CCL23

Summary

CCL23 (C-C motif chemokine ligand 23, HGNC:10622) is a protein-coding gene on chromosome 17q12, encoding C-C motif chemokine 23 (P55773). Shows chemotactic activity for monocytes, resting T-lymphocytes, and neutrophils, but not for activated lymphocytes.

This gene is one of several chemokine genes clustered on the q-arm of chromosome 17. Chemokines form a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of the N-terminal cysteine residues of the mature peptide. This chemokine, a member of the CC subfamily, displays chemotactic activity on resting T lymphocytes and monocytes, lower activity on neutrophils and no activity on activated T lymphocytes. The protein is also a strong suppressor of colony formation by a multipotential hematopoietic progenitor cell line. In addition, the product of this gene is a potent agonist of the chemokine (C-C motif) receptor 1. Alternative splicing results in multiple transcript variants that encode different isoforms.

Source: NCBI Gene 6368 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 31 total
• MANE Select transcript: NM_005064

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10622
Approved symbol	CCL23
Name	C-C motif chemokine ligand 23
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	Ckb-8, MPIF-1, MIP-3, CKb8
Ensembl gene	ENSG00000274736
Ensembl biotype	protein_coding
OMIM	602494
Entrez	6368

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000612516, ENST00000613876, ENST00000615050

RefSeq mRNA: 2 — MANE Select: NM_005064 NM_005064, NM_145898

CCDS: CCDS11305, CCDS59282

Canonical transcript exons

ENST00000610342 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 115 present calls, max score 95.51.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6668 / max 96.9827, expressed in 144 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165424	0.3414	97
165425	0.3254	94

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.51	gold quality
right lung	UBERON:0002167	86.02	gold quality
upper lobe of left lung	UBERON:0008952	84.44	gold quality
vermiform appendix	UBERON:0001154	83.30	gold quality
left uterine tube	UBERON:0001303	82.52	gold quality
ectocervix	UBERON:0012249	81.94	gold quality
spleen	UBERON:0002106	81.53	gold quality
rectum	UBERON:0001052	81.01	gold quality
endocervix	UBERON:0000458	80.57	gold quality
mucosa of stomach	UBERON:0001199	80.19	gold quality
smooth muscle tissue	UBERON:0001135	79.46	gold quality
body of uterus	UBERON:0009853	79.42	gold quality
myometrium	UBERON:0001296	79.34	gold quality
mucosa of transverse colon	UBERON:0004991	79.03	gold quality
lung	UBERON:0002048	77.94	gold quality
right adrenal gland	UBERON:0001233	77.45	gold quality
right lobe of liver	UBERON:0001114	77.39	gold quality
vagina	UBERON:0000996	76.47	gold quality
liver	UBERON:0002107	75.77	gold quality
uterine cervix	UBERON:0000002	75.40	gold quality
right adrenal gland cortex	UBERON:0035827	75.39	gold quality
left adrenal gland	UBERON:0001234	75.16	gold quality
omental fat pad	UBERON:0010414	75.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	74.97	gold quality
adipose tissue	UBERON:0001013	74.70	gold quality
subcutaneous adipose tissue	UBERON:0002190	74.43	gold quality
gall bladder	UBERON:0002110	74.11	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.79	gold quality
left adrenal gland cortex	UBERON:0035825	73.71	gold quality
fallopian tube	UBERON:0003889	73.57	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10137	yes	927.44
E-ANND-3	yes	7.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, STAT6

miRNA regulators (miRDB)

22 targeting CCL23, 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-5692A	100.00	74.40	6850
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-219B-3P	97.31	66.96	672
HSA-MIR-3657	96.33	66.29	608

Literature-anchored findings (GeneRIF, showing 24)

• CCL23 promoted chemotactic migration and differentiation of endothelial cells, and neovascularization in the chick chorioallantoic membrane (PMID:15927850)
• May play a direct role in angiogenesis via upregulation of matrix metalloproteinase (MMP)-2 expression. (PMID:16378600)
• Collectively, these data suggest a link between the inducible phenotype of CCL23 expression in monocytes by the prototype Th2 molecule pair IL-4/STAT6 and the increased number of CCL23-expressing cells in skin of atopic dermatitis patients. (PMID:17371990)
• A peptide ligand termed SHAAGtide is cleaved from CCL23; is itself an attractant of monocytes and neutrophils in vitro; recruits leukocytes in vivo; is more potent than other natural agents with activity for FPRL1; receives authors’ designation “CCR12.” (PMID:17513790)
• This protein may participate in the malignant progression of certain human cancer cells that overexpress ErbB2 through the transactivation of ErbB2 tyrosine kinase. (PMID:18258606)
• CCL23, M-CSF, TNFRSF9, TNF-alpha, and CXCL13 are predictive of rheumatoid arthritis disease activity and may be useful in the definition of disease subphenotypes and in the measurement of response to therapy in clinical studies. (PMID:18668547)
• these findings suggest that CCL23 results in up-regulation of KDR/flk-1 receptor gene transcription and protein expression and that KDR/Flk-1 up-regulation induced by CCL23 may contribute to potentiation of VEGF action in angiogenesis. (PMID:19265684)
• CKbeta8 transduces the chemotaxis signal through the G(i)/G(o) protein, phospholipase C, protein kinase C delta and NF-kappaB. (PMID:19951712)
• CKbeta8- and CKbeta8-1-induced activation of ERK1/2 is mediated by the G(i)/G(o) protein, PLC, and PKCdelta. (PMID:20097574)
• independently associated with coronary atherosclerosis (PMID:20187767)
• Patients with systemic sclerosis who had elevated CCL23 levels had shorter disease duration, and a higher frequency of pulmonary arterial hypertension. Serum CCL23 level was increased in early phase of disease and could be a marker for disease activity. (PMID:20824279)
• The role of KLF6 and PPAR-gamma in MIP-3alpha transcriptional regulation, was determined. (PMID:21109018)
• Overproduction of CCL23 in nasal polyps might contribute to the pathogenesis of eosinophilic chronic rhinosinusitis with nasal polyps (PMID:21497884)
• Fresh eosinophils contained trace amounts of CCL23 protein. CCL23 was significantly released into the supernatant when the eosinophils were stimulated with GM-CSF or IL-5 but not with IFN-gamma or immobilized sIgA. (PMID:21646793)
• Data show CCL23 stimulates chemotaxis of human THP-1 monocytes and enhances release of MMP-2, and suggest it plays a role in atherogenesis. (PMID:21656154)
• ADAMTS 8, CCL23, and TNFSF15 are implicated in anti-angiogenic activities (PMID:24384427)
• The coexistence of diabetes and oxidative stress independently affected CCL23 levels, while the presence of Cardiovascular disease and inflammation had no impact on its concentrations. (PMID:24995525)
• CCL23 is posttranslationally modified by trypsin-like serine proteases and CCL23(47-117) might be a major active form of CCL23 in nasal polyps with chronic rhinosinusitis. (PMID:26560043)
• The low expression of CCL23 in hepatocellular carcinoma (HCC) tissue is not conducive to the development of anti-tumor immune defense in HCC patients and significantly shortens the survival of HCC patients. (PMID:31814567)
• CCL23: A Chemokine Associated with Progression from Mild Cognitive Impairment to Alzheimer’s Disease. (PMID:31958084)
• CCL23 suppresses liver cancer progression through the CCR1/AKT/ESR1 feedback loop. (PMID:34050704)
• Inhibitory effect of CC chemokine ligand 23 (CCL23)/ transcription factor activating enhancer binding protein 4 (TFAP4) on cell proliferation, invasion and angiogenesis in hepatocellular carcinoma. (PMID:35001801)
• Macrophage-derived CCL23 upregulates expression of T-cell exhaustion markers in ovarian cancer. (PMID:35750747)
• Delayed CCL23 response is associated with poor outcomes after cardiac arrest. (PMID:38325139)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccl35.2	ENSDARG00000070378
danio_rerio	ccl35.1	ENSDARG00000103466
mus_musculus	Ccl6	ENSMUSG00000018927
mus_musculus	Ccl9	ENSMUSG00000019122
rattus_norvegicus	Ccl9	ENSRNOG00000028548

Paralogs (26): CX3CL1 (ENSG00000006210), CCL26 (ENSG00000006606), CCL22 (ENSG00000102962), CCL17 (ENSG00000102970), CCL24 (ENSG00000106178), CCL7 (ENSG00000108688), CCL2 (ENSG00000108691), CCL8 (ENSG00000108700), CCL1 (ENSG00000108702), CCL20 (ENSG00000115009), CCL25 (ENSG00000131142), CCL21 (ENSG00000137077), XCL1 (ENSG00000143184), XCL2 (ENSG00000143185), CCL11 (ENSG00000172156), CCL19 (ENSG00000172724), CCL13 (ENSG00000181374), CCL5 (ENSG00000271503), CCL16 (ENSG00000275152), CCL4 (ENSG00000275302), CCL18 (ENSG00000275385), CCL15 (ENSG00000275718), CCL4L2 (ENSG00000276070), CCL3L3 (ENSG00000276085), CCL14 (ENSG00000276409), CCL3 (ENSG00000277632)

Protein

Protein identifiers

C-C motif chemokine 23 — P55773 (reviewed: P55773)

Alternative names: CK-beta-8, Macrophage inflammatory protein 3, Myeloid progenitor inhibitory factor 1, Small-inducible cytokine A23

All UniProt accessions (2): P55773, A0A087WV09

UniProt curated annotations — full annotation on UniProt →

Function. Shows chemotactic activity for monocytes, resting T-lymphocytes, and neutrophils, but not for activated lymphocytes. Inhibits proliferation of myeloid progenitor cells in colony formation assays. This protein can bind heparin. Binds CCR1. CCL23(19-99), CCL23(22-99), CCL23(27-99), CCL23(30-99) are more potent chemoattractants than CCL23.

Subcellular location. Secreted.

Tissue specificity. High levels in adult lung, liver, skeletal muscle and pancreas. Moderate levels in fetal liver, adult bone marrow and placenta. The short form is the major species and the longer form was detected only in very low abundance. CCL23(19-99), CCL23(22-99), CCL23(27-99), CCL23(30-99) are found in high levels in synovial fluids from rheumatoid patients.

Post-translational modifications. The N-terminal is proteolytically cleaved by proteases associated with inflammatory responses. The processed forms, CCL23(19-99), CCL23(22-99), CCL23(27-99) and CCL23(30-99) exhibit increase in CCR1-mediated signaling and chemotaxis assays in vitro.

Similarity. Belongs to the intercrine beta (chemokine CC) family.

Isoforms (2)

UniProt ID	Names	Canonical?
P55773-1	Short, CKB-8	yes
P55773-2	Long, CKB-8-1

RefSeq proteins (2): NP_005055, NP_665905 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000827	Chemokine_CC_CS	Conserved_site
IPR001811	Chemokine_IL8-like_dom	Domain
IPR036048	Interleukin_8-like_sf	Homologous_superfamily
IPR039809	Chemokine_b/g/d	Family

Pfam: PF00048

UniProt features (20 total): chain 5, strand 5, disulfide bond 3, helix 2, signal peptide 1, sequence variant 1, sequence conflict 1, turn 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1G91	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55773-F1	76.75	0.56

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 (3): 54–78, 55–94, 65–105

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-416476	G alpha (q) signalling events
R-HSA-418594	G alpha (i) signalling events
R-HSA-444473	Formyl peptide receptors bind formyl peptides and many other ligands

MSigDB gene sets: 170 (showing top): MODULE_92, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, MODULE_64, GAURNIER_PSMD4_TARGETS, HUMMERICH_SKIN_CANCER_PROGRESSION_UP, GOBP_CELL_CELL_SIGNALING, GOBP_LEUKOCYTE_CHEMOTAXIS, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_TAXIS

GO Biological Process (13): monocyte chemotaxis (GO:0002548), intracellular calcium ion homeostasis (GO:0006874), chemotaxis (GO:0006935), inflammatory response (GO:0006954), immune response (GO:0006955), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), cell-cell signaling (GO:0007267), negative regulation of cell population proliferation (GO:0008285), positive regulation of cell migration (GO:0030335), cell chemotaxis (GO:0060326), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), chemokine-mediated signaling pathway (GO:0070098)

GO Molecular Function (6): chemokine activity (GO:0008009), heparin binding (GO:0008201), CCR1 chemokine receptor binding (GO:0031726), CCR chemokine receptor binding (GO:0048020), cytokine activity (GO:0005125), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR downstream signalling	2
Peptide ligand-binding receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	2
signaling	2
cell migration	2
chemokine receptor binding	2
leukocyte chemotaxis	1
mononuclear cell migration	1
myeloid leukocyte migration	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
response to chemical	1
taxis	1
defense response	1
immune system process	1
response to stimulus	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
regulation of cell migration	1
positive regulation of cell motility	1
chemotaxis	1
cellular response to chemical stimulus	1
antimicrobial humoral response	1
G protein-coupled receptor signaling pathway	1
cytokine-mediated signaling pathway	1
cellular response to chemokine	1
cytokine activity	1
cell chemotaxis	1
glycosaminoglycan binding	1
sulfur compound binding	1
CCR chemokine receptor binding	1
receptor ligand activity	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1016 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCL23	CCR1	P32246	992
CCL23	CCL24	O00175	861
CCL23	CCR6	P51684	859
CCL23	CCL7	P80098	827
CCL23	CCL2	P13500	781
CCL23	CCL20	P78556	770
CCL23	CCL25	O15444	741
CCL23	CCL27	Q9Y4X3	727
CCL23	CCR3	P51677	727
CCL23	HBS1L	Q9Y450	688
CCL23	CCRL2	O00421	668
CCL23	TFAP4	Q01664	665
CCL23	HBG1	P02096	665
CCL23	CCL22	O00626	661
CCL23	CCR7	P32248	661

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CCL23	IDE	psi-mi:“MI:0915”(physical association)	0.590
CCL23	CCL21	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (5): MUCL1 (Affinity Capture-MS), IDE (Affinity Capture-MS), CCR1 (Reconstituted Complex), CCL21 (Reconstituted Complex), IDE (Affinity Capture-MS)

ESM2 similar proteins: A8YXX7, B4X8D9, O46655, O75711, O76095, O77049, O88745, O88823, O88824, P01186, P01359, P04155, P08163, P08833, P0CW02, P18406, P21743, P21744, P22934, P24593, P24594, P25118, P35455, P47876, P47879, P55773, Q03191, Q03403, Q05717, Q07079, Q07654, Q08423, Q16663, Q28985, Q29183, Q62395, Q63467, Q66IA6, Q6DGP8, Q6Q484

Diamond homologs: F5HET8, O00175, O00585, O00626, O55145, O88430, O97919, P10147, P10148, P10855, P13236, P13500, P13501, P14097, P14844, P16619, P27784, P28291, P28292, P30882, P42831, P46632, P47993, P49873, P50229, P50230, P50231, P51670, P51671, P52203, P55773, P55774, P61274, P61275, P78423, P80075, P80098, P80343, P82943, P97272

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

554 predictions. Top by Δscore:

Variant	Effect	Δscore
17:36013304:GGAAG:G	acceptor_gain	1.0000
17:36013305:GAAG:G	acceptor_gain	1.0000
17:36013306:AAG:A	acceptor_gain	1.0000
17:36013307:AG:A	acceptor_gain	1.0000
17:36013309:C:CC	acceptor_gain	1.0000
17:36014332:A:AC	donor_gain	1.0000
17:36014332:ACTGT:A	donor_gain	1.0000
17:36014333:C:CT	donor_gain	1.0000
17:36014333:CT:C	donor_gain	1.0000
17:36014333:CTGT:C	donor_gain	1.0000
17:36014333:CTGTC:C	donor_gain	1.0000
17:36014394:C:CC	acceptor_gain	1.0000
17:36013306:AAGC:A	acceptor_loss	0.9900
17:36013309:C:G	acceptor_loss	0.9900
17:36013310:T:C	acceptor_loss	0.9900
17:36013317:C:CT	acceptor_gain	0.9900
17:36013318:A:T	acceptor_gain	0.9900
17:36013742:A:AC	donor_gain	0.9900
17:36013743:C:CC	donor_gain	0.9900
17:36013789:T:A	donor_gain	0.9900
17:36014321:T:C	donor_gain	0.9900
17:36014328:ACTT:A	donor_loss	0.9900
17:36014329:CTTAC:C	donor_loss	0.9900
17:36014330:TTACT:T	donor_loss	0.9900
17:36014333:CTG:C	donor_gain	0.9900
17:36014391:CAT:C	acceptor_gain	0.9900
17:36014392:AT:A	acceptor_gain	0.9900
17:36014394:CTGGA:C	acceptor_loss	0.9900
17:36014404:C:CT	acceptor_gain	0.9900
17:36016404:A:AC	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000239229 (17:36012627 C>G), RS1000249099 (17:36016359 T>C), RS1001116162 (17:36015277 C>G), RS1001253879 (17:36015020 G>A,C), RS1001437412 (17:36017132 A>G), RS1002121881 (17:36013966 G>A), RS1002461987 (17:36019516 T>G), RS1003415589 (17:36018495 C>A), RS1003584315 (17:36012765 A>C,T), RS1003645 (17:36013244 T>A,C), RS1003876894 (17:36018162 G>C), RS1004443440 (17:36019901 C>A,G,T), RS1004471309 (17:36016168 A>G), RS1005107 (17:36013552 C>A,T), RS1005453823 (17:36018544 C>T)

Disease associations

OMIM: gene MIM:602494 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002113_4	Pulmonary function	3.000000e-07
GCST006585_2209	Blood protein levels	4.000000e-41
GCST006622_12	Neonatal cytokine/chemokine levels (fetal genetic effect)	3.000000e-100

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004713	FEV/FVC ratio
EFO:0004747	protein measurement
EFO:0007959	fetal genotype effect measurement
EFO:0009417	CCL23 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
lipopolysaccharide, E. coli O26-B6	decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	increases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	increases expression	1
Tretinoin	increases expression	1
Medroxyprogesterone Acetate	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Nanotubes, Carbon	increases expression	1

Clinical trials (associated diseases)

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