CCL14

Summary

CCL14 (C-C motif chemokine ligand 14, HGNC:10612) is a protein-coding gene on chromosome 17q12, encoding C-C motif chemokine 14 (Q16627). Has weak activities on human monocytes and acts via receptors that also recognize MIP-1 alpha.

This gene, chemokine (C-C motif) ligand 14, is one of several CC cytokine genes clustered on 17q11.2. The CC cytokines are secreted proteins characterized by two adjacent cysteines. The cytokine encoded by this gene induces changes in intracellular calcium concentration and enzyme release in monocytes. Multiple transcript variants encoding different isoforms have been found for this gene. Read-through transcripts are also expressed that include exons from the upstream cytokine gene, chemokine (C-C motif) ligand 15, and are represented as GeneID: 348249.

Source: NCBI Gene 6358 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 16 total
• MANE Select transcript: NM_032963

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10612
Approved symbol	CCL14
Name	C-C motif chemokine ligand 14
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	HCC-1, HCC-3, NCC-2, SCYL2, CKb1, MCIF
Ensembl gene	ENSG00000276409
Ensembl biotype	protein_coding
OMIM	601392
Entrez	6358

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000614009, ENST00000618404, ENST00000620991, ENST00000622526, ENST00000905906

RefSeq mRNA: 2 — MANE Select: NM_032963 NM_032962, NM_032963

CCDS: CCDS32624, CCDS45652

Canonical transcript exons

ENST00000618404 — 3 exons

Exon	Start	End
ENSE00003716001	35984338	35984452
ENSE00003726139	35986571	35986729
ENSE00003751757	35983288	35983888

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 99.50.

FANTOM5 (CAGE): breadth broad, TPM avg 16.4817 / max 1228.4374, expressed in 253 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165418	16.4697	253
165417	0.0119	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	99.50	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.18	gold quality
left uterine tube	UBERON:0001303	99.15	gold quality
adipose tissue	UBERON:0001013	99.12	gold quality
omental fat pad	UBERON:0010414	99.05	gold quality
thoracic mammary gland	UBERON:0005200	98.98	gold quality
mucosa of stomach	UBERON:0001199	98.78	gold quality
endocervix	UBERON:0000458	98.66	gold quality
body of uterus	UBERON:0009853	98.52	gold quality
myometrium	UBERON:0001296	98.47	gold quality
smooth muscle tissue	UBERON:0001135	98.23	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.08	gold quality
left coronary artery	UBERON:0001626	97.96	gold quality
ectocervix	UBERON:0012249	97.68	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.66	gold quality
right coronary artery	UBERON:0001625	97.63	gold quality
gall bladder	UBERON:0002110	97.63	gold quality
tibial nerve	UBERON:0001323	97.61	gold quality
lower esophagus	UBERON:0013473	97.58	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.51	gold quality
vagina	UBERON:0000996	97.31	gold quality
right lobe of thyroid gland	UBERON:0001119	97.11	gold quality
left lobe of thyroid gland	UBERON:0001120	96.87	gold quality
fallopian tube	UBERON:0003889	96.84	gold quality
right adrenal gland cortex	UBERON:0035827	96.84	gold quality
fundus of stomach	UBERON:0001160	96.63	gold quality
descending thoracic aorta	UBERON:0002345	96.59	gold quality
right adrenal gland	UBERON:0001233	96.53	gold quality
thyroid gland	UBERON:0002046	96.41	gold quality
left adrenal gland cortex	UBERON:0035825	96.39	gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 20.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	3977.73
E-CURD-126	yes	2892.08
E-MTAB-10553	yes	1498.67
E-HCAD-9	yes	1135.94
E-CURD-46	yes	694.32
E-MTAB-8381	yes	445.48
E-MTAB-9801	yes	414.49
E-HCAD-11	yes	374.66
E-HCAD-1	yes	367.92
E-CURD-112	yes	360.76
E-HCAD-8	yes	269.74
E-GEOD-130473	yes	264.54
E-HCAD-10	yes	208.26
E-HCAD-32	yes	58.10
E-ANND-3	yes	36.09

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

11 targeting CCL14, 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-4283	100.00	66.42	2097
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-4642	97.52	67.60	916

Literature-anchored findings (GeneRIF, showing 17)

• Functional data from activity assays by intracellular calcium flux and inhibition of CCR5-mediated HIV-1 entry show that only CCL14 [9-74] is fully active at these near-physiological concentrations where CCL14 [9-74] is monomeric and CCL14 is dimeric (PMID:17691823)
• CCL14 is involved in mechanisms by which trophoblast cells migrate during early pregnancy. (PMID:18367676)
• SLE, this study reveals strong associations with a marker and a haplotype encompassing the CCL14 gene, which suggests that a lupus relevant variant may lie within or in the proximity of this haplotype. (PMID:18602166)
• the activity of CCL14a might be regulated by stringent proteolytic activation and inactivation steps (PMID:19553544)
• D6 cooperates with CD26 in the negative regulation of CCL14 by the selective degradation of its biologically active isoform. (PMID:19632987)
• enhanced expression in intestinal epithelium in inflammatory bowel disease and display of antibacterial activity (PMID:19812544)
• CCL14 is a critical mediator of the JARID1B/LSD1/NuRD complex in regulation of angiogenesis and metastasis in breast cancer. (PMID:21937684)
• CCL2, 3, 14 have roles in stimulating macrophage bone marrow homing, proliferation, and polarization in multiple myeloma (PMID:26155942)
• TMEM88, CCL14, and CLEC3B genes were stable and available in predicting the survival and palindromia time of hepatocellular carcinoma. These genes could function as potential prognostic genes contributing to improve patients’ outcomes and survival (PMID:28718365)
• CCL14 expression in healthy human palatal mucosa is strongly negatively correlated with serum cotinine levels. (PMID:31682009)
• Serum proteins TGFBI, PCSK9, and CCL14 are potential biomarkers for different traditional Chinese medicine syndromes of multidrug-resistant tuberculosis. (PMID:31909895)
• Lysine demethylase 5B suppresses CC chemokine ligand 14 to promote progression of colorectal cancer through the Wnt/beta-catenin pathway. (PMID:33160990)
• Glycosylation Regulates N-Terminal Proteolysis and Activity of the Chemokine CCL14. (PMID:33988967)
• C-C motif chemokine ligand 14 inhibited colon cancer cell proliferation and invasion through suppressing M2 polarization of tumor-associated macrophages. (PMID:34096611)
• CCL14 exacerbates intraplaque vulnerability by promoting neovascularization in the human carotid plaque. (PMID:35973397)
• Chemokine CCL14 affected the clinical outcome and correlated with immune infiltrates in thyroid carcinoma. (PMID:36409028)
• Performance of urinary C-C motif chemokine ligand 14 for the prediction of persistent acute kidney injury: a systematic review and meta-analysis. (PMID:37596698)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccl35.2	ENSDARG00000070378
danio_rerio	ccl35.1	ENSDARG00000103466

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), CCL23 (ENSG00000274736), CCL16 (ENSG00000275152), CCL4 (ENSG00000275302), CCL18 (ENSG00000275385), CCL15 (ENSG00000275718), CCL4L2 (ENSG00000276070), CCL3L3 (ENSG00000276085), CCL3 (ENSG00000277632)

Protein

Protein identifiers

C-C motif chemokine 14 — Q16627 (reviewed: Q16627)

Alternative names: Chemokine CC-1/CC-3, HCC-1(1-74), NCC-2, Small-inducible cytokine A14

All UniProt accessions (3): A0A087X089, A0A0B4J2G5, Q16627

UniProt curated annotations — full annotation on UniProt →

Function. Has weak activities on human monocytes and acts via receptors that also recognize MIP-1 alpha. It induces intracellular Ca(2+) changes and enzyme release, but no chemotaxis, at concentrations of 100-1,000 nM, and is inactive on T-lymphocytes, neutrophils, and eosinophil leukocytes. Enhances the proliferation of CD34 myeloid progenitor cells. The processed form HCC-1(9-74) is a chemotactic factor that attracts monocytes, eosinophils, and T-cells and is a ligand for CCR1, CCR3 and CCR5.

Subcellular location. Secreted.

Tissue specificity. Expressed constitutively in several normal tissues: spleen, liver, skeletal and heart muscle, gut, and bone marrow, present at high concentrations (1-80 nM) in plasma.

Post-translational modifications. The N-terminal processed forms HCC-1(3-74), HCC-1(4-74) and HCC-1(9-74) are produced in small amounts by proteolytic cleavage after secretion in blood. HCC-1(1-74), but not HCC-1(3-74) and HCC-1(4-74), is partially O-glycosylated; the O-linked glycan consists of one Gal-GalNAc disaccharide, further modified by two N-acetylneuraminic acids.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q16627-1	HCC-1	yes
Q16627-2	HCC-3

RefSeq proteins (2): NP_116738, NP_116739* (*=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 (17 total): strand 5, chain 4, helix 2, disulfide bond 2, signal peptide 1, glycosylation site 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2Q8R	X-RAY DIFFRACTION	1.82
2Q8T	X-RAY DIFFRACTION	2.23

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16627-F1	86.15	0.65

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): 35–59, 36–75

Glycosylation sites (1): 26

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 384 (showing top): GOBP_FOREBRAIN_NEURON_DEVELOPMENT, MODULE_97, ELVIDGE_HYPOXIA_DN, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_LYSOSOMAL_TRANSPORT, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_64, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, MODULE_128, GOBP_VACUOLAR_TRANSPORT

GO Biological Process (10): intracellular calcium ion homeostasis (GO:0006874), inflammatory response (GO:0006954), positive regulation of cell population proliferation (GO:0008284), 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), chemotaxis (GO:0006935), immune response (GO:0006955), signal transduction (GO:0007165)

GO Molecular Function (3): chemokine activity (GO:0008009), CCR chemokine receptor binding (GO:0048020), cytokine activity (GO:0005125)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell migration	2
chemokine receptor binding	2
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
defense response	1
cell population proliferation	1
regulation of cell population proliferation	1
positive 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
response to chemical	1
taxis	1
immune system process	1
response to stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cytokine activity	1
cell chemotaxis	1
receptor ligand activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

694 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCL14	CCR1	P32246	991
CCL14	CCR5	P51681	970
CCL14	CCR2	P41597	763
CCL14	CCR3	P51677	763
CCL14	ACKR1	Q16570	644
CCL14	ACKR2	O00590	612
CCL14	CX3CR1	P49238	584
CCL14	CXCR4	P30991	582
CCL14	CXCR1	P25024	563
CCL14	RARA	P10276	549
CCL14	CXCL10	P02778	549
CCL14	NF1	P21359	549
CCL14	CCL25	O15444	526
CCL14	CCL21	O00585	507
CCL14	CCL27	Q9Y4X3	486

IntAct

10 interactions, top by confidence:

A	B	Type	Score
CCL14	DNLZ	psi-mi:“MI:0914”(association)	0.530
CCL14	CCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CCL14	CCL22	psi-mi:“MI:0407”(direct interaction)	0.440
PIK3R1	CCL14	psi-mi:“MI:0915”(physical association)	0.370
AKT2	CCL14	psi-mi:“MI:0915”(physical association)	0.370
CCL14	PDIA5	psi-mi:“MI:0914”(association)	0.350
ARRB1	CCL14	psi-mi:“MI:0915”(physical association)	0.000
anmK	CCL14	psi-mi:“MI:0915”(physical association)	0.000
ligB	CCL14	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): DNLZ (Affinity Capture-MS), VWA1 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), PDIA5 (Affinity Capture-MS), CCL14 (Affinity Capture-MS), CCL11 (Reconstituted Complex), CCL22 (Reconstituted Complex), CCL14 (Reconstituted Complex), AMZ2 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), DNLZ (Affinity Capture-MS), VWA1 (Affinity Capture-MS), NOA1 (Two-hybrid), EXOSC8 (Two-hybrid)

ESM2 similar proteins: F5HET8, O00626, O88430, O89093, P08317, P10889, P12850, P13500, P14095, P19874, P28291, P30348, P36925, P42830, P42831, P46653, P49873, P51671, P52203, P55774, P61274, P61275, P78556, P80075, P80098, P80221, P82943, Q03366, Q09141, Q16627, Q5RA36, Q62401, Q68AY9, Q68Y88, Q6W5C0, Q8HYP8, Q8HYP9, Q8I021, Q8MIT7, Q8SQB1

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3346 predictions. Top by Δscore:

Variant	Effect	Δscore
12:100282938:TCTA:T	acceptor_loss	1.0000
12:100282939:CTAG:C	acceptor_loss	1.0000
12:100282940:TAGG:T	acceptor_loss	1.0000
12:100282941:A:C	acceptor_loss	1.0000
12:100283144:GCAG:G	donor_gain	1.0000
12:100283145:CAGG:C	donor_loss	1.0000
12:100283148:G:GA	donor_loss	1.0000
12:100283149:T:A	donor_loss	1.0000
12:100291498:TTTA:T	acceptor_loss	1.0000
12:100291500:TA:T	acceptor_loss	1.0000
12:100291501:A:AG	acceptor_gain	1.0000
12:100291501:AG:A	acceptor_gain	1.0000
12:100291502:G:GG	acceptor_gain	1.0000
12:100291502:G:GT	acceptor_loss	1.0000
12:100291502:GG:G	acceptor_gain	1.0000
12:100291502:GGAA:G	acceptor_gain	1.0000
12:100291657:CCAG:C	donor_loss	1.0000
12:100291658:CAGGT:C	donor_loss	1.0000
12:100291659:AGGTA:A	donor_loss	1.0000
12:100291660:GGT:G	donor_loss	1.0000
12:100291661:G:GC	donor_loss	1.0000
12:100291662:T:G	donor_loss	1.0000
12:100296894:C:CG	donor_gain	1.0000
12:100296894:C:G	donor_gain	1.0000
12:100298029:AG:A	acceptor_gain	1.0000
12:100298030:GG:G	acceptor_gain	1.0000
12:100298172:TCAG:T	donor_loss	1.0000
12:100298173:CAGGT:C	donor_loss	1.0000
12:100298175:GGTA:G	donor_loss	1.0000
12:100298176:G:T	donor_loss	1.0000

AlphaMissense

609 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:35983837:C:A	W82C	0.983
17:35983837:C:G	W82C	0.983
17:35983886:A:G	F66S	0.975
17:35984356:C:G	C59S	0.971
17:35984357:A:T	C59S	0.971
17:35983859:C:G	C75S	0.967
17:35983860:A:T	C75S	0.967
17:35984425:C:G	C36S	0.957
17:35984426:A:T	C36S	0.957
17:35983860:A:G	C75R	0.955
17:35984357:A:G	C59R	0.955
17:35983839:A:G	W82R	0.948
17:35983839:A:T	W82R	0.948
17:35983835:A:T	V83D	0.945
17:35983858:A:C	C75W	0.944
17:35984428:C:G	C35S	0.943
17:35984429:A:T	C35S	0.943
17:35983886:A:C	F66C	0.935
17:35983859:C:T	C75Y	0.933
17:35984429:A:G	C35R	0.933
17:35984338:A:T	V65D	0.929
17:35984426:A:G	C36R	0.929
17:35984355:G:C	C59W	0.920
17:35984389:C:G	R48P	0.910
17:35984424:G:C	C36W	0.906
17:35984344:C:T	G63E	0.902
17:35984356:C:T	C59Y	0.900
17:35984425:C:T	C36Y	0.899
17:35983859:C:A	C75F	0.896
17:35983860:A:C	C75G	0.896

dbSNP variants (sampled 300 via entrez): RS1000240361 (17:35987142 G>A), RS1000335053 (17:35984683 C>A,T), RS1000844094 (17:35985722 G>A,C), RS1000942137 (17:35983481 T>A), RS1001279338 (17:35985512 A>C,G), RS1001956231 (17:35984242 C>A,T), RS1002840325 (17:35983298 A>G), RS1003060989 (17:35986431 T>C), RS1003950167 (17:35984423 A>G), RS1004913057 (17:35983531 C>A,T), RS1005516225 (17:35984972 G>C), RS1007063217 (17:35986541 G>T), RS1007692399 (17:35988372 T>A,C), RS1008143462 (17:35985178 C>T), RS1008579928 (17:35982918 C>G,T)

Disease associations

OMIM: gene MIM:601392 | 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
GCST006522_7	Upper eyelid sagging severity	3.000000e-06
GCST006585_1494	Blood protein levels	9.000000e-101
GCST009391_528	Metabolite levels	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010117	pyruvate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects expression, affects methylation	2
GSK-J4	decreases expression	1
ochratoxin A	decreases expression	1
ciglitazone	affects binding, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Lipopolysaccharides	affects cotreatment, affects response to substance, increases expression	1
Valproic Acid	decreases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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