CCL17

Summary

CCL17 (C-C motif chemokine ligand 17, HGNC:10615) is a protein-coding gene on chromosome 16q21, encoding C-C motif chemokine 17 (Q92583). Chemokine, which displays chemotactic activity for T lymphocytes, preferentially Th2 cells, but not monocytes or granulocytes.

This antimicrobial gene is one of several Cys-Cys (CC) cytokine genes clustered on the q arm of chromosome 16. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The cytokine encoded by this gene displays chemotactic activity for T lymphocytes, but not monocytes or granulocytes. The product of this gene binds to chemokine receptors CCR4 and CCR8. This chemokine plays important roles in T cell development in thymus as well as in trafficking and activation of mature T cells.

Source: NCBI Gene 6361 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 20 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_002987

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10615
Approved symbol	CCL17
Name	C-C motif chemokine ligand 17
Location	16q21
Locus type	gene with protein product
Status	Approved
Aliases	TARC, ABCD-2
Ensembl gene	ENSG00000102970
Ensembl biotype	protein_coding
OMIM	601520
Entrez	6361

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000219244, ENST00000616880

RefSeq mRNA: 1 — MANE Select: NM_002987 NM_002987

CCDS: CCDS10780

Canonical transcript exons

ENST00000219244 — 4 exons

Exon	Start	End
ENSE00000685201	57415081	57415198
ENSE00001298183	57413874	57414002
ENSE00001518386	57404767	57404836
ENSE00003889146	57415765	57416063

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 83.22.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 9.0162 / max 9016.6813, expressed in 69 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154375	9.0162	69

Top tissues by expression

283 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	83.22	gold quality
vermiform appendix	UBERON:0001154	73.36	gold quality
lymph node	UBERON:0000029	72.84	gold quality
lower esophagus mucosa	UBERON:0035834	72.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	71.22	gold quality
upper lobe of left lung	UBERON:0008952	70.74	gold quality
upper lobe of lung	UBERON:0008948	69.48	gold quality
parotid gland	UBERON:0001831	69.43	gold quality
gall bladder	UBERON:0002110	69.34	gold quality
esophagus mucosa	UBERON:0002469	68.44	gold quality
caecum	UBERON:0001153	68.01	gold quality
type B pancreatic cell	CL:0000169	66.44	gold quality
minor salivary gland	UBERON:0001830	66.39	gold quality
saliva-secreting gland	UBERON:0001044	66.01	gold quality
diaphragm	UBERON:0001103	64.80	gold quality
mouth mucosa	UBERON:0003729	64.78	gold quality
olfactory bulb	UBERON:0002264	64.00	gold quality
triceps brachii	UBERON:0001509	62.82	gold quality
gluteal muscle	UBERON:0002000	62.81	gold quality
vastus lateralis	UBERON:0001379	62.42	gold quality
quadriceps femoris	UBERON:0001377	61.72	gold quality
esophagus squamous epithelium	UBERON:0006920	60.86	silver quality
rectum	UBERON:0001052	60.30	gold quality
lung	UBERON:0002048	60.17	gold quality
tongue squamous epithelium	UBERON:0006919	60.09	gold quality
orbitofrontal cortex	UBERON:0004167	59.82	gold quality
epithelium of esophagus	UBERON:0001976	59.65	gold quality
inferior olivary complex	UBERON:0002127	59.53	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	59.53	gold quality
bronchial epithelial cell	CL:0002328	59.23	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	3494.16
E-ANND-3	no	2.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BCL6, GLI2, RELA, RELB, STAT6

miRNA regulators (miRDB)

5 targeting CCL17, 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-8087	99.90	69.55	1351
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-4433A-3P	97.75	62.82	1435

Literature-anchored findings (GeneRIF, showing 40)

• Evaluation of human thymus and activation-regulated chemokine concentrations in blood using a new sandwich ELISA based on monoclonal antibodies (PMID:12104083)
• TARC may contribute to the pathogenesis of eosinophilic pleural effusions in paragonimiasis. (PMID:12390321)
• TGF-beta(1) might regulate the TARC-related inflammatory processes, which may be important for understanding the pathogenesis of allergic diseases. (PMID:12413771)
• IL-4, but not IL-13, modulates TARC (thymus and activation-regulated chemokine)/CCL17 and IP-10 (interferon-induced protein of 10kDA)/CXCL10 release by TNF-alpha and IFN-gamma in HaCaT cell line. (PMID:12441140)
• TARC was found to be highly expressed in the basal epidermis of the lesional skin of atopic dermatitis patients and only slightly in the non-lesional skin. (PMID:12456591)
• Production of TARC by HaCaT cells is phenomenon specific to cell line, and observation on TARC in HaCaT cells can not be generalized. Normal human epidermal keratinocytes do not produce TARC protein in vitro. (PMID:12615362)
• TGF-beta1 inhibited IFN-gamma and TNF-alpha-induced TARC production in HaCaT cells via Smad2/3. Modulation of TGF-beta/Smad signaling pathway may be beneficial for treatment of atopic dermatitis. (PMID:12615364)
• The combination of TNF-alpha with either IL-4 or IL-13 markedly increased both TARC release and the abundance of TARC mRNA in corneal and dermal fibroblasts, but not in lung fibroblasts. (PMID:12642832)
• important role in the production of antigen specific IgE by T-B cell interaction and in the pathogenesis of atopic dermatitis (PMID:12715916)
• Th2 cytokines enhance TARC expression in human airway smooth muscle cells in IL-4Ralpha genotype-dependent fashion. (PMID:12871855)
• CCL17 is an antimicrobial protein with bacteriocidal activity against E. coli and S. aureus. (PMID:12949249)
• The development of SLE is closely related to the elevation of plasma TARC/CCL17 levels. (PMID:14677179)
• Basal expression and colocalization of CCL17 with E-selectin and ICAM-1 in dermal blood vessels serves to recruit T cells to noninflamed human skin and provides a strong cutaneous immunosurveillance system and model interface with the environment. (PMID:14734737)
• selectively induced in EBV-infected B cells by LMP-1 protein (PMID:14747532)
• serum levels correlate with disease severity specific for atopic dermatitis (PMID:14767451)
• IL-4/IL-13 and IFN-gamma induce alternations in the distribution of adherens junctions in a different fashion and thereby contribute to the reciprocal regulation of TARC/MDC production. (PMID:14962085)
• EBV infection induces TARC expression in B cells; EBNA-LP is one of the viral gene products responsible for the induction. (PMID:15047814)
• Serum levels of TARC and MDC in atopic dermatitis patients were significantly higher than those found in normal controls (PMID:15113590)
• primary Th2-dominated inflammatory reaction in atopic dermatitis induced by TARC leads to an augmented skin-specific inflammatory reaction through CTACK. (PMID:15335355)
• IL-4 and IL-13 secreted from embryo during implantation may up-regulate TARC by endometrial epithelial cells. Production of TARC in endometrium may contribute to modulation of immune reaction by regulation of Th2 lymphocyte trafficking and functions. (PMID:15474066)
• the -431C>T SNP of the TARC gene enhances the promoter activity of TARC gene but is not associated with susceptibility to AD in Japanese population (PMID:15500644)
• findings indicate TARC and MDC are actively involved in pathogenesis of atopic dermatitis and their expression, opposite to that of eotaxin, is strongly associated with clinical picture of atopic dermatitis. (PMID:15813816)
• Elevated bronchial mucosal expression of TARC/CCL17 is implicated in asthma pathogenesis; its action is partly through selective development and retention, or recruitment of T helper type 2, not Th1, receptor-bearing cells. (PMID:15944327)
• CCR4 and TARC/CCL17 play role in pathophysiology of cutaneous lupus erythematosus(CLE). Cytotoxic CD8+ T cells expressing CCR4 appear to be involved in scarring subtypes of CLE. (PMID:15955100)
• Both a Th1 chemoattractant (CXCL9) and Th2 chemoattractants, CCL17 and CCL22, cooperatively play a role in the development of autoimmune blistering disease. (PMID:16583210)
• Thymus and activation-regulated chemokine (TARC)/CCL17 is constitutively expressed in the thymus and is produced by dendritic cells (DC), endothelial cells, keratinocytes (KC) and fibroblasts (review). (PMID:16859899)
• The effects of house dust mite allergen and the cytokines IL-4 and TGF-beta on TARC expression in 16HBE cells and primary bronchial asthma epithelium, was examined. (PMID:17023689)
• Ragweed stimulation significantly increased the production of the Th2-associated cytokines IL-5, IL-9 and IL-13, the chemokines CCL17 and CCL22 and the regulatory cytokine IL-10 in allergic patients (PMID:17517104)
• Bexarotene decreases chemotaxis to CCL17. (PMID:17546636)
• Downregulation of E-cadhedrin expression is associataed with increased EGFR downstream signalling and a subsequent increase in expression of Th2-attracting chemokine TARC. (PMID:17548604)
• Circulating TARC/CCL17 and KL-6 are useful measurements for discriminating acute eosinophilic pneumonia from other causes of acute lung injury. (PMID:17565019)
• In a lung epithelial tumor cell model, respiratory syncytial virus induces the chemokine TARC that has a potential to recruit T helper type 2 (Th2) cells to the lung. (PMID:17641031)
• thymus- and activation-regulated chemokine may have a role in bronchopulmonary aspergillosis in cystic fibrosis patients (PMID:17898016)
• There were no significant differences in CCL17 and CCL22 expression in PBMCs, sera and lesional skins of patients with intrinsic and extrinsic atopic dermatitis. (PMID:17979978)
• Via TARC production, nasal fibroblasts may play an important role in the recruitment of Th2 cells into the sinus mucosa as well as nasal polyps. (PMID:18004070)
• evidence provided that a distal tandem STAT6 element elevates expression from the CCL17 locus approximately twofold. (PMID:18191727)
• Significantly higher CCL17 expression is associated with gastric cancer (PMID:18224687)
• 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)
• Latent membrane protein 1-expressing tumor cells in age-related Epstein-Barr virus-associated B-cell lymphoproliferative disorder were selectively positive for CCL17 and CCL22. (PMID:18271928)
• We investigated whether nasal polyp fibroblasts produce TARC when stimulated with the breakdown products of microorganisms (TLR ligands) and a Th2 cytokine (IL-4). (PMID:18375080)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccl38a.5	ENSDARG00000041835
danio_rerio	ccl38a.4	ENSDARG00000041917
danio_rerio	ccl38.1	ENSDARG00000041919
danio_rerio	ccl38.6	ENSDARG00000041923
mus_musculus	Ccl17	ENSMUSG00000031780
rattus_norvegicus	Ccl17	ENSRNOG00000016278

Paralogs (26): CX3CL1 (ENSG00000006210), CCL26 (ENSG00000006606), CCL22 (ENSG00000102962), 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), CCL14 (ENSG00000276409), CCL3 (ENSG00000277632)

Protein

Protein identifiers

C-C motif chemokine 17 — Q92583 (reviewed: Q92583)

Alternative names: CC chemokine TARC, Small-inducible cytokine A17, Thymus and activation-regulated chemokine

All UniProt accessions (1): Q92583

UniProt curated annotations — full annotation on UniProt →

Function. Chemokine, which displays chemotactic activity for T lymphocytes, preferentially Th2 cells, but not monocytes or granulocytes. Therefore plays an important role in a wide range of inflammatory and immunological processes. Acts by binding to CCR4 at T-cell surface. Mediates GM-CSF/CSF2-driven pain and inflammation. In the brain, required to maintain the typical, highly branched morphology of hippocampal microglia under homeostatic conditions. May be important for the appropriate adaptation of microglial morphology and synaptic plasticity to acute lipopolysaccharide (LPS)-induced neuroinflammation. Plays a role in wound healing, mainly by inducing fibroblast migration into the wound.

Subcellular location. Secreted.

Tissue specificity. Constitutively expressed in thymus. Detected at lower levels in the lung, colon and small intestine. Expressed in stimulated peripheral blood mononuclear cells, but not in resting cells.

Induction. In monocytes, up-regulated by IL4 and by GM-CSF/CSF2 in an IRF4-dependent manner (at protein level).

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

RefSeq proteins (1): NP_002978* (*=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 (14 total): strand 6, helix 2, disulfide bond 2, sequence variant 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7S4N	X-RAY DIFFRACTION	1.65
1NR4	X-RAY DIFFRACTION	1.72
5WK3	X-RAY DIFFRACTION	1.9
7SCV	X-RAY DIFFRACTION	2.01
8FJ2	X-RAY DIFFRACTION	2.07
8SKK	X-RAY DIFFRACTION	2.1
1NR2	X-RAY DIFFRACTION	2.18

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92583-F1	89.69	0.68

Antibody-complex structures (SAbDab): 1 — 5WK3

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): 33–57, 34–73

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-5607761	Dectin-1 mediated noncanonical NF-kB signaling
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-500792	GPCR ligand binding

MSigDB gene sets: 178 (showing top): MODULE_92, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, MODULE_64, GOBP_CELL_CELL_SIGNALING, GOBP_TAXIS, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, MODULE_75, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, MODULE_289, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, RUTELLA_RESPONSE_TO_HGF_VS_CSF2RB_AND_IL4_DN, MODULE_123

GO Biological Process (6): chemotaxis (GO:0006935), inflammatory response (GO:0006954), immune response (GO:0006955), cell-cell signaling (GO:0007267), cell chemotaxis (GO:0060326), signal transduction (GO:0007165)

GO Molecular Function (4): signaling receptor binding (GO:0005102), chemokine activity (GO:0008009), 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-6 pathways:

Category	Pathways
Peptide ligand-binding receptors	1
CLEC7A (Dectin-1) signaling	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Signaling by GPCR	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	2
signaling	2
response to chemical	1
taxis	1
defense response	1
immune system process	1
response to stimulus	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
protein binding	1
cytokine activity	1
chemokine receptor binding	1
cell chemotaxis	1
receptor ligand activity	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1728 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCL17	CCR8	P51685	992
CCL17	ACKR2	O00590	981
CCL17	CCR10	P46092	978
CCL17	ACKR4	Q9NPB9	978
CCL17	CCR3	P51677	960
CCL17	CCL4	P13236	942
CCL17	CCR4	P51679	936
CCL17	CCR5	P51681	925
CCL17	IL13	P35225	903
CCL17	CCRL2	O00421	900
CCL17	CCR6	P51684	900
CCL17	CCL1	P22362	892
CCL17	CXCR3	P49682	878
CCL17	CXCL5	P42830	870
CCL17	CXCL10	P02778	858

IntAct

33 interactions, top by confidence:

A	B	Type	Score
CCL17	CCL5	psi-mi:“MI:0407”(direct interaction)	0.640
CCL5	CCL17	psi-mi:“MI:0407”(direct interaction)	0.640
CCL17	CCL5	psi-mi:“MI:2364”(proximity)	0.640
CCL5	CCL17	psi-mi:“MI:0407”(direct interaction)	0.560
CCL17	CCL5	psi-mi:“MI:0407”(direct interaction)	0.560
CCL21	CCL17	psi-mi:“MI:0407”(direct interaction)	0.560
CCL25	CCL17	psi-mi:“MI:0407”(direct interaction)	0.560
CCL26	CCL17	psi-mi:“MI:0407”(direct interaction)	0.560
CCL28	CCL17	psi-mi:“MI:0407”(direct interaction)	0.560
CCL17	CCL21	psi-mi:“MI:0407”(direct interaction)	0.560
CCL17	CCL26	psi-mi:“MI:0407”(direct interaction)	0.560
CCL17	CCL28	psi-mi:“MI:0407”(direct interaction)	0.560
CCR5	CCL17	psi-mi:“MI:0915”(physical association)	0.500
CCL17	CCR5	psi-mi:“MI:0914”(association)	0.500
CCL17	CCR4	psi-mi:“MI:0914”(association)	0.500
CCR4	CCL17	psi-mi:“MI:0915”(physical association)	0.500
CCL17	PF4	psi-mi:“MI:0407”(direct interaction)	0.440
PF4	CCL17	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL14	CCL17	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (13): CCL21 (Reconstituted Complex), CCL26 (Reconstituted Complex), CCL28 (Reconstituted Complex), CCL5 (Reconstituted Complex), CCL17 (Reconstituted Complex), CCL17 (Reconstituted Complex), CCL17 (Reconstituted Complex), LRP5 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), HLA-DQA1 (Affinity Capture-MS), ADAM17 (Affinity Capture-MS), XIAP (Affinity Capture-MS), CCL17 (Reconstituted Complex)

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

Diamond homologs: F5HET8, O00626, O70460, O88430, O89093, O97919, P10147, P10148, P10855, P13500, P13501, P14097, P16619, P27784, P28291, P30882, P50229, P50230, P50231, P51671, P52203, P55774, P61274, P61275, P80075, P80343, P97272, Q08782, Q16663, Q29288, Q5I1Z0, Q5RA36, Q62401, Q68A92, Q68AY9, Q8HYP4, Q8HYP8, Q8HYP9, Q8HYQ1, Q8HYQ3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 11 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
chemokine-mediated signaling pathway	5	147.3×	4e-09
antimicrobial humoral immune response mediated by antimicrobial peptide	7	103.1×	2e-11
cell chemotaxis	6	101.0×	6e-10
chemotaxis	7	86.5×	3e-11
cell-cell signaling	5	31.6×	4e-06
inflammatory response	8	27.4×	2e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	16
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1807756	GRCh37/hg19 16q11.2-21(chr16:46503573-62203182)x3	Pathogenic

SpliceAI

503 predictions. Top by Δscore:

Variant	Effect	Δscore
16:57415197:GT:G	donor_gain	1.0000
16:57415076:T:A	acceptor_gain	0.9900
16:57415078:CAG:C	acceptor_loss	0.9900
16:57415079:A:AG	acceptor_gain	0.9900
16:57415079:AGC:A	acceptor_loss	0.9900
16:57415080:G:GA	acceptor_gain	0.9900
16:57415080:GC:G	acceptor_gain	0.9900
16:57415080:GCT:G	acceptor_gain	0.9900
16:57415080:GCTC:G	acceptor_gain	0.9900
16:57415188:G:T	donor_gain	0.9900
16:57415194:ATCGT:A	donor_gain	0.9900
16:57415199:G:GG	donor_gain	0.9900
16:57415764:GTTTT:G	acceptor_gain	0.9900
16:57415079:AGCTC:A	acceptor_gain	0.9800
16:57415080:GCTCG:G	acceptor_gain	0.9800
16:57415195:TCGT:T	donor_gain	0.9800
16:57415196:CGT:C	donor_gain	0.9800
16:57415197:GTG:G	donor_gain	0.9800
16:57415197:GTGT:G	donor_loss	0.9800
16:57415198:TG:T	donor_loss	0.9800
16:57415198:TGT:T	donor_gain	0.9800
16:57415199:GTAAG:G	donor_loss	0.9800
16:57415200:T:G	donor_loss	0.9800
16:57415201:A:T	donor_loss	0.9800
16:57415202:A:AC	donor_loss	0.9800
16:57415203:G:C	donor_loss	0.9800
16:57415763:A:AG	acceptor_gain	0.9800
16:57415764:G:GG	acceptor_gain	0.9800
16:57404998:TCACA:T	donor_gain	0.9400
16:57405005:G:GG	donor_gain	0.9300

AlphaMissense

599 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:57415793:T:A	C73S	0.988
16:57415794:G:C	C73S	0.988
16:57415767:T:C	F64S	0.987
16:57415198:T:A	V63D	0.978
16:57415179:T:A	C57S	0.977
16:57415180:G:C	C57S	0.977
16:57415181:C:G	C57W	0.972
16:57415793:T:C	C73R	0.970
16:57415794:G:A	C73Y	0.970
16:57415795:T:G	C73W	0.968
16:57415826:G:C	A84P	0.968
16:57415107:T:A	C33S	0.966
16:57415108:G:C	C33S	0.966
16:57415110:T:A	C34S	0.966
16:57415111:G:C	C34S	0.966
16:57415180:G:A	C57Y	0.965
16:57415839:T:C	L88P	0.963
16:57415179:T:C	C57R	0.962
16:57415150:T:C	L47P	0.960
16:57415793:T:G	C73G	0.959
16:57415767:T:G	F64C	0.957
16:57415191:G:C	A61P	0.952
16:57415122:T:C	F38L	0.950
16:57415124:C:A	F38L	0.950
16:57415124:C:G	F38L	0.950
16:57415107:T:C	C33R	0.948
16:57415110:T:C	C34R	0.946
16:57415791:T:A	I72N	0.945
16:57415192:C:A	A61D	0.944
16:57415123:T:G	F38C	0.942

dbSNP variants (sampled 300 via entrez): RS1000174590 (16:57412720 A>G), RS1000277812 (16:57400065 G>A), RS1000508239 (16:57409955 C>T), RS1000614522 (16:57404466 C>A,T), RS1000668281 (16:57404694 G>A), RS1001007032 (16:57410116 A>G), RS1001182339 (16:57412089 G>A), RS1001291544 (16:57407009 G>A), RS1001340243 (16:57407422 C>A,T), RS1001489939 (16:57400599 G>A), RS1001591274 (16:57395416 G>T), RS1001677534 (16:57412320 G>A), RS1001686056 (16:57395592 C>T), RS1001937998 (16:57400866 G>A), RS1002063919 (16:57416287 C>G,T)

Disease associations

OMIM: gene MIM:601520 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006585_2825	Blood protein levels	6.000000e-30
GCST011913_4	Thymus and reactivation regulated chemokine levels	3.000000e-29

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295915 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Plant Extracts	increases abundance, affects cotreatment, decreases expression, decreases reaction, increases activity (+1 more)	3
3-(4-methylphenylsulfonyl)-2-propenenitrile	affects cotreatment, decreases reaction, increases expression, increases secretion	2
Nickel	increases expression	2
Silicon Dioxide	increases expression, decreases expression	2
Cadmium Chloride	decreases reaction, increases secretion, decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
nifuroxazide	affects cotreatment, decreases reaction, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
zinc chloride	decreases expression	1
ferrous sulfate	decreases expression	1
nickel sulfate	affects expression	1
ceric oxide	affects cotreatment, increases expression	1
spinasterol	decreases expression	1
1-nitropyrene	decreases expression	1
enzacamene	increases expression, increases reaction	1
Bandrowski’s base	affects expression	1
oleanolic acid 3-acetate	increases expression, affects cotreatment, decreases reaction	1
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole	increases expression, affects cotreatment, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
fexofenadine	decreases expression	1
SB 203580	affects cotreatment, decreases reaction, increases expression, increases secretion	1
alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide	increases expression, increases secretion, affects cotreatment, decreases reaction	1
platycodin D	affects cotreatment, decreases reaction, increases expression	1
Houttuynia cordata extract	affects cotreatment, decreases reaction, increases expression, increases secretion	1
abrine	increases expression	1
3-O-beta-D-glucopyranosyl-spinasterol	affects cotreatment, decreases reaction, increases expression, increases secretion	1
pevonedistat	affects expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetylcysteine	decreases reaction, increases secretion	1

ChEMBL screening assays

4 unique, capped per target: 3 admet, 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4152013	Binding	Binding affinity to CCL17 (unknown origin) assessed as inhibition of CXCL12 -induced increase in intracellular calcium level in EGFP-tagged CCR4 expressing HEK cells at 10 uM	Discovery of a Locally and Orally Active CXCL12 Neutraligand (LIT-927) with Anti-inflammatory Effect in a Murine Model of Allergic Airway Hypereosinophilia. — J Med Chem
CHEMBL5375120	ADMET	Inhibition of TARC in human skin immersion culture at 10 uM preincubated for 3 hrs followed by IL-4/IL-13 stimulation measured after 18 hrs by MSD assay relative to control	Design of a Supersoft Topical JAK Inhibitor, Which Is Effective in Human Skin but Rapidly Deactivated in Blood. — J Med Chem

Clinical trials (associated diseases)

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