GP1BB

Summary

GP1BB (glycoprotein Ib platelet subunit beta, HGNC:4440) is a protein-coding gene on chromosome 22q11.21, encoding Platelet glycoprotein Ib beta chain (P13224). Gp-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to von Willebrand factor, which is already bound to the subendothelium.

Platelet glycoprotein Ib (GPIb) is a heterodimeric transmembrane protein consisting of a disulfide-linked 140 kD alpha chain and 22 kD beta chain. It is part of the GPIb-V-IX system that constitutes the receptor for von Willebrand factor (VWF), and mediates platelet adhesion in the arterial circulation. GPIb alpha chain provides the VWF binding site, and GPIb beta contributes to surface expression of the receptor and participates in transmembrane signaling through phosphorylation of its intracellular domain. Mutations in the GPIb beta subunit have been associated with Bernard-Soulier syndrome, velocardiofacial syndrome and giant platelet disorder. The 206 amino acid precursor of GPIb beta is synthesized from a 1.0 kb mRNA expressed in plateletes and megakaryocytes. A 411 amino acid protein arising from a longer, unspliced transcript in endothelial cells has been described; however, the authenticity of this product has been questioned. Yet another less abundant GPIb beta mRNA species of 3.5 kb, expressed in nonhematopoietic tissues such as endothelium, brain and heart, was shown to result from inefficient usage of a non-consensus polyA signal in the neighboring upstream gene (SEPT5, septin 5). In the absence of polyadenylation from its own imperfect site, the SEPT5 gene produces read-through transcripts that use the consensus polyA signal of this gene.

Source: NCBI Gene 2812 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Bernard-Soulier syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 151 total — 12 pathogenic, 33 likely-pathogenic
• Phenotypes (HPO): 167
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000407

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4440
Approved symbol	GP1BB
Name	glycoprotein Ib platelet subunit beta
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Aliases	CD42c, GPIbbeta
Ensembl gene	ENSG00000203618
Ensembl biotype	protein_coding
OMIM	138720
Entrez	2812

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000366425, ENST00000909123

RefSeq mRNA: 1 — MANE Select: NM_000407 NM_000407

CCDS: CCDS42980

Canonical transcript exons

ENST00000366425 — 2 exons

Exon	Start	End
ENSE00001543380	19723854	19724771
ENSE00001543381	19723539	19723579

Expression profiles

Bgee: expression breadth ubiquitous, 121 present calls, max score 98.79.

FANTOM5 (CAGE): breadth broad, TPM avg 18.4519 / max 814.8784, expressed in 359 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191060	18.4519	359

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.79	gold quality
leukocyte	CL:0000738	98.20	gold quality
granulocyte	CL:0000094	93.15	gold quality
blood	UBERON:0000178	92.32	gold quality
primary visual cortex	UBERON:0002436	87.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.24	gold quality
lower esophagus mucosa	UBERON:0035834	79.55	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.45	gold quality
bone marrow cell	CL:0002092	76.58	gold quality
spleen	UBERON:0002106	67.98	gold quality
superior frontal gyrus	UBERON:0002661	66.10	gold quality
sural nerve	UBERON:0015488	65.61	silver quality
ventricular zone	UBERON:0003053	64.78	gold quality
right lung	UBERON:0002167	62.57	gold quality
bone marrow	UBERON:0002371	61.06	gold quality
calcaneal tendon	UBERON:0003701	60.04	gold quality
ganglionic eminence	UBERON:0004023	55.41	gold quality
right lobe of thyroid gland	UBERON:0001119	54.67	gold quality
hindlimb stylopod muscle	UBERON:0004252	53.67	gold quality
right lobe of liver	UBERON:0001114	51.23	gold quality
endometrium	UBERON:0001295	50.42	gold quality
left lobe of thyroid gland	UBERON:0001120	49.54	gold quality
placenta	UBERON:0001987	48.80	gold quality
liver	UBERON:0002107	48.11	gold quality
muscle tissue	UBERON:0002385	47.56	gold quality
adult mammalian kidney	UBERON:0000082	47.19	gold quality
thyroid gland	UBERON:0002046	47.05	gold quality
smooth muscle tissue	UBERON:0001135	46.53	gold quality
putamen	UBERON:0001874	46.44	gold quality
cortex of kidney	UBERON:0001225	46.36	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-GEOD-149689	yes	5034.89
E-HCAD-4	yes	2821.50
E-MTAB-9221	yes	2622.99
E-MTAB-9388	yes	2522.13
E-CURD-122	yes	1401.31
E-HCAD-1	yes	1333.72
E-GEOD-139324	yes	852.85
E-HCAD-9	yes	696.61
E-MTAB-8207	yes	647.76
E-MTAB-9467	yes	596.06
E-CURD-55	yes	488.75
E-MTAB-10042	yes	256.69
E-HCAD-6	yes	25.34
E-MTAB-9067	yes	11.83
E-GEOD-99795	no	2.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA1

miRNA regulators (miRDB)

12 targeting GP1BB, 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-6721-5P	99.93	68.92	2981
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-6811-5P	97.98	64.96	848
HSA-MIR-383-5P	96.86	67.55	820
HSA-MIR-4433A-5P	96.79	65.01	599
HSA-MIR-2861	95.24	65.47	1056

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Lateral clustering of platelet GP Ib-IX complexes leads to up-regulation of the adhesive function of integrin alpha IIbbeta 3 (PMID:11812775)
• Role of GPIbbeta in modulating vWF mediated platelet adhesion. (PMID:11816713)
• A GP1BB missense mutation suppresses GPIb/IX complex expression and is found to cause Bernard-Soulier Syndrome in the homozygous form and giant platelets in the heterozygous form. (PMID:11816714)
• 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)
• structure-activity relationship of mutations found in Bernard-Soulier syndrome (PMID:12463594)
• The GPIb beta intracellular domain has a role in controlling the adhesive properties of the GPIb/V/IX complex through phosphorylation of GPIb beta Ser166 and point to the existence of cross-talk between the GPIb beta and GPIb alpha intracellular domains. (PMID:12522011)
• novel hemizygous variant of Bernard-Soulier Syndrome in which Pro29 in one GPIbbeta allele is substituted by a Leu (PMID:12529755)
• To determine the sequence in the beta3 cytoplasmic domain that is critical to integrin signaling, cell lines were established that coexpress the platelet receptor for GP1BB. (PMID:12860973)
• identified novel GPIbbeta mutation is responsible for the Bernard-Soulier syndrome phenotype and provide an explanation for the molecular mechanism underlying the reduced platelet content of GPIb-IX complex in the heterozygous individuals studied (PMID:12958615)
• The SEPT5 gene resides approximately 250 nucleotides 5’ to the GP Ibbeta gene and has been associated with modulating exocytosis from neurons and platelets as part of a presynaptic protein complex (PMID:15213102)
• REVIEW OF GP1BB AND GP1BA BINDING SITES FOR LIGANDS, INTERACTIONS WITH VWF AND THROMBIN, ROLE IN PLATELET ACTIVATION (PMID:17597992)
• 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)
• Velocardiofacial syndrome patients have in-vitro defects in platelet function that may increase their risk of bleeding during surgery. (PMID:18064328)
• the N1421K substitution in the VWF affects the GPIb binding site or a recognition element by a conformational change of the A1 domain. (PMID:18637125)
• 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)
• proplatelet formation in human megakaryocytes undergoes a complex spatio-temporal regulation orchestrated by adhesive proteins, GPIb-IX-V and myosin IIA (PMID:18752571)
• novel Ser 23 Stop mutation in GPIbbeta is responsible of BSS in the studied family and hampers the complex to form on the platelets surface. (PMID:18825380)
• A novel variant of Bernard Soulier syndrome is described in which Ser23 of GPIbbeta is substituted by a Stop codon causing a premature termination of translation. (PMID:19484238)
• 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)
• Identify TRAF4 as a novel binding partner for GPIb-IX-V and GPVI in human platelets. (PMID:20946164)
• -induced activation of GpIb-V-IX triggers platelet procoagulant activity and anchorage of a star-like fibrin network. (PMID:21037087)
• 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)
• A 14-month-old boy with Bernard-Soulier syndrome was found to be homozygous for a nonsense mutation (c.423C > A) in the glycoprotein Ib-beta. (PMID:22343686)
• a suspicion of 22q11.2 deletion is warranted in pediatric BSS patients with a mutation in the GPIbbeta gene, even without remarkable symptoms. (PMID:23566026)
• 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)
• Low levels of CD9 coincidental with a novel nonsense mutation in glycoprotein Ibbeta in a patient with Bernard-Soulier syndrome. (PMID:26275786)
• miR-10a and miR10b regulate the expression of human platelet GP1BA and GP1bb for normal megakaryopoiesis. (PMID:27834869)
• Rare variants in GP1BB are responsible for autosomal dominant macrothrombocytopenia. (PMID:28064200)
• New heterozygous variant in GP1BB gene is responsible for an inherited form of macrothrombocytopenia. (PMID:29527674)
• loss of CD34 and expression of CD42b define cells capable of factor V endocytosis and trafficking to proplatelet extensions during differentiation of megakaryocytes ex vivo from progenitor cells isolated from umbilical cord blood (PMID:29761851)
• GPIBB hemizygosity does not result in either macrothrombocytopenia or bleeding in patients with 22q11 deletion syndrome. (PMID:30549403)
• High prevalence of the natural Asn89Asp mutation in the GP1BB gene associated with Bernard-Soulier syndrome in French patients from the genetic isolate of Reunion Island. (PMID:31997307)
• A Sardinian founder mutation in glycoprotein Ib platelet subunit beta (GP1BB) that impacts thrombocytopenia. (PMID:33216977)
• A novel frameshift GP1BB mutation causes autosomal dominant macrothrombocytopenia with decreased vWF receptor expression but normal platelet aggregation. (PMID:33813986)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	gp1bb	ENSDARG00000074441
mus_musculus	Gp1bb	ENSMUSG00000050761

Paralogs (1): GP9 (ENSG00000169704)

Protein

Protein identifiers

Platelet glycoprotein Ib beta chain — P13224 (reviewed: P13224)

Alternative names: Antigen CD42b-beta

All UniProt accessions (1): P13224

UniProt curated annotations — full annotation on UniProt →

Function. Gp-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to von Willebrand factor, which is already bound to the subendothelium.

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. Interacts with TRAF4.

Subcellular location. Membrane.

Tissue specificity. Expressed in heart and brain.

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.

Isoforms (2)

UniProt ID	Names	Canonical?
P13224-1	1	yes
P13224-2	2

RefSeq proteins (1): NP_000398* (*=MANE)

Domains & families (InterPro)

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

UniProt features (34 total): helix 7, disulfide bond 5, strand 5, turn 3, sequence variant 2, topological domain 2, domain 2, modified residue 2, signal peptide 1, chain 1, glycosylation site 1, splice variant 1, transmembrane region 1, repeat 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3RFE	X-RAY DIFFRACTION	1.25
3REZ	X-RAY DIFFRACTION	2.35
8WFS	ELECTRON MICROSCOPY	3.36

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13224-F1	88.43	0.73

Functional residue map

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

Post-translational modifications (2): 191, 193

Disulfide bonds (5): 26–32, 30–39, 93–118, 95–141, 147

Glycosylation sites (1): 66

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: 494 (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, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, BROWNE_HCMV_INFECTION_16HR_UP, ADDYA_ERYTHROID_DIFFERENTIATION_BY_HEMIN, BROWNE_HCMV_INFECTION_12HR_UP, GOBP_MONOATOMIC_CATION_TRANSPORT

GO Biological Process (9): cell adhesion (GO:0007155), cell surface receptor signaling pathway (GO:0007166), blood coagulation, intrinsic pathway (GO:0007597), positive regulation of platelet activation (GO:0010572), platelet activation (GO:0030168), megakaryocyte development (GO:0035855), release of sequestered calcium ion into cytosol (GO:0051209), blood coagulation (GO:0007596), hemostasis (GO:0007599)

GO Molecular Function (3): transmembrane signaling receptor activity (GO:0004888), identical protein binding (GO:0042802), 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
signal transduction	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
cell activation	1
blood coagulation	1
megakaryocyte differentiation	1
myeloid cell development	1
intercellular transport	1
calcium ion transmembrane import into cytosol	1
hemostasis	1
wound healing	1
coagulation	1
regulation of body fluid levels	1
signaling receptor activity	1
protein binding	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

1138 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GP1BB	GP1BA	P07359	999
GP1BB	GP9	P14770	986
GP1BB	VWF	P04275	983
GP1BB	GP5	P40197	969
GP1BB	SEPTIN5	Q99719	898
GP1BB	GNB1L	Q9BYB4	870
GP1BB	YWHAZ	P29213	849
GP1BB	TRAF4	Q9BUZ4	762
GP1BB	ITGA2B	P08514	749
GP1BB	CALM1	P02593	708
GP1BB	CALML6	Q8TD86	708
GP1BB	CALML3	P27482	708
GP1BB	CALML5	Q9NZT1	708
GP1BB	CALML4	Q96GE6	708
GP1BB	TBX1	O43435	702

IntAct

54 interactions, top by confidence:

A	B	Type	Score
GP9	GP1BA	psi-mi:“MI:0914”(association)	0.790
GP1BA	GP1BB	psi-mi:“MI:0407”(direct interaction)	0.700
GP1BA	GP1BB	psi-mi:“MI:0915”(physical association)	0.700
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
GP1BB	GP1BB	psi-mi:“MI:0915”(physical association)	0.530
GP1BB	GP1BB	psi-mi:“MI:0407”(direct interaction)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
SLC39A5	TMEM223	psi-mi:“MI:0914”(association)	0.530
TSPAN17	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
GABRE	FZD6	psi-mi:“MI:0914”(association)	0.530
TSPAN5	SC5D	psi-mi:“MI:0914”(association)	0.530
SIDT2	AP3D1	psi-mi:“MI:0914”(association)	0.530
CCDC47	ESYT2	psi-mi:“MI:0914”(association)	0.350
TSPAN15	TMEM223	psi-mi:“MI:0914”(association)	0.350
AMIGO1	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
LDLRAD1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC2D	TMEM120B	psi-mi:“MI:0914”(association)	0.350
LRRC55	TMEM120B	psi-mi:“MI:0914”(association)	0.350
ZDHHC12	NBAS	psi-mi:“MI:0914”(association)	0.350
ZACN	FAM234B	psi-mi:“MI:0914”(association)	0.350
CLRN2	FAM234B	psi-mi:“MI:0914”(association)	0.350
CHRNB2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SIDT2	KLRG2	psi-mi:“MI:0914”(association)	0.350

BioGRID (88): GP1BB (Affinity Capture-MS), GP1BB (Affinity Capture-MS), GP1BB (Affinity Capture-MS), GP1BB (Affinity Capture-MS), GP1BB (Affinity Capture-MS), GP1BB (Affinity Capture-MS), GP1BB (Affinity Capture-MS), GP1BB (Affinity Capture-MS), GP1BB (Affinity Capture-MS), GP1BB (Affinity Capture-MS), GP1BB (Affinity Capture-MS), GP1BB (Affinity Capture-MS), GP1BB (Affinity Capture-MS), GP1BB (Affinity Capture-MS), GP1BB (Affinity Capture-MS)

ESM2 similar proteins: A0A8I5KY20, A2A9Q0, A9JSM3, C9JI98, D4A2Q0, D4ABX8, E7ERA6, F1SAM7, F2Z333, O94819, P0C7J6, P0CG25, P13224, P56400, Q04785, Q0GA42, Q17QZ8, Q1RMK9, Q2MJR0, Q2WF71, Q504Y2, Q50LG9, Q5RJI4, Q6IEE6, Q6IEE7, Q6IQX7, Q6P6N5, Q6PJG9, Q6UKI2, Q6UX72, Q6ZMC9, Q6ZT52, Q6ZVX7, Q7Z6J2, Q80XU8, Q86UD0, Q86VR8, Q8BQB4, Q8IZ52, Q8QZV0

Diamond homologs: A8WGA3, B1H134, B1H234, D3ZTV3, D4ABX8, F1NUK7, G5EFX6, O42235, O43155, O55226, O60938, O75093, O88279, O88280, O94769, O94991, P04629, P13224, P14770, P24014, P50608, P50609, P56400, P59383, P83503, Q04785, Q06828, Q3UHC2, Q5R6T0, Q5RAC4, Q5RI43, Q6RKD8, Q6WRH9, Q70AK3, Q7Z2Q7, Q80TR4, Q80XU8, Q810B7, Q810C1, Q8BGT1

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
GP1BB	“form complex”	“GPIb-IX-V complex”	binding
PRKACA	“down-regulates activity”	GP1BB	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 66 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neurotransmitter receptors and postsynaptic signal transmission	5	13.2×	7e-04
Transmission across Chemical Synapses	6	12.0×	3e-04
Neuronal System	6	7.0×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
monoatomic ion transmembrane transport	7	25.1×	5e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	33
Uncertain significance	75
Likely benign	19
Benign	6

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1338488	NM_000407.5(GP1BB):c.1A>G (p.Met1Val)	Pathogenic
1338624	NM_000407.5(GP1BB):c.448dup (p.Ala150fs)	Pathogenic
16039	NM_000407.5(GP1BB):c.397G>C (p.Ala133Pro)	Pathogenic
16041	NR_037611.1(SEPT5-GP1BB):n.3581C>G	Pathogenic
1691232	NM_000407.5(GP1BB):c.443G>A (p.Trp148Ter)	Pathogenic
1691255	NM_000407.5(GP1BB):c.317_320dup (p.Glu109fs)	Pathogenic
1703862	NM_000407.5(GP1BB):c.22dup (p.Ala8fs)	Pathogenic
2572122	NM_000407.5(GP1BB):c.124_145del (p.Arg42fs)	Pathogenic
3380918	NM_000407.5(GP1BB):c.315del (p.Gly106fs)	Pathogenic
395268	GRCh37/hg19 22q11.21(chr22:18894339-20255110)x1	Pathogenic
4687727	NC_000022.10:g.(?19711061)(19712295_?)del	Pathogenic
627237	NM_000407.5(GP1BB):c.143C>A (p.Ser48Ter)	Pathogenic
158610	NM_000407.5(GP1BB):c.340C>T (p.Arg114Cys)	Likely pathogenic
16038	NM_000407.5(GP1BB):c.338A>G (p.Tyr113Cys)	Likely pathogenic
16040	NM_000407.5(GP1BB):c.137G>A (p.Trp46Ter)	Likely pathogenic
1678696	NM_000407.5(GP1BB):c.473T>G (p.Leu158Arg)	Likely pathogenic
1679210	NM_000407.5(GP1BB):c.406G>T (p.Glu136Ter)	Likely pathogenic
1691253	NM_000407.5(GP1BB):c.1A>T (p.Met1Leu)	Likely pathogenic
1691254	NM_000407.5(GP1BB):c.268C>T (p.Pro90Ser)	Likely pathogenic
1695035	NM_000407.5(GP1BB):c.179T>C (p.Leu60Pro)	Likely pathogenic
1703859	NM_000407.5(GP1BB):c.491dup (p.His164fs)	Likely pathogenic
1703860	NM_000407.5(GP1BB):c.462_511del (p.Gln154fs)	Likely pathogenic
1705376	NM_000407.5(GP1BB):c.2T>C (p.Met1Thr)	Likely pathogenic
2572096	NM_000407.5(GP1BB):c.536_545del (p.Arg179fs)	Likely pathogenic
2572149	NM_000407.5(GP1BB):c.272G>A (p.Trp91Ter)	Likely pathogenic
2664802	NM_000407.5(GP1BB):c.240_246dup (p.Thr83fs)	Likely pathogenic
3065872	NM_000407.5(GP1BB):c.53_65del (p.Pro18fs)	Likely pathogenic
3775055	NM_000407.5(GP1BB):c.439T>A (p.Cys147Ser)	Likely pathogenic
3775056	NM_000407.5(GP1BB):c.269C>G (p.Pro90Arg)	Likely pathogenic
4849245	NM_000407.5(GP1BB):c.89G>A (p.Cys30Tyr)	Likely pathogenic

SpliceAI

146 predictions. Top by Δscore:

Variant	Effect	Δscore
22:19723542:GA:G	donor_gain	0.9500
22:19723544:G:GG	donor_gain	0.9200
22:19723580:G:GA	donor_loss	0.9000
22:19723581:T:TG	donor_loss	0.9000
22:19723584:G:C	donor_loss	0.9000
22:19723583:AGTC:A	donor_loss	0.8900
22:19723580:G:GG	donor_gain	0.8800
22:19723543:A:AG	donor_gain	0.8300
22:19723714:G:GA	donor_gain	0.8300
22:19723848:TTGCA:T	acceptor_loss	0.8300
22:19723849:TGCA:T	acceptor_loss	0.8300
22:19723850:GCAG:G	acceptor_loss	0.8300
22:19723851:CAGG:C	acceptor_loss	0.8300
22:19723852:A:C	acceptor_loss	0.8300
22:19723853:G:GT	acceptor_loss	0.8300
22:19723852:A:AG	acceptor_gain	0.8200
22:19723853:G:GG	acceptor_gain	0.8200
22:19723853:GGGCC:G	acceptor_gain	0.8000
22:19723647:T:TA	donor_gain	0.7600
22:19723690:G:T	donor_gain	0.7600
22:19723852:AG:A	acceptor_gain	0.7600
22:19723853:GG:G	acceptor_gain	0.7600
22:19723713:T:TA	donor_gain	0.7500
22:19723846:CCTTG:C	acceptor_loss	0.7500
22:19723847:CTTGC:C	acceptor_loss	0.7500
22:19723664:G:GT	donor_gain	0.7300
22:19723539:GCAGA:G	donor_gain	0.7000
22:19723845:CCCTT:C	acceptor_loss	0.6900
22:19723666:A:T	donor_gain	0.6100
22:19723841:GCTTC:G	acceptor_loss	0.6100

AlphaMissense

1237 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:19724037:A:T	N65I	0.996
22:19724116:G:C	W91C	0.996
22:19724116:G:T	W91C	0.996
22:19724038:C:A	N65K	0.994
22:19724038:C:G	N65K	0.994
22:19724152:G:C	W103C	0.990
22:19724152:G:T	W103C	0.990
22:19724114:T:A	W91R	0.986
22:19724114:T:C	W91R	0.986
22:19723959:G:A	C39Y	0.985
22:19724001:T:G	F53C	0.985
22:19724110:C:A	N89K	0.985
22:19724110:C:G	N89K	0.985
22:19724036:A:T	N65Y	0.979
22:19724108:A:T	N89Y	0.979
22:19724195:T:A	C118S	0.978
22:19724196:G:C	C118S	0.978
22:19723958:T:A	C39S	0.976
22:19723959:G:C	C39S	0.976
22:19724120:T:A	C93S	0.976
22:19724121:G:C	C93S	0.976
22:19724109:A:T	N89I	0.975
22:19723960:C:G	C39W	0.973
22:19724121:G:A	C93Y	0.973
22:19723959:G:T	C39F	0.971
22:19724001:T:C	F53S	0.971
22:19724037:A:C	N65T	0.969
22:19724115:G:C	W91S	0.968
22:19724195:T:C	C118R	0.967
22:19724196:G:A	C118Y	0.967

dbSNP variants (sampled 300 via entrez): RS1000060878 (22:19723059 C>G,T), RS1000070980 (22:19722911 T>A,C), RS1000267092 (22:19723150 C>T), RS1001152173 (22:19724339 T>TTGC), RS1002664845 (22:19724551 C>G,T), RS1004634614 (22:19724976 G>A), RS1004688438 (22:19724699 G>C), RS1006371354 (22:19723357 C>A,T), RS1007110913 (22:19722304 G>A), RS1008399018 (22:19722093 T>A,C), RS1008808696 (22:19721968 C>G,T), RS1010406568 (22:19724392 C>A,T), RS1010810536 (22:19724172 G>A,C,T), RS1011240949 (22:19722402 A>C,T), RS1011314180 (22:19723861 C>G,T)

Disease associations

OMIM: gene MIM:138720 | disease phenotypes: MIM:231200

GenCC curated gene-disease

Disease	Classification	Inheritance
Bernard-Soulier syndrome	Definitive	Autosomal recessive
autosomal dominant macrothrombocytopenia	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Bernard-Soulier syndrome	Definitive	AR

Mondo (3): Bernard-Soulier syndrome (MONDO:0009276), thrombocytopenia (MONDO:0002049), autosomal dominant macrothrombocytopenia (MONDO:0015372)

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

HPO phenotypes

167 total (30 of 167 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000076	Vesicoureteral reflux
HP:0000089	Renal hypoplasia
HP:0000113	Polycystic kidney dysplasia
HP:0000130	Abnormality of the uterus
HP:0000132	Menorrhagia
HP:0000160	Narrow mouth
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000225	Gingival bleeding
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000262	Turricephaly
HP:0000272	Malar flattening
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000385	Small earlobe
HP:0000389	Chronic otitis media
HP:0000396	Overfolded helix
HP:0000405	Conductive hearing impairment
HP:0000414	Bulbous nose

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002057_6	DNA methylation (parent-of-origin)	6.000000e-08
GCST004599_219	Mean platelet volume	2.000000e-21
GCST004603_147	Platelet count	1.000000e-12
GCST004616_173	Platelet distribution width	9.000000e-22
GCST90002395_615	Mean platelet volume	1.000000e-73
GCST90002401_342	Platelet distribution width	4.000000e-41
GCST90002402_640	Platelet count	5.000000e-30

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0022599	DNA methylation
EFO:0004309	platelet count
EFO:0007984	platelet component distribution width

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

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium	increases abundance, increases expression	2
hydroxyhydroquinone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
abrine	decreases expression	1
eprenetapopt	increases expression, affects reaction	1
(+)-JQ1 compound	decreases expression	1
Troglitazone	decreases expression	1
Acetaminophen	decreases expression	1
Allergens	increases expression	1
Arsenic	affects expression, increases abundance	1
Benzene	decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Cacodylic Acid	affects expression, increases abundance	1
Carmustine	decreases expression	1
Cisplatin	increases expression	1
Estradiol	increases expression, affects cotreatment	1
Fluorouracil	affects expression	1
Niclosamide	increases expression	1
Phthalic Acids	increases methylation	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Vanadium	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases abundance, increases expression	1
Okadaic Acid	increases expression	1
Acrylamide	decreases expression	1

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