PF4

Summary

PF4 (platelet factor 4, HGNC:8861) is a protein-coding gene on chromosome 4q13.3, encoding Platelet factor 4 (P02776). Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation.

This gene encodes a member of the CXC chemokine family. This chemokine is released from the alpha granules of activated platelets in the form of a homotetramer which has high affinity for heparin and is involved in platelet aggregation. This protein is chemotactic for numerous other cell type and also functions as an inhibitor of hematopoiesis, angiogenesis and T-cell function. The protein also exhibits antimicrobial activity against Plasmodium falciparum.

Source: NCBI Gene 5196 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 15 total
• Druggable target: yes
• MANE Select transcript: NM_002619

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8861
Approved symbol	PF4
Name	platelet factor 4
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	SCYB4, CXCL4
Ensembl gene	ENSG00000163737
Ensembl biotype	protein_coding
OMIM	173460
Entrez	5196

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 nonsense_mediated_decay

ENST00000296029, ENST00000687529

RefSeq mRNA: 2 — MANE Select: NM_002619 NM_001363352, NM_002619

CCDS: CCDS3562

Canonical transcript exons

ENST00000296029 — 3 exons

Exon	Start	End
ENSE00001077821	73980811	73981291
ENSE00001077823	73981863	73982027
ENSE00002471273	73981417	73981543

Expression profiles

Bgee: expression breadth ubiquitous, 151 present calls, max score 99.71.

FANTOM5 (CAGE): breadth broad, TPM avg 24.9612 / max 5065.1124, expressed in 442 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52540	22.6775	277
52539	1.8969	193
52541	0.2473	106
52537	0.0731	10
52538	0.0664	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.71	gold quality
mononuclear cell	CL:0000842	99.66	gold quality
leukocyte	CL:0000738	99.53	gold quality
trabecular bone tissue	UBERON:0002483	98.43	gold quality
granulocyte	CL:0000094	98.20	gold quality
blood	UBERON:0000178	96.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.13	gold quality
bone marrow	UBERON:0002371	92.92	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.56	silver quality
bone marrow cell	CL:0002092	92.10	gold quality
bone element	UBERON:0001474	91.66	gold quality
periodontal ligament	UBERON:0008266	87.85	gold quality
spleen	UBERON:0002106	84.17	gold quality
decidua	UBERON:0002450	82.25	silver quality
biceps brachii	UBERON:0001507	80.25	silver quality
right lung	UBERON:0002167	80.10	gold quality
pancreatic ductal cell	CL:0002079	78.71	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	76.93	gold quality
tendon of biceps brachii	UBERON:0008188	74.94	gold quality
epithelial cell of pancreas	CL:0000083	74.05	gold quality
placenta	UBERON:0001987	72.91	gold quality
upper lobe of left lung	UBERON:0008952	71.95	gold quality
germinal epithelium of ovary	UBERON:0001304	71.71	silver quality
triceps brachii	UBERON:0001509	71.13	gold quality
gluteal muscle	UBERON:0002000	71.09	gold quality
upper lobe of lung	UBERON:0008948	70.27	gold quality
pigmented layer of retina	UBERON:0001782	67.92	silver quality
lung	UBERON:0002048	66.53	gold quality
diaphragm	UBERON:0001103	65.08	gold quality
olfactory bulb	UBERON:0002264	64.39	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-MTAB-10432	yes	34973.25
E-MTAB-9221	yes	26775.00
E-MTAB-8207	yes	19839.15
E-MTAB-6701	yes	17770.13
E-HCAD-4	yes	12711.06
E-HCAD-10	yes	11913.47
E-CURD-112	yes	11227.98
E-GEOD-135922	yes	7154.20
E-HCAD-1	yes	7052.99
E-GEOD-139324	yes	6210.43
E-MTAB-6308	yes	4084.74
E-HCAD-9	yes	3349.93
E-HCAD-24	yes	2127.97
E-HCAD-32	yes	1751.38
E-MTAB-9467	yes	1352.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELF1, ETS1, FLI1, GATA1, GATA2, GATA3, GLI1, MEIS1, PBX1, PBX2, PKNOX1, RUNX1, TIAL1, USF1, USF2, ZNF699

Literature-anchored findings (GeneRIF, showing 40)

• a second epitope for heparin-induced thrombocytopenia/thrombosis antibodies is defined by epitope mapping (PMID:11830470)
• Signaling transduction induced by PF4 in erythroleukemia cells was compared with that induced by TGFB1, which is also a potent inhibitor of HEL growth. (PMID:12041672)
• PF4 inhibits T cell function by down-modulating cell proliferation and cytokine release and therefore has a potential role as a mediator of long-term effects in the regulation of inflammatory processes in vivo. (PMID:12097379)
• CXCL4 at substimulatory dosages modulates CTAP-III- as well as CXCL7-induced adhesion of neutrophils to vascular endothelium. (PMID:12193731)
• Platelet factor 4 induces human natural killer cells to synthesize and release interleukin-8. (PMID:12223528)
• Platelet factor 4 inhibits FGF2-induced endothelial cell proliferation via the extracellular signal-regulated kinase pathway but not by the phosphatidylinositol 3-kinase pathway. (PMID:12384403)
• PF4 may modulate the hematopoietic milieu both by promoting progenitor adhesion and by binding to or interfering with signaling caused by hematopoietically active chemokines, such as IL-8 (PMID:12586630)
• physiologically relevant concentrations of PF4 stimulate thrombin-dependent activated protein C generation in cultured vascular endothelial cells (PMID:12609838)
• PREP1 regulates PF4 gene expression. (PMID:12732210)
• Gene profiling identified PF4 from peripheral blood cells in coronary artery disease. (PMID:12878486)
• results suggested a model by which PF4 bound to proximal (but distinct) sites to antithrombin (AT) resulting in steric interference of factor Xa binding to both polysaccharide and AT (PMID:14575696)
• PF4 neutrophil adhesion is controlled by src-kinases and PF-4-mediated exocytosis requires activation of p38 MAP kinase and phosphatidylinositol 3-kinase (PMID:14592823)
• correlation between PF4 deposition, lesion severity and symptomatic atherosclerosis; PF4 was commonly found in macrophages of early lesions (PMID:14652645)
• Review: PF-4 isinteracts directly with angiogenesis growth factors and inhibits their interaction with cell surface receptors, perhaps playing a role as an endogenous angiogenesis regulator; role in cancer pathology (PMID:15034805)
• PF4 promoters are transactivated by USF1 and 2 which may play an important role in megakaryocytic gene expression (PMID:15187018)
• PF4 caused a prostaglandin-independent, dose-dependent inhibition of human osteosarcoma cell proliferation under various growth conditions (serum-free, serum-stimulated and thrombin-stimulated). (PMID:1520309)
• PF-4 acts on macrophages in a dual manner. PF-4 may play a crucial role in the induction and maintenance of an unspecific immune response. (PMID:15265941)
• PF-4 strongly inhibited the VEGF(165)- and VEGF(121)-induced mitogen-activated protein (MAP) kinase signalling pathways (PMID:15291808)
• The capacity of PF4 to form ultralarge complexes composed of multiple PF4 tetramers arrayed in a lattice with several molecules of unfractionated heparin may play a fundamental role in autoantibody formation, antibody-dependent platelet activation. (PMID:15304392)
• Interactions with PF4 require structural motifs important in RANTES oligomerization and amplify RANTES-triggered effects on monocyte adhesion. (PMID:15459010)
• Induction of E-selectin RNA in umbilical vein endothelial cells exposed to PF4 is time and dose dependent; PF4 induces E-selectin expression by activation of transcriptional activity (PMID:15591119)
• PF4 had an inhibitory activity on megakaryocytopoiesis in vitro and in vivo in mice. (PMID:15622770)
• Human platelet factor 4 stimulates proliferation of naturally anergic human CD4+CD25+ T regulatory cells while inhibiting proliferation of CD4+CD25- T nonregulatory cells. (PMID:15728475)
• Expression of PF4 is up-regulated at the mRNA and protein level by thrombin and mediated by proteinase-activated receptors (PARs), resulting in a 32- to 128-fold higher mRNA level and leading to an up-to-sixfold increase of the peptide concentration. (PMID:15788441)
• analysis of granule targeting sequence within platelet factor 4 (PMID:15964840)
• PTEN expression negatively regulates CXCR4-meidated chemotaxis of lymphoid mammalian cells via its lipid phosphatase activity (PMID:15994292)
• cell-surface PF4 complexes are antigenic only over a restricted concentration range of PF4. Heparin is not required for HIT antibody binding but shifts the concentration of PF4 needed for optimal surface antigenicity to higher levels (PMID:16304054)
• activated human skin mast cells (MCs) convert CTAP-III into biologically active NAP-2 through proteolytic cleavage by released chymase (PMID:16317101)
• Salmonella could be used in vivo as a PF4 DNA delivery vector in the management of radiation injury (PMID:16881736)
• a candidate tumor suppressor gene, platelet factor 4, was frequently silenced by promoter hypermethylation in MM (15 of 28) and MM cell lines (5 of 5) (PMID:17077331)
• CXCL4 seals blood clots by altering the structure of fibrin (PMID:17090548)
• CXCL4 and CXCL4L1 exhibit a distinct subcellular localization and are secreted in a differentially regulated manner, suggesting distinct roles in inflammatory or homeostatic processes. (PMID:17218382)
• CXCL4 decreased serum levels in advanced MDS, suggesting the possibility of a concerted disturbance of transcription or translation of these chemokines in advanced MDS (PMID:17220270)
• angiostatic non-ELR CXC chemokines may increase to balance angiogenic ELR+ CXC chemokines in which increased levels were shown in patients with inflammatory arthritides and CXCL4 may contribute to designate the chronicity of synovitis in patients with RA (PMID:17265155)
• Several PF4 fragments and modified molecules exhibit antiangiogenesis properties and may become an alternative for further therapeutic angiogenesis. (PMID:17381065)
• a high titer of antibodies to PF4 but no relationship was found between that and heparin induced thrombocytopenia or thrombosis in this Turkish population. (PMID:17636189)
• PF4-stimulated immediate monocyte functions (oxygen radical formation) are regulated by p38 MAPK, Syk, and PI3K, whereas delayed functions (survival and cytokine expression) are controlled by Erk and JNK. (PMID:17675521)
• Patients with isolated coronary artery ectasia (CAE) have raised levels of plasma P-selectin, beta-TG and PF4 compared with control participants with angiographically normal coronary arteries, suggesting increased platelet activation in patients with CAE. (PMID:17700216)
• These findings indicate that the equilibrium between angiostatic and angiogenic factors during inflammation and tumor progression is rather complex and differs depending on the chemokine, cell type, and stimulus. (PMID:17827342)
• platelet-associated PF-4, but not its plasma counterpart, may represent a potential biomarker of early tumor presence (PMID:17914028)

Cross-species orthologs

0 orthologs

Paralogs (12): CXCL2 (ENSG00000081041), PF4V1 (ENSG00000109272), CXCL6 (ENSG00000124875), CXCL9 (ENSG00000138755), CXCL13 (ENSG00000156234), CXCL3 (ENSG00000163734), CXCL5 (ENSG00000163735), PPBP (ENSG00000163736), CXCL1 (ENSG00000163739), CXCL10 (ENSG00000169245), CXCL11 (ENSG00000169248), CXCL8 (ENSG00000169429)

Protein

Protein identifiers

Platelet factor 4 — P02776 (reviewed: P02776)

Alternative names: C-X-C motif chemokine 4, Iroplact, Oncostatin-A

All UniProt accessions (2): A0A8I5QJ57, P02776

UniProt curated annotations — full annotation on UniProt →

Function. Chemokine released during platelet aggregation that plays a role in different biological processes including hematopoiesis, cell proliferation, differentiation, and activation. Acts via different functional receptors including CCR1, CXCR3A or CXCR3B. Upon interaction with CXCR3A receptor, induces activated T-lymphocytes migration mediated via downstream Ras/extracellular signal-regulated kinase (ERK) signaling. Neutralizes the anticoagulant effect of heparin by binding more strongly to heparin than to the chondroitin-4-sulfate chains of the carrier molecule. Plays a role in the inhibition of hematopoiesis and in the maintenance of hematopoietic stem cell (HSC) quiescence. Chemotactic for neutrophils and monocytes via CCR1. Inhibits endothelial cell proliferation. In cooperation with toll-like receptor 8/TLR8, induces chromatin remodeling and activates inflammatory gene expression via the TBK1-IRF5 axis. In addition, induces myofibroblast differentiation and collagen synthesis in different precursor cells, including endothelial cells, by stimulating endothelial-to-mesenchymal transition. Interacts with thrombomodulin/THBD to enhance the activation of protein C and thus potentiates its anticoagulant activity.

Subunit / interactions. Homotetramer. Interacts with TNFAIP6 (via Link domain). Interacts with CCR1. Interacts with CXCR3. Interacts with THBD; this interaction enhances generation of activated protein C.

Subcellular location. Secreted.

Induction. By inflammatory conditions.

Similarity. Belongs to the intercrine alpha (chemokine CxC) family.

RefSeq proteins (2): NP_001350281, NP_002610* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001089	Chemokine_CXC	Family
IPR001811	Chemokine_IL8-like_dom	Domain
IPR018048	Chemokine_CXC_CS	Conserved_site
IPR033899	CXC_Chemokine_domain	Domain
IPR036048	Interleukin_8-like_sf	Homologous_superfamily
IPR039809	Chemokine_b/g/d	Family

Pfam: PF00048

UniProt features (19 total): strand 9, chain 2, helix 2, disulfide bond 2, signal peptide 1, binding site 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
1F9Q	X-RAY DIFFRACTION	2
1F9R	X-RAY DIFFRACTION	2
1F9S	X-RAY DIFFRACTION	2.38
1RHP	X-RAY DIFFRACTION	2.4
4R9W	X-RAY DIFFRACTION	2.5
4RAU	X-RAY DIFFRACTION	3.74
4R9Y	X-RAY DIFFRACTION	4.11
1DN3	SOLUTION NMR
1PFM	SOLUTION NMR
1PFN	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02776-F1	75.78	0.24

Antibody-complex structures (SAbDab): 2 — 4R9Y, 4RAU

Functional residue map

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

Ligand- & substrate-binding residues (1): 92–98

Post-translational modifications (1): 57

Disulfide bonds (2): 41–67, 43–83

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-418594	G alpha (i) signalling events
R-HSA-8936459	RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
R-HSA-9769739	Regulation of clotting cascade
R-HSA-140875

MSigDB gene sets: 283 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_REGULATION_OF_COAGULATION, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_PLATELET_ACTIVATION, MODULE_45

GO Biological Process (25): monocyte chemotaxis (GO:0002548), inflammatory response (GO:0006954), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), positive regulation of gene expression (GO:0010628), positive regulation of macrophage derived foam cell differentiation (GO:0010744), negative regulation of angiogenesis (GO:0016525), cytokine-mediated signaling pathway (GO:0019221), platelet activation (GO:0030168), negative regulation of blood coagulation (GO:0030195), neutrophil chemotaxis (GO:0030593), leukocyte chemotaxis (GO:0030595), positive regulation of tumor necrosis factor production (GO:0032760), regulation of cell population proliferation (GO:0042127), defense response to protozoan (GO:0042832), negative regulation of MHC class II biosynthetic process (GO:0045347), positive regulation of macrophage differentiation (GO:0045651), negative regulation of megakaryocyte differentiation (GO:0045653), positive regulation of transcription by RNA polymerase II (GO:0045944), obsolete killing by host of symbiont cells (GO:0051873), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), cellular response to lipopolysaccharide (GO:0071222), negative regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001240), chemotaxis (GO:0006935), defense response (GO:0006952), immune response (GO:0006955)

GO Molecular Function (7): chemokine activity (GO:0008009), heparin binding (GO:0008201), CXCR chemokine receptor binding (GO:0045236), receptor ligand activity (GO:0048018), CXCR3 chemokine receptor binding (GO:0048248), cytokine activity (GO:0005125), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), extracellular matrix (GO:0031012), platelet alpha granule lumen (GO:0031093)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Hemostasis	1
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
Transcriptional regulation by RUNX1	1
Coagulation pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
blood coagulation	2
cell chemotaxis	2
chemokine receptor binding	2
cellular anatomical structure	2
leukocyte chemotaxis	1
mononuclear cell migration	1
myeloid leukocyte migration	1
defense response	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
macrophage derived foam cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
positive regulation of cell differentiation	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
cell activation	1
regulation of blood coagulation	1
negative regulation of coagulation	1
negative regulation of wound healing	1
negative regulation of hemostasis	1
granulocyte chemotaxis	1
neutrophil migration	1
leukocyte migration	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
cell population proliferation	1
regulation of cellular process	1
response to protozoan	1
defense response to other organism	1
negative regulation of macromolecule biosynthetic process	1
MHC class II biosynthetic process	1
regulation of MHC class II biosynthetic process	1
positive regulation of myeloid leukocyte differentiation	1

Protein interactions and networks

STRING

1850 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PF4	CCL5	P13501	996
PF4	CXCR3	P49682	995
PF4	CXCL12	P48061	960
PF4	CXCL11	O14625	956
PF4	CXCL10	P02778	934
PF4	VWF	P04275	929
PF4	CXCL9	Q07325	922
PF4	SELP	P16109	906
PF4	FCGR2A	P12318	891
PF4	CXCL8	P10145	854
PF4	CCR5	P51681	829
PF4	ITGAM	P11215	815
PF4	CXCR2	P25025	801
PF4	HMGB1	P09429	779
PF4	FN1	P02751	770

IntAct

72 interactions, top by confidence:

A	B	Type	Score
PF4	CCL5	psi-mi:“MI:0407”(direct interaction)	0.560
CCL2	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CCL5	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CCL11	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CCL13	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CCL20	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CCL21	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CCL25	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CCL26	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CCL28	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
XCL1	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL2	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL6	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL8	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL9	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL10	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL11	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL12	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL14	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL17	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
PF4	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
PF4	CCL11	psi-mi:“MI:0407”(direct interaction)	0.560
PF4	CCL13	psi-mi:“MI:0407”(direct interaction)	0.560
PF4	CCL21	psi-mi:“MI:0407”(direct interaction)	0.560
PF4	CCL25	psi-mi:“MI:0407”(direct interaction)	0.560
PF4	CCL26	psi-mi:“MI:0407”(direct interaction)	0.560
PF4	CCL28	psi-mi:“MI:0407”(direct interaction)	0.560

BioGRID (44): PF4 (Reconstituted Complex), THBD (Reconstituted Complex), PROC (Reconstituted Complex), PF4 (Co-crystal Structure), LDLR (Reconstituted Complex), PF4 (Co-crystal Structure), PF4 (Reconstituted Complex), PF4 (Reconstituted Complex), PF4 (Reconstituted Complex), PF4 (Reconstituted Complex), PF4 (Reconstituted Complex), PF4 (Reconstituted Complex), PF4 (Reconstituted Complex), PF4 (Reconstituted Complex), PF4 (Reconstituted Complex)

ESM2 similar proteins: A0A0R4INB9, A9QWP9, B0R191, K7XWG4, O43927, O55038, O62812, P02776, P02778, P06765, P10145, P10146, P10720, P17515, P18340, P19874, P22362, P26894, P36925, P41324, P43030, P46653, P48298, P48973, P49113, P67813, P67814, P78556, P79255, P80325, P82943, P97545, P97884, P97885, Q03366, Q07325, Q09141, Q102R3, Q2KIQ8, Q5KSV9

Diamond homologs: A0A0R4INB9, A9QWP9, B0R191, O46675, O46676, O46677, O46678, O55235, O62812, P02775, P02776, P02778, P06765, P08317, P09340, P09341, P10145, P10720, P10889, P12850, P14095, P17515, P18340, P19874, P19875, P19876, P22952, P26894, P30034, P30348, P30782, P36925, P41324, P42830, P43030, P46653, P47854, P48973, P49113, P50228

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 32 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
Chemokine receptors bind chemokines	18	134.8×	3e-35
Interleukin-10 signaling	6	55.9×	9e-09
Peptide ligand-binding receptors	11	32.6×	2e-13
Class A/1 (Rhodopsin-like receptors)	10	29.7×	8e-12
GPCR ligand binding	10	25.7×	3e-11
G alpha (i) signalling events	13	20.3×	2e-13
Signaling by GPCR	10	16.0×	3e-09
Signaling by Interleukins	5	12.8×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
eosinophil chemotaxis	7	171.0×	3e-13
chemokine-mediated signaling pathway	15	162.0×	5e-29
positive regulation of T cell migration	5	122.1×	1e-08
chemotaxis	18	81.5×	3e-29
antimicrobial humoral immune response mediated by antimicrobial peptide	13	70.2×	7e-20
neutrophil chemotaxis	7	66.7×	3e-10
cell chemotaxis	10	61.7×	2e-14
cell-cell signaling	13	30.2×	5e-15

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

300 predictions. Top by Δscore:

Variant	Effect	Δscore
4:73981292:C:CC	acceptor_gain	1.0000
4:73981410:GACTC:G	donor_loss	1.0000
4:73981411:ACTC:A	donor_loss	1.0000
4:73981413:TCAC:T	donor_loss	1.0000
4:73981414:CACAT:C	donor_loss	1.0000
4:73981415:A:AC	donor_gain	1.0000
4:73981415:ACA:A	donor_loss	1.0000
4:73981415:ACAT:A	donor_gain	1.0000
4:73981416:C:CA	donor_gain	1.0000
4:73981416:CA:C	donor_gain	1.0000
4:73981416:CAT:C	donor_gain	1.0000
4:73981416:CATC:C	donor_gain	1.0000
4:73981416:CATCA:C	donor_gain	1.0000
4:73981539:TTCAG:T	acceptor_gain	1.0000
4:73981541:CAG:C	acceptor_gain	1.0000
4:73981544:C:CC	acceptor_gain	1.0000
4:73981819:C:A	donor_gain	1.0000
4:73981841:ACAG:A	donor_gain	1.0000
4:73981842:CAGC:C	donor_gain	1.0000
4:73981861:A:AC	donor_gain	1.0000
4:73981862:C:CC	donor_gain	1.0000
4:73981862:CCG:C	donor_gain	1.0000
4:73981287:TGGCT:T	acceptor_gain	0.9900
4:73981290:CT:C	acceptor_gain	0.9900
4:73981291:TC:T	acceptor_loss	0.9900
4:73981291:TCTG:T	acceptor_gain	0.9900
4:73981459:T:TA	donor_gain	0.9900
4:73981540:TCAG:T	acceptor_gain	0.9900
4:73981541:CAGC:C	acceptor_gain	0.9900
4:73981542:AG:A	acceptor_gain	0.9900

AlphaMissense

640 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:73981289:G:T	A74D	0.982
4:73981259:A:G	L84S	0.951
4:73981435:C:G	C67S	0.948
4:73981436:A:T	C67S	0.948
4:73981262:C:G	C83S	0.934
4:73981263:A:T	C83S	0.934
4:73981436:A:G	C67R	0.934
4:73981471:A:C	I55S	0.932
4:73981263:A:G	C83R	0.929
4:73981513:C:G	C41S	0.929
4:73981514:A:T	C41S	0.929
4:73981471:A:T	I55N	0.927
4:73981261:G:C	C83W	0.926
4:73981507:C:G	C43S	0.925
4:73981508:A:T	C43S	0.925
4:73981420:A:G	L72P	0.917
4:73981514:A:G	C41R	0.913
4:73981262:C:T	C83Y	0.912
4:73981434:G:C	C67W	0.912
4:73981508:A:G	C43R	0.911
4:73981435:C:T	C67Y	0.908
4:73981471:A:G	I55T	0.907
4:73981290:C:G	A74P	0.898
4:73981507:C:T	C43Y	0.880
4:73981436:A:C	C67G	0.874
4:73981274:C:A	G79V	0.869
4:73981435:C:A	C67F	0.862
4:73981283:A:G	L76P	0.858
4:73981263:A:C	C83G	0.855
4:73981462:A:G	L58P	0.849

dbSNP variants (sampled 300 via entrez): RS1000508914 (4:73980742 A>G,T), RS1001114874 (4:73982063 C>A,G,T), RS1001315339 (4:73981798 G>A), RS1001909885 (4:73983821 G>T), RS1002297744 (4:73982395 C>T), RS10027636 (4:73983205 A>T), RS1003183570 (4:73983901 T>A), RS1003299735 (4:73983590 A>G,T), RS1004007582 (4:73981994 G>A,T), RS1004622840 (4:73981718 C>A,G), RS1006040171 (4:73983023 A>T), RS1006075778 (4:73982626 A>G), RS1007898952 (4:73983348 A>G), RS1009118878 (4:73982187 A>C,G), RS1009382610 (4:73980441 T>C)

Disease associations

OMIM: gene MIM:173460 | 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
GCST001639_7	Metabolite levels	3.000000e-10
GCST001725_78	Inflammatory bowel disease	3.000000e-08
GCST009240_348	Serum metabolite levels (CMS)	2.000000e-14
GCST009242_224	Serum metabolite levels	2.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3286075 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 6 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.52	Kd	3000	nM	CHEMBL3288260

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
nonasodium;(2R,3S,4S,5R,6R)-6-[(2R,3S,4R,5R,6R)-5-acetamido-6-[(2R,3S,4S,5R,6R)-6-[(2R,3S,4R,5R,6R)-6-[(2R,3S,4R,5R,6R)-6-[(2R,3S,4R,5R,6S)-5-acetamido-4-hydroxy-6-pentoxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-2-carboxylato-4,5-dihydroxyoxan-3-yl]oxy-4-hydroxy-5-(sulfonatoamino)-2-(sulfonatooxymethyl)oxan-3-yl]oxy-2-carboxylato-4-hydroxy-5-sulfonatooxyoxan-3-yl]oxy-4-hydroxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-3,4-dihydroxy-5-sulfonatooxyoxane-2-carboxylate	1152102: Binding affinity to human recombinant CXCL4 by surface plasmon resonance assay	kd	3.0000	uM

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Heparin	affects binding, increases secretion	4
Benzene	affects expression, decreases expression	3
Valproic Acid	affects expression, increases expression	3
thrombin receptor-activating peptide SFLLRNPNDKY	decreases reaction, increases secretion	2
Adenosine Diphosphate	increases secretion, decreases reaction	2
triphenyl phosphate	affects expression	1
steviol	increases expression	1
stevioside	increases expression	1
silychristin	decreases reaction, increases secretion	1
silidianin	decreases reaction, increases secretion	1
styrofoam	increases secretion	1
rebaudioside A	increases expression	1
CGP 52608	affects binding, increases reaction	1
cangrelor	decreases reaction, increases secretion	1
entinostat	decreases expression	1
Silybin	decreases reaction, increases secretion	1
Air Pollutants	decreases expression, increases abundance	1
Arbutin	decreases expression	1
Arsenic	affects expression	1
Aspirin	decreases reaction, increases secretion	1
Benzo(a)pyrene	affects methylation	1
Cocaine	increases expression	1
Doxorubicin	decreases expression	1
Fructose	increases expression	1
Glucose	increases expression	1
Lipopolysaccharides	increases expression	1
Methotrexate	decreases expression	1
Nortriptyline	affects expression	1
Silicon Dioxide	decreases expression	1
Verapamil	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3293899	Binding	Binding affinity to human recombinant CXCL4 by surface plasmon resonance assay	Synthesis and biological evaluation of a unique heparin mimetic hexasaccharide for structure-activity relationship studies. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A7GW	UKAi002-A-1	Induced pluripotent stem cell	Female
CVCL_A7GX	UKAi002-B-1	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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