GOBP_POSITIVE_REGULATION_OF_CELL_ACTIVATION, GOBP_MEGAKARYOCYTE_DEVELOPMENT

GO Biological Process (7): cell adhesion (GO:0007155), blood coagulation (GO:0007596), blood coagulation, intrinsic pathway (GO:0007597), positive regulation of platelet activation (GO:0010572), megakaryocyte development (GO:0035855), release of sequestered calcium ion into cytosol (GO:0051209), hemostasis (GO:0007599)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), glycoprotein Ib-IX-V complex (GO:1990779), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Platelet activation, signaling and aggregation	2
Coagulation pathway	2
Defects of platelet adhesion to exposed collagen	2
Hemostasis	1
Defective factor IX causes hemophilia B	1
Regulation of clotting cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
hemostasis	1
wound healing	1
coagulation	1
protein activation cascade	1
blood coagulation, fibrin clot formation	1
regulation of platelet activation	1
platelet activation	1
positive regulation of cell activation	1
megakaryocyte differentiation	1
myeloid cell development	1
intercellular transport	1
calcium ion transmembrane import into cytosol	1
regulation of body fluid levels	1
binding	1
membrane	1
cell periphery	1
glycoprotein complex	1
plasma membrane signaling receptor complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1214 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GP9	GP1BA	P07359	999
GP9	GP5	P40197	997
GP9	GP1BB	P13224	986
GP9	VWF	P04275	977
GP9	GTPBP1	O00178	918
GP9	ITGA2B	P08514	914
GP9	CD36	P16671	854
GP9	ITGB3	P05106	817
GP9	GP6	Q9HCN6	796
GP9	SELP	P16109	720
GP9	S100A10	P08206	672
GP9	GP2	P55259	651
GP9	F8	P00451	591
GP9	SCARB2	Q14108	589
GP9	SCARB1	Q8WTV0	580

IntAct

24 interactions, top by confidence:

A	B	Type	Score
GP9	GP1BA	psi-mi:“MI:0914”(association)	0.790
GP1BA	GP9	psi-mi:“MI:2364”(proximity)	0.790
GP1BA	GP1BB	psi-mi:“MI:0915”(physical association)	0.700
GP9	HOXA1	psi-mi:“MI:0915”(physical association)	0.670
HOXA1	GP9	psi-mi:“MI:0915”(physical association)	0.670
GP9	SPRY2	psi-mi:“MI:0915”(physical association)	0.560
SPRY2	GP9	psi-mi:“MI:0915”(physical association)	0.560
GP5	GP9	psi-mi:“MI:0915”(physical association)	0.500
GP9	APPBP2	psi-mi:“MI:0915”(physical association)	0.490
GP9	CRK	psi-mi:“MI:0915”(physical association)	0.400
GP9	Hoxa1	psi-mi:“MI:0915”(physical association)	0.370
GP9	TNFSF14	psi-mi:“MI:0914”(association)	0.350
NUDT1	TNFSF14	psi-mi:“MI:0914”(association)	0.350
GP9	ESYT2	psi-mi:“MI:0914”(association)	0.350
NUDT1	GP9	psi-mi:“MI:0914”(association)	0.350

BioGRID (93): HOXA1 (Two-hybrid), SPRY2 (Two-hybrid), HOXA1 (Two-hybrid), GP9 (Affinity Capture-Western), GP9 (Affinity Capture-RNA), TNFSF14 (Affinity Capture-MS), LEMD3 (Affinity Capture-MS), LRRC8A (Affinity Capture-MS), FAM69A (Affinity Capture-MS), GLRB (Affinity Capture-MS), FZD6 (Affinity Capture-MS), ATP13A2 (Affinity Capture-MS), CTAGE5 (Affinity Capture-MS), DPY19L4 (Affinity Capture-MS), GP9 (Affinity Capture-MS)

ESM2 similar proteins: A1A4H9, A2VDH3, A3KNN3, A6H789, A6H793, A8WHP9, O14498, O75325, O88186, P14770, P59034, P59035, Q13641, Q149C3, Q2EEY0, Q3UVD5, Q3UY51, Q4KLL3, Q4R8Y9, Q5I2M3, Q5I2M4, Q5I2M5, Q5I2M7, Q5I2M8, Q5NVQ6, Q5PQV5, Q5VT99, Q6UY18, Q6ZSA7, Q7M6Z0, Q80WD0, Q80WD1, Q80ZD7, Q86UN2, Q86UN3, Q86WK6, Q86WK7, Q8BHA1, Q8C2S7, Q8K0S5

Diamond homologs: A2AJ76, A4IFA6, A6NJW4, A8WHP9, O14498, P14770, P59034, P59035, Q13641, Q15109, Q28173, Q4R8Y9, Q5NVQ6, Q5RKR3, Q62151, Q63495, Q6GU68, Q6UXK2, Q6WRH9, Q96RW7, A3KNN3, A4IIW9, A6H789, A6H793, C3YZ59, E5DHB5, G5EFX6, O02678, O35367, O42235, O46542, O60938, O62702, O75093, O75094, O88186, O88279, O88280, O94813, P02750

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
FLI1	“up-regulates quantity by expression”	GP9	“transcriptional regulation”
GATA1	“up-regulates quantity by expression”	GP9	“transcriptional regulation”
GP9	“form complex”	“GPIb-IX-V complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

171 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	18
Uncertain significance	59
Likely benign	63
Benign	10

Top pathogenic / likely-pathogenic (29)

Variant ID	HGVS	Classification
1333009	NC_000003.12:g.129058767_129062425del	Pathogenic
1338739	NM_000174.5(GP9):c.-210_*133del (p.Met1fs)	Pathogenic
13529	NM_000174.5(GP9):c.182A>G (p.Asn61Ser)	Pathogenic
13530	NM_000174.5(GP9):c.110A>G (p.Asp37Gly)	Pathogenic
13531	NM_000174.5(GP9):c.212T>C (p.Phe71Ser)	Pathogenic
2190152	NM_000174.5(GP9):c.2T>C (p.Met1Thr)	Pathogenic
2573379	NM_000174.5(GP9):c.8_11dup (p.Trp4fs)	Pathogenic
3366941	NM_000174.5(GP9):c.46dup (p.Ala16fs)	Pathogenic
3644914	NM_000174.5(GP9):c.34del (p.Ala12fs)	Pathogenic
3775050	NM_000174.5(GP9):c.266G>A (p.Cys89Tyr)	Pathogenic
662842	NC_000003.12:g.(?129061730)(129062283_?)del	Pathogenic
13532	NM_000174.5(GP9):c.167T>C (p.Leu56Pro)	Likely pathogenic
13533	NM_000174.5(GP9):c.70T>C (p.Cys24Arg)	Likely pathogenic
13534	NM_000174.5(GP9):c.20T>C (p.Leu7Pro)	Likely pathogenic
1491487	NM_000174.5(GP9):c.212T>G (p.Phe71Cys)	Likely pathogenic
2503424	NM_000174.5(GP9):c.429G>A (p.Trp143Ter)	Likely pathogenic
2503896	NM_000174.5(GP9):c.284A>G (p.Tyr95Cys)	Likely pathogenic
2734558	NM_000174.5(GP9):c.119del (p.Gly40fs)	Likely pathogenic
3588369	NM_000174.5(GP9):c.70_74delinsGTGGG (p.Cys24_Thr25delinsValGly)	Likely pathogenic
3588370	NM_000174.5(GP9):c.261G>A (p.Trp87Ter)	Likely pathogenic
3588371	NM_000174.5(GP9):c.342_361dup (p.His121fs)	Likely pathogenic
3588372	NM_000174.5(GP9):c.442dup (p.Val148fs)	Likely pathogenic
3775051	NM_000174.5(GP9):c.305_313del (p.Asp102_Pro105delinsAla)	Likely pathogenic
4088263	NM_000174.5(GP9):c.450G>A (p.Trp150Ter)	Likely pathogenic
4088264	NM_000174.5(GP9):c.437_474dup (p.Ala159fs)	Likely pathogenic
4539008	NM_000174.5(GP9):c.285T>G (p.Tyr95Ter)	Likely pathogenic
4539010	NM_000174.5(GP9):c.112T>C (p.Cys38Arg)	Likely pathogenic
4687494	NM_000174.5(GP9):c.404G>A (p.Cys135Tyr)	Likely pathogenic
623661	NM_000174.5(GP9):c.337del (p.Cys113fs)	Likely pathogenic

SpliceAI

376 predictions. Top by Δscore:

Variant	Effect	Δscore
3:129060847:ACAGG:A	donor_loss	0.9800
3:129060848:CAGGT:C	donor_loss	0.9800
3:129060849:AGG:A	donor_loss	0.9800
3:129060851:G:T	donor_loss	0.9800
3:129060852:T:G	donor_loss	0.9800
3:129061727:GCCA:G	acceptor_gain	0.9800
3:129061888:C:A	acceptor_gain	0.9800
3:129060851:G:GG	donor_gain	0.9700
3:129061726:A:AG	acceptor_gain	0.9700
3:129061727:G:GG	acceptor_gain	0.9700
3:129061727:GCC:G	acceptor_gain	0.9700
3:129060848:CAG:C	donor_gain	0.9600
3:129061492:A:AG	acceptor_gain	0.9500
3:129061493:G:GG	acceptor_gain	0.9500
3:129061727:GC:G	acceptor_gain	0.9500
3:129060851:GTA:G	donor_gain	0.9400
3:129061722:CTGCA:C	acceptor_loss	0.9300
3:129061723:TGCA:T	acceptor_loss	0.9300
3:129061724:GCAG:G	acceptor_loss	0.9300
3:129061725:CA:C	acceptor_loss	0.9300
3:129060849:AG:A	donor_gain	0.9200
3:129060850:GG:G	donor_gain	0.9200
3:129061493:GCCGC:G	acceptor_gain	0.9100
3:129061493:GCC:G	acceptor_gain	0.9000
3:129060852:T:TC	donor_gain	0.8900
3:129061615:GGGAG:G	donor_gain	0.8900
3:129061616:GGAGG:G	donor_gain	0.8900
3:129061715:CCTCT:C	acceptor_loss	0.8800
3:129061716:CTCTC:C	acceptor_loss	0.8800
3:129061717:TCTCT:T	acceptor_loss	0.8800

AlphaMissense

1110 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:129062000:G:C	W87C	0.994
3:129062000:G:T	W87C	0.994
3:129061922:C:A	N61K	0.989
3:129061922:C:G	N61K	0.989
3:129062036:G:C	W99C	0.988
3:129062036:G:T	W99C	0.988
3:129061994:C:A	N85K	0.987
3:129061994:C:G	N85K	0.987
3:129061998:T:A	W87R	0.986
3:129061998:T:C	W87R	0.986
3:129061992:A:T	N85Y	0.983
3:129061921:A:T	N61I	0.979
3:129062005:G:A	C89Y	0.979
3:129061951:T:G	F71C	0.977
3:129061992:A:G	N85D	0.977
3:129062004:T:A	C89S	0.975
3:129062005:G:C	C89S	0.975
3:129061920:A:T	N61Y	0.973
3:129061951:T:C	F71S	0.972
3:129062076:T:A	C113S	0.968
3:129062077:G:C	C113S	0.968
3:129061906:T:A	L56H	0.966
3:129061851:T:A	C38S	0.964
3:129061852:G:C	C38S	0.964
3:129061993:A:C	N85T	0.964
3:129061852:G:A	C38Y	0.962
3:129062005:G:T	C89F	0.962
3:129062150:G:C	W137C	0.962
3:129062150:G:T	W137C	0.962
3:129061992:A:C	N85H	0.961

dbSNP variants (sampled 300 via entrez): RS1000145108 (3:129057851 G>T), RS1000337195 (3:129062618 C>T), RS1000447666 (3:129056872 G>A,T), RS1000619770 (3:129057248 G>A), RS1000948698 (3:129057417 C>T), RS1001031418 (3:129062496 T>C,G), RS1001048537 (3:129056836 G>C,T), RS1001306854 (3:129058292 G>A), RS1001618023 (3:129057920 G>A,C), RS1001908827 (3:129053183 A>G), RS1001952058 (3:129059280 A>C), RS1002004061 (3:129058896 T>A,C,G), RS1002531256 (3:129052859 T>A,C), RS1002982269 (3:129059729 A>G), RS1003057222 (3:129059425 G>A)

Disease associations

OMIM: gene MIM:173515 | disease phenotypes: MIM:231200

GenCC curated gene-disease

Disease	Classification	Inheritance
Bernard-Soulier syndrome	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Bernard-Soulier syndrome	Definitive	AR

Mondo (2): thrombocytopenia (MONDO:0002049), Bernard-Soulier syndrome (MONDO:0009276)

Orphanet (1): Bernard-Soulier syndrome (Orphanet:274)

HPO phenotypes

27 total (27 of 27 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000132	Menorrhagia
HP:0000225	Gingival bleeding
HP:0000421	Epistaxis
HP:0000967	Petechiae
HP:0000978	Bruising susceptibility
HP:0000979	Purpura
HP:0001250	Seizure
HP:0001873	Thrombocytopenia
HP:0001892	Abnormal bleeding
HP:0001902	Giant platelets
HP:0002076	Migraine
HP:0002099	Asthma
HP:0002239	Gastrointestinal hemorrhage
HP:0002248	Hematemesis
HP:0003010	Prolonged bleeding time
HP:0003577	Congenital onset
HP:0004406	Spontaneous, recurrent epistaxis
HP:0004846	Prolonged bleeding after surgery
HP:0006298	Prolonged bleeding after dental extraction
HP:0007420	Spontaneous hematomas
HP:0008738	Partially duplicated kidney
HP:0011871	Impaired ristocetin-induced platelet aggregation
HP:0011879	Decreased platelet glycoprotein Ib-IX-V
HP:0012143	Abnormal megakaryocyte morphology
HP:0012587	Macroscopic hematuria
HP:0040185	Macrothrombocytopenia

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST90002395_387	Mean platelet volume	3.000000e-23
GCST90002400_399	Plateletcrit	8.000000e-14
GCST90002401_129	Platelet distribution width	2.000000e-26
GCST90002402_327	Platelet count	1.000000e-35

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0004309	platelet count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001606	Bernard-Soulier Syndrome	C15.378.100.100.080; C15.378.140.120; C15.378.463.080; C16.320.099.080
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
nickel sulfate	increases expression	1
phosphatidylinositol 3,4,5-triphosphate	affects binding, increases abundance	1
tebuconazole	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Benzene	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	increases expression	1
Endosulfan	decreases expression	1
Triclosan	increases methylation	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

3 cell lines: 3 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_DQ80	BSS1-PBMC-iPS4F4	Induced pluripotent stem cell	Female
CVCL_QX24	BSS3-PBMC-iPS4F8	Induced pluripotent stem cell	Female
CVCL_QX25	BSS2-PBMC-iPS4F24	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

240 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients
NCT06562738	PHASE4	RECRUITING	Clinical Study on Efficacy and Safety of Hetrombopag in the Preoperative Patients of Thrombocytopenia
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00073580	PHASE3	COMPLETED	Angiomax in Patients With HIT/HITTS Type II Undergoing Off-Pump Coronary Artery Bypass Grafting (CABG) (CHOOSE)
NCT00102323	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
NCT00102336	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy
NCT00116688	PHASE3	COMPLETED	Open Label Extension Study of Romiplostim (AMG 531) in Thrombocytopenic Patients With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
NCT00128713	PHASE3	COMPLETED	Optimal Platelet Dose Strategy for Management of Thrombocytopenia
NCT00151866	PHASE3	COMPLETED	Efficacy of Transfusions With Platelets Stored in Platelet Additive Solution II Versus Plasma
NCT00261924	PHASE3	COMPLETED	Efficacy and Safety Study of Platelets Treated for Pathogen Inactivation and Stored for Up to Seven Days
NCT00415532	PHASE3	COMPLETED	Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura
NCT00420914	PHASE3	TERMINATED	Strategies for Transfusion of Platelets (SToP)
NCT00501345	PHASE3	TERMINATED	Aspirin in Patients With Myocardial Infarction and Thrombocytopenia
NCT00508820	PHASE3	COMPLETED	An Open Label Study of Romiplostim in Adult Thrombocytopenic Subjects With ITP
NCT00678587	PHASE3	TERMINATED	Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures
NCT01438840	PHASE3	COMPLETED	Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)
NCT01444417	PHASE3	COMPLETED	Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients
NCT01805648	PHASE3	UNKNOWN	Efficacy and Safety Study of Maintenance Treatment With rhTPO in Thrombocytopenic Subjects With ITP
NCT02244658	PHASE3	UNKNOWN	Recombinant Human Thrombopoietin (rhTPO) in Management of Chemotherapy-induced Thrombocytopenia in Acute Myelocytic Leukemia
NCT02389621	PHASE3	COMPLETED	Safety and Efficacy Study of Lusutrombopag for Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Elective Invasive Procedures
NCT02444728	PHASE3	TERMINATED	Cyclophosphamide and Hydroxychloroquine for Thrombocytopenia in SLE
NCT02487563	PHASE3	COMPLETED	Prospective Study of Patients With Thrombocytopenia Following HSCT
NCT02578901	PHASE3	COMPLETED	American Trial Using Tranexamic Acid in Thrombocytopenia
NCT03326843	PHASE3	TERMINATED	Avatrombopag for the Treatment of Thrombocytopenia in Adults Scheduled for a Surgical Procedure
NCT03515096	PHASE3	COMPLETED	Eltrombopag vs. rhTPO to Increase Platelet Level After HSCT
NCT05563064	PHASE3	UNKNOWN	Effect of Herbal Formulation on Thrombocytes Count
NCT07442513	PHASE3	RECRUITING	Comparison of Etamsylate Versus Placebo to Prevent Bleeding in HSCT