GP5

Summary

GP5 (glycoprotein V platelet, HGNC:4443) is a protein-coding gene on chromosome 3q29, encoding Platelet glycoprotein V (P40197). The GPIb-V-IX complex functions as the vWF receptor and mediates vWF-dependent platelet adhesion to blood vessels.

Human platelet glycoprotein V (GP5) is a part of the Ib-V-IX system of surface glycoproteins that constitute the receptor for von Willebrand factor (VWF; MIM 613160) and mediate the adhesion of platelets to injured vascular surfaces in the arterial circulation, a critical initiating event in hemostasis. The main portion of the receptor is a heterodimer composed of 2 polypeptide chains, an alpha chain (GP1BA; MIM 606672) and a beta chain (GP1BB; MIM 138720), that are linked by disulfide bonds. The complete receptor complex includes noncovalent association of the alpha and beta subunits with platelet glycoprotein IX (GP9; MIM 173515) and GP5. Mutations in GP1BA, GP1BB, and GP9 have been shown to cause Bernard-Soulier syndrome (MIM 231200), a bleeding disorder (review by Lopez et al., 1998 [PubMed 9616133]).

Source: NCBI Gene 2814 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 90 total
• MANE Select transcript: NM_004488

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4443
Approved symbol	GP5
Name	glycoprotein V platelet
Location	3q29
Locus type	gene with protein product
Status	Approved
Aliases	CD42d
Ensembl gene	ENSG00000178732
Ensembl biotype	protein_coding
OMIM	173511
Entrez	2814

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000401815, ENST00000692618

RefSeq mRNA: 1 — MANE Select: NM_004488 NM_004488

CCDS: CCDS3307

Canonical transcript exons

ENST00000692618 — 2 exons

Exon	Start	End
ENSE00003927009	194399238	194399266
ENSE00003928529	194394821	194398284

Expression profiles

Bgee: expression breadth broad, 44 present calls, max score 68.19.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0261 / max 15.2469, expressed in 7 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46201	0.0261	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	68.19	gold quality
mononuclear cell	CL:0000842	68.14	gold quality
leukocyte	CL:0000738	68.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	67.39	gold quality
trabecular bone tissue	UBERON:0002483	61.38	silver quality
hair follicle	UBERON:0002073	61.24	gold quality
epithelial cell of pancreas	CL:0000083	58.98	gold quality
right uterine tube	UBERON:0001302	58.05	gold quality
bronchial epithelial cell	CL:0002328	57.95	gold quality
epithelium of bronchus	UBERON:0002031	57.09	silver quality
oviduct epithelium	UBERON:0004804	57.02	silver quality
bronchus	UBERON:0002185	56.48	silver quality
granulocyte	CL:0000094	56.22	gold quality
bone marrow cell	CL:0002092	55.91	silver quality
lymph node	UBERON:0000029	55.55	gold quality
blood	UBERON:0000178	55.40	gold quality
vermiform appendix	UBERON:0001154	55.12	gold quality
caecum	UBERON:0001153	53.04	gold quality
fallopian tube	UBERON:0003889	52.40	gold quality
pancreatic ductal cell	CL:0002079	52.04	silver quality
tibialis anterior	UBERON:0001385	51.92	silver quality
kidney epithelium	UBERON:0004819	51.76	gold quality
bone marrow	UBERON:0002371	51.28	silver quality
nephron tubule	UBERON:0001231	50.86	gold quality
metanephric glomerulus	UBERON:0004736	50.86	gold quality
jejunal mucosa	UBERON:0000399	50.84	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
deltoid	UBERON:0001476	50.39	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1

miRNA regulators (miRDB)

63 targeting GP5, 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-6856-5P	100.00	65.47	1298
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6134	99.63	65.68	1537

Literature-anchored findings (GeneRIF, showing 9)

• Both the high affinity thrombin receptor (GPIb-IX-V) and GPIIb/IIIa are implicated in expression of thrombin-induced platelet procoagulant activity. (PMID:11686325)
• GPV is cleaved upon agonist-induced platelet activation, with ADAM17 as the major enzyme mediating this process (PMID:15691827)
• GPIbalpha and GPV are shed through an ADAM17-dependent mechanism after aspirin administration (PMID:16179345)
• 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)
• 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)
• 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)
• 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)
• GP5 regulates epithelial-mesenchymal transition in breast cancer via the PI3K/AKT signaling pathway. (PMID:35880886)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gp5	ENSMUSG00000047953
rattus_norvegicus	Gp5	ENSRNOG00000038540

Paralogs (25): SLITRK3 (ENSG00000121871), LRFN3 (ENSG00000126243), LRFN1 (ENSG00000128011), SLIT2 (ENSG00000145147), LRFN2 (ENSG00000156564), LRRC38 (ENSG00000162494), SLITRK5 (ENSG00000165300), LRFN5 (ENSG00000165379), LRTM2 (ENSG00000166159), LINGO1 (ENSG00000169783), LRRN2 (ENSG00000170382), LRRN3 (ENSG00000173114), LRFN4 (ENSG00000173621), LINGO2 (ENSG00000174482), LRRN1 (ENSG00000175928), SLITRK1 (ENSG00000178235), SLITRK4 (ENSG00000179542), LRRC55 (ENSG00000183908), SLIT3 (ENSG00000184347), SLITRK6 (ENSG00000184564), SLITRK2 (ENSG00000185985), LRRC70 (ENSG00000186105), SLIT1 (ENSG00000187122), TLR9 (ENSG00000239732), TPBGL (ENSG00000261594)

Protein

Protein identifiers

Platelet glycoprotein V — P40197 (reviewed: P40197)

Alternative names: Glycoprotein 5

All UniProt accessions (1): P40197

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.

Subcellular location. Membrane.

Tissue specificity. Platelets and megakaryocytes.

Post-translational modifications. The N-terminus is blocked.

RefSeq proteins (1): NP_004479* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000483	Cys-rich_flank_reg_C	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050467	LRFN	Family

Pfam: PF01463, PF13855

UniProt features (32 total): repeat 13, glycosylation site 8, sequence conflict 3, domain 2, topological domain 2, signal peptide 1, chain 1, region of interest 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40197-F1	86.99	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.

Glycosylation sites (8): 51, 181, 243, 267, 298, 312, 385, 499

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: 126 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_PROTEIN_ACTIVATION_CASCADE, YAGI_AML_WITH_INV_16_TRANSLOCATION, 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

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 (4): plasma membrane (GO:0005886), extracellular exosome (GO:0070062), 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
extracellular vesicle	1
glycoprotein complex	1
plasma membrane signaling receptor complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1090 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GP5	GP9	P14770	997
GP5	CD151	P48509	994
GP5	CD36	P16671	991
GP5	GP1BB	P13224	969
GP5	VWF	P04275	959
GP5	TXN	P10599	955
GP5	GTPBP1	O00178	950
GP5	GP6	Q9HCN6	949
GP5	SIGLEC1	Q9BZZ2	947
GP5	GP2	P55259	940
GP5	MYOM2	P54296	853
GP5	CWC15	Q9P013	797
GP5	S100A10	P08206	724
GP5	CD163	Q86VB7	698
GP5	GP1BA	P07359	623

IntAct

6 interactions, top by confidence:

A	B	Type	Score
GP9	GP1BA	psi-mi:“MI:0914”(association)	0.790
GP5	GP9	psi-mi:“MI:0915”(physical association)	0.500
GP5	SLC19A2	psi-mi:“MI:0914”(association)	0.350
RAET1L	ENDOD1	psi-mi:“MI:0914”(association)	0.350
GP5	MGST3	psi-mi:“MI:0914”(association)	0.350

BioGRID (63): GP5 (Affinity Capture-MS), CALM1 (Affinity Capture-Western), GP5 (Affinity Capture-MS), GP1BA (Affinity Capture-Western), CNPY3 (Affinity Capture-MS), C4orf32 (Affinity Capture-MS), RHOBTB3 (Affinity Capture-MS), GP5 (Affinity Capture-MS), COX18 (Affinity Capture-MS), SLC19A2 (Affinity Capture-MS), IGSF3 (Affinity Capture-MS), RTN2 (Affinity Capture-MS), VMA21 (Affinity Capture-MS), RTN4 (Affinity Capture-MS), LPHN3 (Affinity Capture-MS)

ESM2 similar proteins: A1A4H9, A4IFA6, A6NDA9, E7FE13, G3XA59, O08644, O08742, O08770, O14498, O15197, P0C0K6, P0C0K7, P35590, P40197, P59383, Q06805, Q06806, Q14392, Q149C3, Q3ZBI5, Q5JZY3, Q5NVQ6, Q5R6B1, Q5RF01, Q5RKR3, Q6EMK4, Q6GU68, Q6P7C4, Q6PFC5, Q6QMY6, Q6UXK2, Q6UY18, Q80ZD5, Q86UE6, Q86WK7, Q86YC3, Q8BGX3, Q8BYG9, Q8C2S7, Q8CBR6

Diamond homologs: O08742, O08770, P40197

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GP5	“form complex”	“GPIb-IX-V complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

9 predictions. Top by Δscore:

Variant	Effect	Δscore
3:194394878:C:CT	acceptor_gain	0.4900
3:194394878:C:T	acceptor_gain	0.4300
3:194397039:T:TA	donor_gain	0.3200
3:194395655:CA:C	acceptor_gain	0.2400
3:194397459:T:TG	acceptor_gain	0.2400
3:194397460:C:A	acceptor_gain	0.2300
3:194397035:G:T	donor_gain	0.2100
3:194395654:CCA:C	acceptor_gain	0.2000
3:194397318:G:C	donor_gain	0.2000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000005179 (3:194398764 T>A,C), RS1000066981 (3:194397189 A>G), RS1000476106 (3:194398337 T>C), RS1000818840 (3:194399394 G>C), RS1000850160 (3:194399813 G>GTTGTTTT), RS1001706985 (3:194394609 T>A), RS1002178418 (3:194399185 G>A), RS1002209580 (3:194398837 C>T), RS1002510772 (3:194400414 C>T), RS1002541726 (3:194400107 G>A), RS1003343507 (3:194395870 C>T), RS1003716783 (3:194397227 G>A,T), RS1003828018 (3:194395702 A>G), RS1006066457 (3:194396504 G>A,C,T), RS1007060791 (3:194398400 C>A,T)

Disease associations

OMIM: gene MIM:173511 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004616_147	Platelet distribution width	1.000000e-13
GCST90002395_556	Mean platelet volume	5.000000e-14
GCST90002401_140	Platelet distribution width	8.000000e-25
GCST90002402_672	Platelet count	1.000000e-12

EFO canonical traits (2, from GWAS)

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

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
Tobacco Smoke Pollution	decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
ochratoxin A	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
phosphatidylinositol 3,4,5-triphosphate	affects binding, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
theaflavin-3,3’-digallate	affects expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Malathion	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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