CXCL3

Summary

CXCL3 (C-X-C motif chemokine ligand 3, HGNC:4604) is a protein-coding gene on chromosome 4q13.3, encoding C-X-C motif chemokine 3 (P19876). Ligand for CXCR2.

This antimicrobial gene encodes a member of the CXC subfamily of chemokines. The encoded protein is a secreted growth factor that signals through the G-protein coupled receptor, CXC receptor 2. This protein plays a role in inflammation and as a chemoattractant for neutrophils.

Source: NCBI Gene 2921 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 19 total — 1 likely-pathogenic
• GTEx eGene: eQTL in 6 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.38 (unconstrained)
• MANE Select transcript: NM_002090

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4604
Approved symbol	CXCL3
Name	C-X-C motif chemokine ligand 3
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	SCYB3, GROg, MIP-2b, CINC-2b
Ensembl gene	ENSG00000163734
Ensembl biotype	protein_coding
OMIM	139111
Entrez	2921

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding_CDS_not_defined, 1 protein_coding

MANE Select: ENST00000296026

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2

ENST00000296026, ENST00000502974, ENST00000510390, ENST00000511669

RefSeq mRNA: 1 — MANE Select: NM_002090 NM_002090

CCDS: CCDS34007

Canonical transcript exons

ENST00000296026 — 4 exons

Exon	Start	End
ENSE00001210973	74036589	74037277
ENSE00002492744	74038512	74038689
ENSE00003621163	74038290	74038413
ENSE00003694657	74038093	74038176

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 94.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.2036 / max 3236.9159, expressed in 1149 samples.

Highest expression (Bgee): cartilage tissue, male germ line stem cell (sensu Vertebrata) in testis, mucosa of paranasal sinus, pylorus, epithelial cell of pancreas.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CXCL3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

6 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Aorta	eqtl	3.0e-03	-1.07	4:73959100:T:G
Nerve Tibial	eqtl	6.9e-03	-0.15	4:74146669:A:G
Thyroid	eqtl	2.5e-02	-0.83	4:73775211:G:C
Breast Mammary Tissue	eqtl	3.2e-02	-0.16	4:74653526:T:C
Skin Not Sun Exposed Suprapubic	eqtl	3.5e-02	-0.72	4:73627429:G:A
Adipose Subcutaneous	eqtl	4.0e-02	-0.14	4:73951126:G:A

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
52549	44.9901	1005
52553	1.0014	403
52550	0.2121	103

Top tissues by expression

showing 100 of 285 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	94.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.09	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.75	gold quality
pylorus	UBERON:0001166	86.55	gold quality
epithelial cell of pancreas	CL:0000083	85.02	gold quality
vermiform appendix	UBERON:0001154	83.85	gold quality
upper lobe of left lung	UBERON:0008952	83.77	gold quality
rectum	UBERON:0001052	83.33	gold quality
upper lobe of lung	UBERON:0008948	82.93	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	81.81	gold quality
islet of Langerhans	UBERON:0000006	80.55	gold quality
vena cava	UBERON:0004087	79.76	gold quality
lung	UBERON:0002048	79.38	gold quality
gall bladder	UBERON:0002110	78.62	gold quality
lower lobe of lung	UBERON:0008949	78.42	silver quality
right lung	UBERON:0002167	78.08	gold quality
palpebral conjunctiva	UBERON:0001812	76.79	gold quality
body of stomach	UBERON:0001161	76.30	gold quality
granulocyte	CL:0000094	76.29	gold quality
caecum	UBERON:0001153	76.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.82	silver quality
monocyte	CL:0000576	75.72	gold quality
mucosa of stomach	UBERON:0001199	75.62	gold quality
endothelial cell	CL:0000115	75.61	silver quality
mononuclear cell	CL:0000842	75.20	gold quality
pleura	UBERON:0000977	74.98	gold quality
visceral pleura	UBERON:0002401	74.89	gold quality
parietal pleura	UBERON:0002400	74.78	gold quality
leukocyte	CL:0000738	74.59	gold quality
omental fat pad	UBERON:0010414	74.37	gold quality
stomach	UBERON:0000945	74.33	gold quality
peritoneum	UBERON:0002358	74.33	gold quality
cardia of stomach	UBERON:0001162	74.25	gold quality
pancreatic ductal cell	CL:0002079	74.20	silver quality
mucosa of sigmoid colon	UBERON:0004993	74.11	gold quality
right atrium auricular region	UBERON:0006631	73.69	gold quality
mucosa of urinary bladder	UBERON:0001259	73.45	gold quality
fundus of stomach	UBERON:0001160	73.19	gold quality
nasal cavity mucosa	UBERON:0001826	73.02	gold quality
adipose tissue of abdominal region	UBERON:0007808	72.78	gold quality
cardiac atrium	UBERON:0002081	72.41	gold quality
minor salivary gland	UBERON:0001830	72.14	gold quality
smooth muscle tissue	UBERON:0001135	71.66	gold quality
colonic mucosa	UBERON:0000317	71.29	gold quality
sperm	CL:0000019	71.16	silver quality
saliva-secreting gland	UBERON:0001044	70.81	gold quality
transverse colon	UBERON:0001157	69.84	gold quality
mouth mucosa	UBERON:0003729	69.82	gold quality
amniotic fluid	UBERON:0000173	69.75	gold quality
stromal cell of endometrium	CL:0002255	69.74	gold quality
pancreas	UBERON:0001264	69.54	gold quality
male germ cell	CL:0000015	69.50	silver quality
nasal cavity epithelium	UBERON:0005384	68.61	silver quality
large intestine	UBERON:0000059	66.74	gold quality
spleen	UBERON:0002106	66.70	gold quality
germinal epithelium of ovary	UBERON:0001304	66.55	gold quality
epithelium of bronchus	UBERON:0002031	66.16	silver quality
colon	UBERON:0001155	66.14	gold quality
bronchus	UBERON:0002185	66.13	silver quality
bronchial epithelial cell	CL:0002328	66.08	gold quality
epithelium of nasopharynx	UBERON:0001951	65.52	silver quality
intestine	UBERON:0000160	65.33	gold quality
left uterine tube	UBERON:0001303	65.13	gold quality
right lobe of liver	UBERON:0001114	64.66	gold quality
colonic epithelium	UBERON:0000397	64.51	gold quality
ascending aorta	UBERON:0001496	64.48	gold quality
heart	UBERON:0000948	64.12	gold quality
small intestine Peyer’s patch	UBERON:0003454	64.09	gold quality
secondary oocyte	CL:0000655	63.99	gold quality
thoracic aorta	UBERON:0001515	63.92	gold quality
mucosa of transverse colon	UBERON:0004991	63.63	gold quality
adipose tissue	UBERON:0001013	63.21	gold quality
body of pancreas	UBERON:0001150	63.21	gold quality
gingival epithelium	UBERON:0001949	63.04	gold quality
layer of synovial tissue	UBERON:0007616	63.03	gold quality
bone marrow cell	CL:0002092	63.02	silver quality
sigmoid colon	UBERON:0001159	62.87	gold quality
connective tissue	UBERON:0002384	62.65	gold quality
heart left ventricle	UBERON:0002084	62.59	gold quality
esophagus squamous epithelium	UBERON:0006920	62.29	silver quality
small intestine	UBERON:0002108	62.24	gold quality
hindlimb stylopod muscle	UBERON:0004252	62.20	gold quality
cardiac ventricle	UBERON:0002082	62.03	gold quality
bone marrow	UBERON:0002371	61.65	gold quality
left coronary artery	UBERON:0001626	61.26	gold quality
lymph node	UBERON:0000029	61.18	gold quality
gingiva	UBERON:0001828	61.16	gold quality
epithelium of esophagus	UBERON:0001976	61.14	silver quality
trachea	UBERON:0003126	61.14	silver quality
aorta	UBERON:0000947	61.12	gold quality
apex of heart	UBERON:0002098	61.12	gold quality
squamous epithelium	UBERON:0006914	60.91	gold quality
buccal mucosa cell	CL:0002336	60.88	gold quality
subcutaneous adipose tissue	UBERON:0002190	60.73	gold quality
liver	UBERON:0002107	60.62	gold quality
coronary artery	UBERON:0001621	60.39	gold quality
muscle layer of sigmoid colon	UBERON:0035805	60.36	gold quality
saphenous vein	UBERON:0007318	60.24	gold quality
mammary gland	UBERON:0001911	59.34	gold quality
thoracic mammary gland	UBERON:0005200	59.18	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-HCAD-36	yes	8012.88
E-HCAD-29	yes	6063.44
E-MTAB-7052	yes	4873.28
E-MTAB-6308	yes	4056.81
E-CURD-122	yes	65.66
E-MTAB-8142	yes	45.81
E-CURD-46	yes	21.42
E-CURD-114	yes	20.73
E-MTAB-9801	yes	5.80
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

58 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Adipose tissue	tissue	19.5
Cervix	tissue	19.4
Bone marrow	tissue	14.9
Urinary bladder	tissue	14.8
Appendix	tissue	13.6
Rectum	tissue	8.6
Lung	tissue	8.4
Stomach 1	tissue	6.7
Gallbladder	tissue	6.5
Thalamus	tissue	5.0
Cerebral cortex	tissue	4.0
Colon	tissue	3.8
Liver	tissue	3.7
Thymus	tissue	1.9
Salivary gland	tissue	1.7
Smooth muscle	tissue	1.5
Breast	tissue	1.3
Pancreas	tissue	1.3
Tongue	tissue	1.0
Small intestine	tissue	1.0
Vagina	tissue	0.9
Prostate	tissue	0.9
Esophagus	tissue	0.8
Endometrium 1	tissue	0.7
Amygdala	tissue	0.7
Fallopian tube	tissue	0.7
Lymph node	tissue	0.6
Hypothalamus	tissue	0.6
Placenta	tissue	0.6
Spleen	tissue	0.6
Duodenum	tissue	0.6
Tonsil	tissue	0.6
Pituitary gland	tissue	0.5
Choroid plexus	tissue	0.5
Midbrain	tissue	0.5
Medulla oblongata	tissue	0.5
Adrenal gland	tissue	0.5
Pons	tissue	0.4
Kidney	tissue	0.4
Heart muscle	tissue	0.3
Spinal cord	tissue	0.3
Hippocampal formation	tissue	0.3
Testis	tissue	0.2
Seminal vesicle	tissue	0.2
Basal ganglia	tissue	0.2
Substantia nigra	tissue	0.2
Thyroid gland	tissue	0.2
Hippocampus	tissue	0.2
Skin 1	tissue	0.1
Retina	tissue	0.1
Ovary	tissue	0.1
Parathyroid gland	tissue	0.1
Putamen	tissue	0.1
Nucleus accumbens	tissue	0.1
Locus coeruleus	tissue	0.1
Postcentral gyrus	tissue	0.1
Retrosplenial cortex	tissue	0.1
Occipital cortex	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 122; highest nTPM — Anterior thalamic nucleus, ventral (5.0), Area parastriata, superior (4.0), Blood vessel (2.1), Angular gyrus (white matter) (0.6), Frontal operculum (0.6).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF4, FOXL2, HSF1, NFKB1, PPARG, RELA, XBP1

miRNA regulators (miRDB)

Targeting CXCL3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 42 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258

Functional genomics

gnomAD constraint: pLI 0.000858, LOEUF 1.38, missense Z -0.841 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000296026 — one region, missense o/e 1.07.

Literature-anchored findings (GeneRIF, showing 35)

• CXCL3 displays antimicrobial activity against E. coli and S. aureus. (PMID:12949249)
• demonstrates, for the first time, that BIRC3 (anti-apoptotic protein), COL3A1 (matrix protein synthesis), and CXCL3 (chemokine) were up-regulated in the thrombin-stimulated human umbilical vein endothelial cells (PMID:16356540)
• GRO-gamma is a promising candidate for Th2-associated glomerular permeability factor in minimal change disease. (PMID:17389786)
• Inhibition of ERK phosphorylation decreased expression of GRO3. (PMID:17466952)
• Report gonadotropin-releasing hormone-regulated CXCL3 expression in human placentation. (PMID:19369450)
• propose that chemokines belonging to the CXC family could play an important role in the etiology of tendon xanthoma (TX), with CXCL3 being a possible biological marker of onset and development of TX (PMID:19448742)
• overexpression of CXCL13 in the intestine during inflammatory conditions favors mobilization of B cells and of LTi and NK cells with immunomodulatory and reparative functions. (PMID:19741597)
• A significantly increased expression of GRO-2, GRO-3, and IL-8 in colon carcinoma as compared to normal tissue, is reported. (PMID:20162422)
• Data show that mesenchymal stem cells (MSCs) directly regulate T cell proliferation by induction of CXCL3 chemokine and its receptor, CXCR2 on the surface in T cells. (PMID:23023221)
• This study demonistrated that CXCL1, CXCL2, CXCL3, CXCL8, and CXCL11, absent from normal muscle fibers, were induced in DMD myofibers. (PMID:23225384)
• secreted growth-regulated oncogene chemokines, specifically GRO-gamma, in human Mesenchymal stromal cell-conditioned media have an effect on the differentiation and the function of human monocyte-derived dendritic cells. (PMID:23589610)
• our results demonstrate the diverse mechanisms by which CXCL2 and CXCL3 mediate normal and asthmatic airway smooth muscle cell migration (PMID:23904157)
• results support a functional role of CXCL3 in breast cancer metastasis and as a viable target for cancer therapy (PMID:24605943)
• Our findings suggest that CXCL3 and its receptor CXCR2 are overexpressed in prostate cancer cells, prostate epithelial cells and prostate cancer tissues, which may play multiple roles in prostate cancer progression and metastasis. (PMID:26837773)
• Exogenous CXCL3 induced Erk1/2 and ETS1 phosphorylation and promoted CD133 expression. (PMID:27255419)
• This report demonstrates that Cxcl3 induces the migration of normal and neoplastic cerebellar precursor cells (GCPs) from the surface to the internal part of the cerebellum, a region where the GCPs differentiate, thus exiting the neoplastic program. In this way Cxcl3 counteracts the growth of medulloblastoma, tumor of the cerebellum originating from the GCPs. (PMID:28018222)
• The studies revealed that, although overall structural and oligomerization features of CXCL3 and CXCL2 are similar, prominent differences were observed in their surface characteristics, thus implicating a functional divergence. (PMID:28928065)
• CXCL3 exerts its carcinogenic potential by directly and/or indirectly regulating the downstream signaling pathways and the expression of transcription factors in PCa. (PMID:29524043)
• Migration, invasion, proliferation and tube-formation capability of HTR-8/SVneo trophoblast cells transfected with siRNA-CXCL3 were suppressed by down-regulation of CXCL3, while those behaviors of HTR-8/SVneo cells transfected with pEZ-CXCL3 were enhanced by upregulation of CXCL3. Nevertheless, the apoptosis of HTR-8/SVneo cells was not affected by either siRNA or overexpression plasmid. (PMID:29884302)
• hydrophobic pocket is in the vicinity of GAG binding region of CXCL3, a molecular determinant in leukocyte trafficking (PMID:30528777)
• Study demonstrated that CXCL3 is not only considerably upregulated in colon cancer (CC) tumor tissue but also has potential diagnostic value in patients with CC. Survival analysis suggested that CXCL3 may serve as a potential prognostic biomarker in CC. (PMID:31545503)
• CXCL3 overexpression promotes the tumorigenic potential of uterine cervical cancer cells via the MAPK/ERK pathway. (PMID:31667838)
• Gene expression and methylation profiles identified CXCL3 and CXCL8 as key genes for diagnosis and prognosis of colon adenocarcinoma. (PMID:31709538)
• Relationship between polymorphisms of CXCL3 gene and preeclampsia. (PMID:31931644)
• CX3 CL1 promotes tumour cell by inducing tyrosine phosphorylation of cortactin in lung cancer. (PMID:33191645)
• Inflammatory cell-derived CXCL3 promotes pancreatic cancer metastasis through a novel myofibroblast-hijacked cancer escape mechanism. (PMID:33568427)
• Expression levels of chemokine (C-X-C motif) ligands CXCL1 and CXCL3 as prognostic biomarkers in rectal adenocarcinoma: evidence from Gene Expression Omnibus (GEO) analyses. (PMID:34269159)
• CXCL3 overexpression affects the malignant behavior of oral squamous cell carcinoma cells via the MAPK signaling pathway. (PMID:34392586)
• Clinical significance and biological functions of chemokine CXCL3 in head and neck squamous cell carcinoma. (PMID:34870709)
• Tumor suppressive lncRNA MEG3 binds to EZH2 and enhances CXCL3 methylation in gallbladder cancer. (PMID:35188401)
• Plasma CXCL3 Levels Are Associated with Tumor Progression and an Unfavorable Colorectal Cancer Prognosis. (PMID:35664357)
• Knockdown of CXCL3-inhibited apoptosis and inflammation in lipopolysaccharide-treated BEAS-2B and HPAEC through inactivating MAPKs pathway. (PMID:35789398)
• Chronic restraint stress promotes the tumorigenic potential of oral squamous cell carcinoma cells by reprogramming fatty acid metabolism via CXCL3 mediated Wnt/beta-catenin pathway. (PMID:36343679)
• Elevated expression of CXCL3 in colon cancer promotes malignant behaviors of tumor cells in an ERK-dependent manner. (PMID:38031087)
• Comprehensive analysis of the clinical and biological significances for chemokine CXCL3 in cholangiocarcinoma. (PMID:38489741)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cxcl3	ENSMUSG00000029379
mus_musculus	Cxcl1	ENSMUSG00000029380
mus_musculus	Cxcl2	ENSMUSG00000058427
rattus_norvegicus	Cxcl2	ENSRNOG00000002792
rattus_norvegicus	Cxcl1	ENSRNOG00000002802
rattus_norvegicus	Cxcl3	ENSRNOG00000028043

Paralogs (12): CXCL2 (ENSG00000081041), PF4V1 (ENSG00000109272), CXCL6 (ENSG00000124875), CXCL9 (ENSG00000138755), CXCL13 (ENSG00000156234), CXCL5 (ENSG00000163735), PPBP (ENSG00000163736), PF4 (ENSG00000163737), CXCL1 (ENSG00000163739), CXCL10 (ENSG00000169245), CXCL11 (ENSG00000169248), CXCL8 (ENSG00000169429)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:3037818) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 7 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased bone mineral density	1
increased monocyte cell number	1
enlarged lymph nodes	1
hyperactivity	1
abnormal eye morphology	1
abnormal lymph node morphology	1
decreased bone mineral content	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca mulatta	P67813	100.0%	Diamond
Macaca nemestrina	P67814	100.0%	Diamond
Bos taurus	O46677	98.1%	Diamond
Oryctolagus cuniculus	P47854	98.1%	Diamond
Ovis aries	P36925	96.0%	Diamond
Cercocebus atys	P46653	96.0%	Diamond
Xenopus tropicalis	Q5EBF6	95.7%	Diamond
Xenopus laevis	Q8UUJ9	95.7%	Diamond
Canis lupus familiaris	P41324	91.1%	Diamond
Sus scrofa	P26894	90.9%	Diamond
Tursiops truncatus	Q7YRB5	89.1%	Diamond
Felis catus	Q9XSX5	89.0%	Diamond
Cricetulus griseus	P09340	84.4%	Diamond
Equus caballus	Q8MIN2	81.7%	Diamond
Cavia porcellus	P49113	72.3%	Diamond
Gallus gallus	P08317	56.3%	Diamond
Danio rerio	A0A0R4INB9	50.6%	Diamond
Marek’s disease herpesvirus type 1 strain MD5	Q77MQ6	46.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CXCL3-AS1	ncRNA	105377275
PPBP	protein-coding	5473
CXCL5	protein-coding	6374
CXCL2	protein-coding	2920
PF4	protein-coding	5196

Protein

Protein identifiers

C-X-C motif chemokine 3 — P19876 (reviewed: P19876)

Alternative names: GRO-gamma(1-73), Growth-regulated protein gamma, Macrophage inflammatory protein 2-beta

All UniProt accessions (1): P19876

UniProt curated annotations — full annotation on UniProt →

Function. Ligand for CXCR2. Has chemotactic activity for neutrophils. May play a role in inflammation and exert its effects on endothelial cells in an autocrine fashion. In vitro, the processed form GRO-gamma(5-73) shows a fivefold higher chemotactic activity for neutrophilic granulocytes.

Subcellular location. Secreted.

Post-translational modifications. N-terminal processed form GRO-gamma(5-73) is produced by proteolytic cleavage after secretion from peripheral blood monocytes.

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

RefSeq proteins (1): NP_002081* (*=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 (13 total): strand 4, chain 2, helix 2, disulfide bond 2, signal peptide 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
8XX3	Structure of CXCR2 bound to CXCL3 (CXCR2-CXCL3-Go Full map)	ELECTRON MICROSCOPY	3.38
8XWF	Structure of CXCR2 bound to CXCL3 (Ligand-receptor focused map)	ELECTRON MICROSCOPY	3.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19876-F1	82.50	0.50

Antibody-complex structures (SAbDab)

1 antibodies co-crystallized with this protein: 8XX3

Human Protein Atlas

Protein class: Predicted secreted proteins, Plasma proteins

Protein evidence: Evidence at protein level

Functional residue map

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

Disulfide bonds (2)

Type	Positions
Disulfide bond	43–69, 45–85

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 8; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-380108	Chemokine receptors bind chemokines	curated
R-HSA-418594	G alpha (i) signalling events	curated
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-500792	GPCR ligand binding	—
R-HSA-375276	Peptide ligand-binding receptors	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—

MSigDB gene sets: 420 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, HALMOS_CEBPA_TARGETS_UP, SOUCEK_MYC_TARGETS, GAURNIER_PSMD4_TARGETS, HNF1_Q6, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN

GO Biological Process (6): inflammatory response (GO:0006954), immune response (GO:0006955), neutrophil chemotaxis (GO:0030593), chemotaxis (GO:0006935), defense response (GO:0006952), signal transduction (GO:0007165)

GO Molecular Function (2): chemokine activity (GO:0008009), cytokine activity (GO:0005125)

GO Cellular Component (1): extracellular region (GO:0005576)

Reactome top-level categories

6 top-level categories:

Category	Pathways
Signaling by GPCR	2
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

18 GO namespaces:

Category	Terms
defense response	1
immune system process	1
response to stimulus	1
granulocyte chemotaxis	1
neutrophil migration	1
response to chemical	1
taxis	1
response to stress	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cytokine activity	1
chemokine receptor binding	1
cell chemotaxis	1
receptor ligand activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

showing 16 of 1,522 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CXCL3	CXCL10	P02778	904
CXCL3	CXCL11	O14625	901
CXCL3	CXCR2	P25025	823
CXCL3	CXCL14	O95715	776
CXCL3	CXCR1	P25024	756
CXCL3	CCL18	P55774	721
CXCL3	CCL20	P78556	716
CXCL3	CXCL12	P48061	710
CXCL3	CCL17	Q92583	706
CXCL3	CCL22	O00626	704
CXCL3	CCL19	Q99731	700
CXCL3	CCL2	P13500	651
CXCL3	CXCL13	O43927	612
CXCL3	IL1B	P01584	606
CXCL3	IL6	P05231	606
CXCL3	CCL3	P10147	606

IntAct

Human interaction partners of CXCL3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
CCL11	direct interaction	0.440	1
CXCL5	direct interaction	0.440	1
CXCL6	direct interaction	0.440	1
XCL2	direct interaction	0.440	1
CXCL1	association	0.350	1
IFI30	association	0.350	1

BioGRID (12 interactions; top human partners by supporting records): CXCL2 (Affinity Capture-MS; 2 records), BIRC2 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), CCL11 (Reconstituted Complex), CXCL1 (Affinity Capture-MS), CXCL5 (Reconstituted Complex), CXCL6 (Reconstituted Complex), IFI30 (Affinity Capture-MS), TIMP2 (Proximity Label-MS), TRAF2 (Affinity Capture-MS), XCL2 (Reconstituted Complex)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
CXCL3	“up-regulates activity”	CXCR2	binding

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
CXCR2	ligand	Signaling by Chemokines

Disease & clinical

Genetic variants

Variant evidence for CXCL3: 19 ClinVar records (1 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	14
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
148549	GRCh38/hg38 4q13.2-13.3(chr4:67799665-74240920)x1	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CXCL3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 183):

Position(s)	Effect	Δscore	Sites
4:74038177	acceptor_gain	1.0000
4:74038177–74038178	acceptor_loss	1.0000	5
4:74038414–74038415	acceptor_loss	1.0000	5
4:74038510–74038511	donor_loss	1.0000	4
4:74038088	donor_loss	0.9900	2
4:74038091–74038092	donor_loss	0.9900	5
4:74038288–74038289	donor_loss	0.9900	6
4:74038414	acceptor_loss	0.9900
4:74038511	donor_loss	0.9900
4:74037278–74037279	acceptor_loss	0.9800	5

AlphaMissense

109 missense substitutions predicted likely pathogenic (of 680 scored), across 34 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
C69	7	0.940	0.967
C85	7	0.933	0.965
C43	7	0.915	0.956
C45	7	0.905	0.962
E73	6	0.891	0.940
V74	5	0.855	0.971
A76	5	0.748	0.991
R42	5	0.670	0.750
L86	4	0.881	0.976
G66	4	0.766	0.806
K79	4	0.766	0.875
I57	3	0.967	0.969
I52	3	0.901	0.912
V60	3	0.848	0.951
G81	3	0.804	0.915
I96	3	0.786	0.822
K55	3	0.699	0.704
N87	3	0.687	0.737
N80	3	0.660	0.662
P88	3	0.630	0.678

HPA cancer prognostics

RNA cancer specificity: Group enriched (Colon Adenocarcinoma, Rectum Adenocarcinoma, Stomach Adenocarcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	7.47e-05

Disease associations

OMIM: gene MIM:139111 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST001725_78	Inflammatory bowel disease	3e-8
GCST002826_3	Urate levels (BMI interaction)	3e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, increases abundance, increases expression, affects expression	7
sodium arsenite	decreases reaction, increases expression	6
Lipopolysaccharides	affects cotreatment, decreases reaction, increases expression, affects expression, affects response to substance	4
Silicon Dioxide	increases expression	4
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	3
Cannabidiol	decreases reaction, increases expression	3
Methotrexate	decreases expression, increases expression	3
Valproic Acid	affects expression, decreases methylation, increases expression	3
Asbestos, Crocidolite	increases expression	3
1-nitropyrene	increases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Air Pollutants	increases abundance, increases expression	2
Cadmium	increases expression	2
Dexamethasone	decreases expression, affects cotreatment	2
Estradiol	affects expression, decreases expression	2
Piroxicam	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
huai qi huang	decreases reaction, increases expression	1
Glupearl 19S	increases expression	1
bisphenol F	affects cotreatment, decreases expression	1
Asian ginseng	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	affects expression	1
lead acetate	increases expression	1
primycin	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.