CCL27

Summary

CCL27 (C-C motif chemokine ligand 27, HGNC:10626) is a protein-coding gene on chromosome 9p13.3, encoding C-C motif chemokine 27 (Q9Y4X3). Chemotactic factor that attracts skin-associated memory T-lymphocytes.

This gene is one of several CC cytokine genes clustered on the p-arm of chromosome 9. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The protein encoded by this gene is chemotactic for skin-associated memory T lymphocytes. This cytokine may also play a role in mediating homing of lymphocytes to cutaneous sites. It specifically binds to chemokine receptor 10 (CCR10). Studies of a similar murine protein indicate that these protein-receptor interactions have a pivotal role in T cell-mediated skin inflammation.

Source: NCBI Gene 10850 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 16 total — 1 pathogenic
• MANE Select transcript: NM_006664

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10626
Approved symbol	CCL27
Name	C-C motif chemokine ligand 27
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	ALP, ILC, CTACK, skinkine, ESkine, PESKY, CTAK
Ensembl gene	ENSG00000213927
Ensembl biotype	protein_coding
OMIM	604833
Entrez	10850

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000259631, ENST00000557161

RefSeq mRNA: 1 — MANE Select: NM_006664 NM_006664

CCDS: CCDS6569

Canonical transcript exons

ENST00000259631 — 3 exons

Exon	Start	End
ENSE00000832940	34661890	34662079
ENSE00001331072	34662564	34662657
ENSE00003588508	34662284	34662416

Expression profiles

Bgee: expression breadth ubiquitous, 123 present calls, max score 97.67.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2216 / max 189.9858, expressed in 15 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100538	0.2216	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	97.67	gold quality
zone of skin	UBERON:0000014	97.11	gold quality
skin of leg	UBERON:0001511	96.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.36	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.30	gold quality
cortical plate	UBERON:0005343	64.23	gold quality
stromal cell of endometrium	CL:0002255	64.00	gold quality
ganglionic eminence	UBERON:0004023	61.78	gold quality
primary visual cortex	UBERON:0002436	57.69	gold quality
ventricular zone	UBERON:0003053	57.69	gold quality
lower esophagus mucosa	UBERON:0035834	57.14	gold quality
left testis	UBERON:0004533	54.80	gold quality
testis	UBERON:0000473	54.69	gold quality
skeletal muscle tissue	UBERON:0001134	54.39	gold quality
right testis	UBERON:0004534	54.39	gold quality
cerebellum	UBERON:0002037	54.37	gold quality
cerebellar cortex	UBERON:0002129	54.37	gold quality
cerebellar hemisphere	UBERON:0002245	54.08	gold quality
descending thoracic aorta	UBERON:0002345	53.02	gold quality
substantia nigra	UBERON:0002038	52.89	gold quality
right hemisphere of cerebellum	UBERON:0014890	52.45	gold quality
temporal lobe	UBERON:0001871	51.91	gold quality
amygdala	UBERON:0001876	51.73	gold quality
ectocervix	UBERON:0012249	51.68	gold quality
putamen	UBERON:0001874	51.63	gold quality
hypothalamus	UBERON:0001898	50.93	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	50.42	gold quality
caudate nucleus	UBERON:0001873	50.40	gold quality
muscle tissue	UBERON:0002385	50.40	gold quality
mucosa of stomach	UBERON:0001199	50.12	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	1325.94
E-ANND-3	no	0.16

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3, NFKB1

Literature-anchored findings (GeneRIF, showing 37)

• member of cytokine family; a chemokine (PMID:11821893)
• membrane of cytokine family (PMID:11821900)
• Serum CTACK levels in patients with atopic dermatitis(AD) and psoriasis vulgaris(pSv) were significantly higher. CTACK was strongly expressed in lesional ke-ratinocytes of patients with AD and PsV. (PMID:12642842)
• serum levels significantly correlated with disease activity in patients with atopic dermatitis (PMID:14767451)
• primary Th2-dominated inflammatory reaction in atopic dermatitis induced by TARC leads to an augmented skin-specific inflammatory reaction through CTACK. (PMID:15335355)
• PSGL-1 interacts with CCL27 (CTACK/ILC/ESkine), a skin-associated chemokine that attracts skin-homing T lymphocytes (PMID:15466853)
• CCL27 expression is under the control of NF-kappaB, and that NF-kappaB, as indicated by others, may be an attractive target for therapy in inflammatory skin diseases (PMID:15598438)
• IL-1alpha, TNF-alpha, CCL20, CCL27, and CXCL8 alarm signals are induced in human cells after allergen and irritant exposure (PMID:15679580)
• CCL28 produced by keratinocytes is mediated by different signal pathways from CCL27, and both CCL27 and CCL28 are involved in the pathogenesis of inflammatory skin diseases. (PMID:16433680)
• CCR10-CTACK/CCL27 interactions between circulating T cells and keratinocytes would seem to play an important role in the pathophysiology of mycosis fungoides. (PMID:16675558)
• LTB(4) may enhance TNF-alpha-induced CCL27 production by activating NF-kappaB via the BLT1/G(i/o)/PI3K/ERK pathway in human keratinocytes. (PMID:17581202)
• Human keratinocyte-derived skin tumors may evade T cell-mediated antitumor immune responses by down-regulating the expression of CCL27 through the activation of epidermal growth factor receptor (EGFR)-Ras-MAPK-signaling pathways. (PMID:18025475)
• Serum concentrations of CCL17, CCL22, and CCL27 correlate well with the extent and intensity of Atopic dermatitis (AD) in infants. Of the three Th2 chemokines examined, serum CCL27 correlated most significantly with the severity of AD (PMID:18266834)
• a novel mechanism for the recruitment of CCR10-positive T cells to skin-draining LN following the rapid release of preformed CCL27 from the epidermis (PMID:18453562)
• CCR10+ T cells accumulate preferentially both around and within CCL27+ lymphatic endothelial cells (LEC) podo-low precollector vessels in skin biopsies of human inflammatory disease. (PMID:18772332)
• Significantly lower serum concentration of CXCL-9, CXCL-10, CCL-17, and IL-18 and higher concentration of CXCL-12 and CCL-27 were found in atopic dermatitis patients under 10 years old when compared to Control. (PMID:19639049)
• expression of CCL27 and CCL17 in the inflammatory skin diseases: psoriasis, atopic dermatitis and acute allergic contact dermatitis induced in nickel-sensitive individuals (PMID:21707761)
• IL-1beta-induced CCL27 gene expression in normal human keratinocytes is regulated through the p38 MAPK/MSK1/Mnk1+2 as well as the IKKbeta/NF-kappaB signalling pathways. (PMID:21993219)
• Serum concentrations of TARC and CTACK were significantly higher in AD (atopic dermatitis) children than in healthy controls, and correlated with severity of symptoms. (PMID:22017510)
• low CCL27/CCR10 and CXCL12/CXCR4 intratumoral mRNA ratios are associated with melanoma progression (PMID:22526457)
• CCL27 chemokine implicates cholesteatoma keratinocytes as contributors in cholesteatoma progression. (PMID:23670528)
• Seventeen mediators were identified in burn wound exudates (concentration range 0.0006-9 ng/mg total protein), including the skin-specific chemokine CCL27. (PMID:23980822)
• We show that the adult but not prenatal human keratinocytes produce and release large amounts of CCL27. (PMID:24037339)
• Our study suggests that CTACK/CCL27 may have a pivotal role in the early stage of psoriasis plaque formation, but should be downregulated in the later stage to induce inflammation characteristic for chronic psoriasis plaques (PMID:24710735)
• Findings support the notion that CCR10 and its ligand CCL27 may contribute to the skin infiltration of malignant T-cells in mycosis fungoides and adult T-cell leukemia/lymphoma. (PMID:24970722)
• NOS2 and CCL27: clinical implications for psoriasis and eczema diagnosis and management. (PMID:25539641)
• Our data supports previous reports showing IL-17 and -23 upregulation in association with Multiple sclerosis and potentially identify a previously unknown involvement for CCL27. (PMID:26295034)
• detected in the nucleus in eczema, cytoplasm in psoriasis (PMID:27193975)
• Our study showed that a higher immunostaining of CCL27 in supratumoral epidermis is associated with longer progression-free interval and melanoma-specific survival. (PMID:27325798)
• CCR10/CCL27 crosstalk mediated drug resistance, contributing to failure of proteasome-inhibitors in multiple myeloma. (PMID:27732933)
• We therefore concluded that the cross talk between TNFa and ROS after keratinocytes was exposed to radiation, triggered CCL27 secretion for subsequent inflammation response. (PMID:27879026)
• CCL27 drives baseline recruitment of Herpes simplex virus-specific CD8 T cells expressing CCR10, while interferon-responsive CXCR3 ligands recruit additional cells in response to virus-driven inflammation. (PMID:28701399)
• CTACK is synthesized by oral keratinocytes, and attracts memory T cells and those T cells that express CLA above the level of basal migration (PMID:29171092)
• Plasma CCL27 levels were significantly lower in the VCA-IgA-negative normal subjects than in either the VCA-IgA-positive healthy donorsor the NPC patients. (PMID:29295705)
• The CCL27-CCR10 axis contributes to promoting proliferation, migration, and invasion of lung squamous cell carcinoma. (PMID:36169116)
• Connexin26 Modulates Radiation-Induced Skin Damage by Regulating Chemokine CCL27 through MAPK Signaling. (PMID:37450610)
• Association of CTACK, IL-2, and IL-13 with increased risk of lung cancer: A Mendelian randomization study. (PMID:38885591)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccl27a	ENSDARG00000058570
danio_rerio	ccl27b	ENSDARG00000079713
mus_musculus	Ccl27al	ENSMUSG00000073877
mus_musculus	Ccl27a	ENSMUSG00000073888
mus_musculus	Ccl27b	ENSMUSG00000096826
rattus_norvegicus	Ccl27	ENSRNOG00000039530

Paralogs (1): CCL28 (ENSG00000151882)

Protein

Protein identifiers

C-C motif chemokine 27 — Q9Y4X3 (reviewed: Q9Y4X3)

Alternative names: CC chemokine ILC, Cutaneous T-cell-attracting chemokine, ESkine, IL-11 R-alpha-locus chemokine, Skinkine, Small-inducible cytokine A27

All UniProt accessions (2): Q5VZ77, Q9Y4X3

UniProt curated annotations — full annotation on UniProt →

Function. Chemotactic factor that attracts skin-associated memory T-lymphocytes. May play a role in mediating homing of lymphocytes to cutaneous sites. Binds to CCR10.

Subunit / interactions. Monomer, dimer, and tetramer. Heparin avidly promotes oligomerization. Interacts with TNFAIP6 (via Link domain).

Subcellular location. Secreted.

Tissue specificity. Testis, thymus, placenta, ovary and skin.

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

RefSeq proteins (1): NP_006655* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001811	Chemokine_IL8-like_dom	Domain
IPR036048	Interleukin_8-like_sf	Homologous_superfamily

Pfam: PF00048

UniProt features (16 total): strand 4, helix 3, turn 2, disulfide bond 2, sequence variant 2, signal peptide 1, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2KUM	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y4X3-F1	77.96	0.42

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): 33–62, 34–77

Mutagenesis-validated functional residues (1):

Position	Phenotype
49	9-fold reduction in binding affinity for link domain of tnfaip6.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

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

MSigDB gene sets: 104 (showing top): AP1_01, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, JAEGER_METASTASIS_DN, GCANCTGNY_MYOD_Q6, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, HUMMERICH_MALIGNANT_SKIN_TUMOR_DN, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (9): chemotaxis (GO:0006935), inflammatory response (GO:0006954), immune response (GO:0006955), cell-cell signaling (GO:0007267), neutrophil chemotaxis (GO:0030593), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), cellular response to lipopolysaccharide (GO:0071222), signal transduction (GO:0007165), cell chemotaxis (GO:0060326)

GO Molecular Function (6): chemokine activity (GO:0008009), CCR3 chemokine receptor binding (GO:0031728), CXCR chemokine receptor binding (GO:0045236), cytokine activity (GO:0005125), protein binding (GO:0005515), chemokine receptor binding (GO:0042379)

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

Reactome top-level categories

Rollup of top-6 pathways:

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

Rollup of top GO terms by namespace:

Category	Terms
cell communication	2
signaling	2
chemokine receptor binding	2
response to chemical	1
taxis	1
defense response	1
immune system process	1
response to stimulus	1
granulocyte chemotaxis	1
neutrophil migration	1
antimicrobial humoral response	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
cytokine activity	1
cell chemotaxis	1
CCR chemokine receptor binding	1
receptor ligand activity	1
binding	1
G protein-coupled receptor binding	1
cytokine receptor binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

856 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCL27	CCR10	P46092	999
CCL27	ACKR4	Q9NPB9	998
CCL27	ACKR2	O00590	998
CCL27	CCR7	P32248	946
CCL27	CCL21	O00585	898
CCL27	CCL25	O15444	851
CCL27	CXCL13	O43927	834
CCL27	CCL7	P80098	831
CCL27	IL3	P08700	829
CCL27	CCL17	Q92583	824
CCL27	IL16	Q14005	824
CCL27	CCL24	O00175	812
CCL27	CCR6	P51684	805
CCL27	CCRL2	O00421	804
CCL27	CCL3	P10147	789

IntAct

5 interactions, top by confidence:

A	B	Type	Score
CCL27	CCL5	psi-mi:“MI:0407”(direct interaction)	0.440
CCL5	CCL27	psi-mi:“MI:0407”(direct interaction)	0.440
CCL11	CCL27	psi-mi:“MI:0407”(direct interaction)	0.440
PF4V1	CCL27	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (4): CCL27 (Reconstituted Complex), CCL5 (Reconstituted Complex), CCL27 (Reconstituted Complex), CCL27 (Reconstituted Complex)

ESM2 similar proteins: A8MXK1, O09163, O46633, O54713, O76096, O95684, P01148, P01268, P01269, P01270, P01344, P04089, P07352, P07456, P07490, P10286, P10764, P13562, P14745, P15696, P17647, P23695, P33717, P37042, P41694, P49921, P51459, P51462, P52212, P55247, Q05078, Q08279, Q27IM2, Q28588, Q29423, Q2YDD1, Q3SXP7, Q4R7M4, Q4R7V3, Q5GAN6

Diamond homologs: Q68A91, Q9JIL2, Q9NRJ3, Q9Y4X3, Q9Z1X0

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	1
Likely pathogenic	0
Uncertain significance	14
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
563684	GRCh37/hg19 9p24.3-q13(chr9:203861-67983174)x4	Pathogenic

SpliceAI

275 predictions. Top by Δscore:

Variant	Effect	Δscore
9:34662560:TCAC:T	donor_loss	1.0000
9:34662561:CACC:C	donor_loss	1.0000
9:34662562:A:AC	donor_gain	0.9900
9:34662563:C:CC	donor_gain	0.9900
9:34662563:CCTG:C	donor_gain	0.9900
9:34662562:ACCTG:A	donor_gain	0.9800
9:34662563:CCTGC:C	donor_gain	0.9800
9:34662563:CCT:C	donor_gain	0.9700
9:34662283:CA:C	donor_gain	0.9400
9:34662417:C:CC	acceptor_gain	0.9400
9:34662562:AC:A	donor_gain	0.9400
9:34662563:CC:C	donor_gain	0.9400
9:34662282:A:AC	donor_gain	0.9300
9:34662283:C:CC	donor_gain	0.9300
9:34662415:TG:T	acceptor_gain	0.9200
9:34662462:CCTCT:C	acceptor_gain	0.9200
9:34662463:CTCTC:C	acceptor_gain	0.9200
9:34662464:TCTCT:T	acceptor_gain	0.9200
9:34662077:AGCC:A	acceptor_loss	0.9100
9:34662078:GCC:G	acceptor_loss	0.9100
9:34662080:CTGG:C	acceptor_loss	0.9100
9:34662081:T:A	acceptor_loss	0.9000
9:34662288:AAG:A	donor_gain	0.8700
9:34662080:C:CC	acceptor_gain	0.8600
9:34662317:T:TA	donor_gain	0.8200
9:34662075:GAAGC:G	acceptor_gain	0.7800
9:34662078:GC:G	acceptor_gain	0.7800
9:34662079:CC:C	acceptor_gain	0.7800
9:34662415:TGCTA:T	acceptor_loss	0.7500
9:34662416:GCTAG:G	acceptor_loss	0.7500

AlphaMissense

722 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:34662053:C:G	C77S	0.954
9:34662054:A:T	C77S	0.954
9:34662319:C:A	Q56H	0.947
9:34662319:C:G	Q56H	0.947
9:34662302:C:G	C62S	0.946
9:34662303:A:T	C62S	0.946
9:34662386:C:G	C34S	0.933
9:34662387:A:T	C34S	0.933
9:34662054:A:G	C77R	0.929
9:34662052:G:C	C77W	0.927
9:34662053:C:T	C77Y	0.925
9:34662019:C:A	W88C	0.921
9:34662019:C:G	W88C	0.921
9:34662037:G:C	N82K	0.910
9:34662037:G:T	N82K	0.910
9:34662303:A:G	C62R	0.910
9:34662386:C:T	C34Y	0.905
9:34662387:A:G	C34R	0.902
9:34662077:A:T	L69H	0.899
9:34662301:A:C	C62W	0.899
9:34662385:A:C	C34W	0.897
9:34662302:C:T	C62Y	0.892
9:34662050:A:T	I78N	0.891
9:34662053:C:A	C77F	0.881
9:34662039:T:C	N82D	0.875
9:34662390:A:G	C33R	0.874
9:34662021:A:G	W88R	0.873
9:34662021:A:T	W88R	0.873
9:34662302:C:A	C62F	0.867
9:34662077:A:G	L69P	0.861

dbSNP variants (sampled 300 via entrez): RS1000276988 (9:34664290 C>T), RS1000645702 (9:34661564 G>A,C), RS1004945232 (9:34662725 G>A), RS1005179300 (9:34663174 C>A), RS1005474821 (9:34661668 A>T), RS1008571880 (9:34663864 G>A), RS1008626046 (9:34664231 G>A), RS1009022085 (9:34663651 C>T), RS1009384192 (9:34663903 T>C), RS1009772358 (9:34662196 C>A), RS1012562126 (9:34664326 C>G), RS1013820120 (9:34662930 A>C), RS1014065124 (9:34661626 G>A,C), RS1014844627 (9:34662789 C>T), RS1015226209 (9:34662106 G>A,T)

Disease associations

OMIM: gene MIM:604833 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
terbufos	decreases methylation	1
arsenite	increases methylation	1
nickel sulfate	increases secretion	1
1-carboxyheptylimidazole	decreases reaction, increases expression	1
isoeugenol	increases expression	1
CGP 52608	affects binding, increases reaction	1
emamectin benzoate	increases expression	1
jinfukang	increases expression	1
Terbinafine	increases reaction, decreases reaction, increases expression	1
Carteolol	increases expression	1
Fonofos	decreases methylation	1
Ketoconazole	decreases reaction, increases expression, increases reaction	1
Parathion	decreases methylation	1
Potassium Dichromate	increases secretion	1
Rotenone	decreases expression	1
Sodium Dodecyl Sulfate	increases secretion	1
Valproic Acid	decreases methylation	1
Dinoprostone	increases expression, decreases reaction	1

Clinical trials (associated diseases)

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