CCL22

Summary

CCL22 (C-C motif chemokine ligand 22, HGNC:10621) is a protein-coding gene on chromosome 16q21, encoding C-C motif chemokine 22 (O00626). May play a role in the trafficking of activated/effector T-lymphocytes to inflammatory sites and other aspects of activated T-lymphocyte physiology.

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 monocytes, dendritic cells, natural killer cells and for chronically activated T lymphocytes. It also displays a mild activity for primary activated T lymphocytes and has no chemoattractant activity for neutrophils, eosinophils and resting T lymphocytes. The product of this gene binds to chemokine receptor CCR4. This chemokine may play a role in the trafficking of activated T lymphocytes to inflammatory sites and other aspects of activated T lymphocyte physiology.

Source: NCBI Gene 6367 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 18 total
• Druggable target: yes
• MANE Select transcript: NM_002990

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10621
Approved symbol	CCL22
Name	C-C motif chemokine ligand 22
Location	16q21
Locus type	gene with protein product
Status	Approved
Aliases	MDC, STCP-1, ABCD-1, DC/B-CK, A-152E5.1, MGC34554
Ensembl gene	ENSG00000102962
Ensembl biotype	protein_coding
OMIM	602957
Entrez	6367

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000219235, ENST00000941195

RefSeq mRNA: 1 — MANE Select: NM_002990 NM_002990

CCDS: CCDS10778

Canonical transcript exons

ENST00000219235 — 3 exons

Exon	Start	End
ENSE00000685195	57360437	57360560
ENSE00001301179	57363504	57366189
ENSE00001319882	57358783	57358889

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 86.68.

FANTOM5 (CAGE): breadth broad, TPM avg 112.5079 / max 27635.3358, expressed in 343 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154330	112.5079	343

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	86.68	gold quality
olfactory bulb	UBERON:0002264	85.15	gold quality
vermiform appendix	UBERON:0001154	80.35	gold quality
tongue squamous epithelium	UBERON:0006919	79.59	gold quality
gluteal muscle	UBERON:0002000	79.15	gold quality
heart right ventricle	UBERON:0002080	78.90	gold quality
triceps brachii	UBERON:0001509	78.89	gold quality
caecum	UBERON:0001153	78.79	gold quality
vena cava	UBERON:0004087	78.60	gold quality
diaphragm	UBERON:0001103	78.36	gold quality
cervix squamous epithelium	UBERON:0006922	78.36	gold quality
epithelial cell of pancreas	CL:0000083	78.13	gold quality
mucosa of urinary bladder	UBERON:0001259	77.46	silver quality
myocardium	UBERON:0002349	76.21	gold quality
upper arm skin	UBERON:0004263	75.79	gold quality
cervix epithelium	UBERON:0004801	75.51	gold quality
left ventricle myocardium	UBERON:0006566	75.17	gold quality
lymph node	UBERON:0000029	74.05	gold quality
orbitofrontal cortex	UBERON:0004167	73.63	gold quality
cardiac muscle of right atrium	UBERON:0003379	73.32	gold quality
superficial temporal artery	UBERON:0001614	72.66	gold quality
male germ cell	CL:0000015	71.04	gold quality
periodontal ligament	UBERON:0008266	70.73	gold quality
gingival epithelium	UBERON:0001949	70.43	gold quality
dorsal plus ventral thalamus	UBERON:0001897	70.07	gold quality
body of tongue	UBERON:0011876	70.07	gold quality
subthalamic nucleus	UBERON:0001906	70.02	gold quality
upper leg skin	UBERON:0004262	69.98	silver quality
tongue	UBERON:0001723	69.91	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	69.88	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	28316.36
E-MTAB-8142	yes	20124.92
E-CURD-46	yes	15.18
E-MTAB-9801	yes	6.11
E-MTAB-5061	no	1.89
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, NFKB1, NFKB2, NFKB, RELA, RELB, SPI1

miRNA regulators (miRDB)

145 targeting CCL22, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4271	99.88	68.32	2244

Literature-anchored findings (GeneRIF, showing 40)

• Chronic lymphocytic leukemia B cells are endowed with the capacity to attract CD4+, CD40L+ T cells by producing CCL22, suggesting a vicious circle, leading to the progressive accumulation of the neoplastic cells. (PMID:11981828)
• Neither MDC release nor MDC mRNA was detected in any of the 3 types of fibroblasts stimulated with any of the cytokines examined. (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)
• CCL22 is an antimicrobial protein with bacteriocidal activity against E. coli and S. aureus. (PMID:12949249)
• selectively induced in EBV-infected B cells by LMP-1 protein (PMID:14747532)
• 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)
• Serum levels of TARC and MDC in atopic dermatitis patients were significantly higher than those found in normal controls. (PMID:15113590)
• CCL22 induced accumulation of phosphatidylinositol-(3,4,5)-trisphosphate in the leukemic T cell line CEM. CCL22 also had the ability to chemoattract human Th2 cells and CEM cells in a pertussis toxin-sensitive manner. (PMID:15187160)
• CCL17 and CCL22, which are constitutively produced by immature DCs, mediate both T cell polarization and attraction. (PMID:15210758)
• 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 MDC/CCL22 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)
• MDC/CCL22 has a role in inhibiting progression of lung cancer (PMID:16453150)
• Both a Th1 chemoattractant (CXCL9) and Th2 chemoattractants, CCL17 and CCL22, cooperatively play a role in the development of autoimmune blistering disease. (PMID:16583210)
• CCL22 stimulates phosphatidylinositol-3 kinase-independent phosphorylation of the novel delta isoform of PKC at threonine 505, situated within its activation loop–an event closely associated with increased catalytic activity. (PMID:16614259)
• These data suggest that the CCL22 level produced by monocyte derived dendritic cells thus reflects the disease activity of Atopic dermatitis (AD) and it may also play an important role regarding the production of CCL22 in the pathogenesis of AD. (PMID:17008059)
• 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)
• A trend towards a decreased allelic frequency of the A allele of the CCL22 C/A SNP as well as of the T allele of the CCL17 C/T SNP was found in MS patients compared with controls. (PMID:17967467)
• 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)
• CCL19, CCL20 and CCL22 factors could play an additive role in the pathogenesis of the inflammatory process leading to bronchiolar fibro-obliteration in lung transplant patients (PMID:18047937)
• HTLV-1-infected T cells produce CCL22 through Tax and selectively interact with CCR4+CD4+ T cells, resulting in preferential transmission of HTLV-1 to CCR4+CD4+ T cells. (PMID:18178833)
• MDC/CCL22 is likely to play a role in the development of multiple sclerosis in females only, possibly influencing the intracerebral recruitment of Th2 cells, which produce anti-inflammatory cytokines (PMID:18208895)
• Significantly higher CCL22 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)
• although IE86 does repress the UL144-mediated activation of a synthetic NFkB promoter, it is unable to block UL144-mediated activation of the CCL22 promoter, and this lack of responsiveness to IE86 appears to be regulated by binding of CREB. (PMID:18287226)
• serum CCR4 ligands (CCL17 and CCL22)may be useful inflammatory markers for assessing atopic dermatitis severity in children (PMID:18435706)
• There are elevated concentrations of the chemokines MDC, eotaxin, I-TAC, and MCP-1 in malignant pleural effusions. (PMID:18515987)
• The increased level of CCL17 and CCL22 release was important for acute myelogenous leukemia dendritic cell (AML-DC) chemotaxis of normal T cells. (PMID:18547160)
• Development of allergic disease is associated with a more marked Th2-like deviation already at birth, shown as increased levels of cord blood IgE and MDC (CCL22) and higher ratios of MDC (CCL22) to IP-10 (CXCL10) and I-TAC (CXCL11). (PMID:19175890)
• Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome. (PMID:19244125)
• The adenylyl cyclase-cAMP system has an inhibitory role in IFN-gamma plus TNF-alpha-stimulated production of TARC and MDC in HaCaT keratinocytes by inhibiting NF-kappaB activation through p38 MAPK pathway. (PMID:19371952)
• Endocrine disrupting chemicals suppressed CCL22 and IP-10 levels in cultured monocytes via, at least in part, the MKK1/2-ERK MAPK pathway and histone H4 acetylation. (PMID:19756997)
• Data show that MDC/CCL22 is present in the synovial membrane of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients and in synovial fluid of patients with RA and PsA, which would enable migration of CCR4 expressing memory cells. (PMID:19942450)
• CCL17 and CCL22 within the tumor are related to the increased population of Foxp3(+) T-regs in esophageal squamous cell carcinoma. (PMID:20002703)
• CCL22 may be responsible for the infiltration of CD4(+)CD25(high) T cells into the pleural space of patients with tuberculous pleurisy. (PMID:20337996)
• chemokine CCL22 may have a role in abdominal aortic aneurysm (PMID:20348247)
• Plasma concentration of CCL22 correlates with the frequency of circulating CD4-positive FoxP3-positive (CD4+FoxP3+) regulatory T cells (Tregs) in human T-lymphotropic virus (HTLV) type 1-infected subjects. (PMID:20525891)
• These results indicate that intracellular reactive oxygen species and MAPK kinases both contribute to IFN-gamma-stimulated production of TARC and CCL22 by increasing NF-kappaB activation. (PMID:20625996)
• Contact between monocyte-derived dendritic cells and HCV-JFH1-infected Huh7 cells induced the expression of CCL17 and CCL22. (PMID:21129807)
• Data show that, for the small macrophages in COPD, increased transcript and protein levels for CCL2, CCL7, CCL13 and CCL22 with a more than 100-fold increase for CCL13 mRNA. (PMID:21327296)

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	Ccl22	ENSMUSG00000031779
rattus_norvegicus	Ccl22	ENSRNOG00000016535

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

Protein

Protein identifiers

C-C motif chemokine 22 — O00626 (reviewed: O00626)

Alternative names: CC chemokine STCP-1, MDC(1-69), Macrophage-derived chemokine, Small-inducible cytokine A22, Stimulated T-cell chemotactic protein 1

All UniProt accessions (1): O00626

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in the trafficking of activated/effector T-lymphocytes to inflammatory sites and other aspects of activated T-lymphocyte physiology. Chemotactic for monocytes, dendritic cells and natural killer cells. Mild chemoattractant for primary activated T-lymphocytes and a potent chemoattractant for chronically activated T-lymphocytes but has no chemoattractant activity for neutrophils, eosinophils, and resting T-lymphocytes. Binds to CCR4. Processed forms MDC(3-69), MDC(5-69) and MDC(7-69) seem not be active.

Subcellular location. Secreted.

Tissue specificity. Highly expressed in macrophage and in monocyte-derived dendritic cells, and thymus. Also found in lymph node, appendix, activated monocytes, resting and activated macrophages. Lower expression in lung and spleen. Very weak expression in small intestine. In lymph node expressed in a mature subset of Langerhans’ cells (CD1a+ and CD83+). Expressed in Langerhans’ cell histiocytosis but not in dermatopathic lymphadenopathy. Expressed in atopic dermatitis, allergic contact dermatitis skin, and psoriasis, in both the epidermis and dermis.

Post-translational modifications. The N-terminal processed forms MDC(3-69), MDC(5-69) and MDC(7-69) are produced by proteolytic cleavage after secretion from monocyte derived dendrocytes.

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

RefSeq proteins (1): NP_002981* (*=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 (8 total): chain 4, disulfide bond 2, signal peptide 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00626-F1	88.21	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): 36–60, 37–76

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-6783783	Interleukin-10 signaling
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-5607761	Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-168256	Immune System
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-449147	Signaling by Interleukins
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 267 (showing top): MODULE_92, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELL_CELL_SIGNALING, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_TAXIS, NFKB_C, GOBP_LEUKOCYTE_MIGRATION, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM

GO Biological Process (11): chemotaxis (GO:0006935), inflammatory response (GO:0006954), immune response (GO:0006955), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), response to virus (GO:0009615), positive regulation of cell migration (GO:0030335), eosinophil chemotaxis (GO:0048245), cell chemotaxis (GO:0060326), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), chemokine-mediated signaling pathway (GO:0070098)

GO Molecular Function (4): chemokine activity (GO:0008009), 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-9 pathways:

Category	Pathways
Signaling by Interleukins	2
Peptide ligand-binding receptors	1
CLEC7A (Dectin-1) signaling	1
Immune System	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Cytokine Signaling in Immune system	1
Signaling by GPCR	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
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
response to other organism	1
regulation of cell migration	1
positive regulation of cell motility	1
granulocyte chemotaxis	1
eosinophil migration	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
receptor ligand activity	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1822 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCL22	CCR8	P51685	988
CCL22	CCR3	P51677	986
CCL22	CCR4	P51679	966
CCL22	CCR2	P41597	963
CCL22	ACKR2	O00590	956
CCL22	CCR7	P32248	951
CCL22	ACKR4	Q9NPB9	940
CCL22	CCR5	P51681	924
CCL22	CXCL10	P02778	923
CCL22	CXCR4	P30991	923
CCL22	CCL19	Q99731	907
CCL22	CCR10	P46092	904
CCL22	CX3CL1	P78423	877
CCL22	FOXP3	Q9BZS1	871
CCL22	CXCL5	P42830	869

IntAct

12 interactions, top by confidence:

A	B	Type	Score
CCL22	AQP6	psi-mi:“MI:0915”(physical association)	0.560
CCL22	PLXNA2	psi-mi:“MI:0914”(association)	0.530
CCL14	CCL22	psi-mi:“MI:0407”(direct interaction)	0.440
PF4V1	CCL22	psi-mi:“MI:0407”(direct interaction)	0.440
DPP4	CCL22	psi-mi:“MI:0194”(cleavage reaction)	0.440
CCL22	CRYAB	psi-mi:“MI:0915”(physical association)	0.370
CCL22	GCLC	psi-mi:“MI:0915”(physical association)	0.370
HERC3	CCL22	psi-mi:“MI:0915”(physical association)	0.370
CCL22	HSPA12A	psi-mi:“MI:0914”(association)	0.350

BioGRID (60): KDM4A (Affinity Capture-MS), SEPHS2 (Affinity Capture-MS), PRUNE (Affinity Capture-MS), DPP8 (Affinity Capture-MS), GLS (Affinity Capture-MS), PDIA5 (Affinity Capture-MS), EME1 (Affinity Capture-MS), FAM118B (Affinity Capture-MS), ITPA (Affinity Capture-MS), RAD51D (Affinity Capture-MS), CHD1L (Affinity Capture-MS), ITGA8 (Affinity Capture-MS), PITRM1 (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

217 predictions. Top by Δscore:

Variant	Effect	Δscore
16:57358889:GGTGA:G	donor_loss	1.0000
16:57360435:A:AG	acceptor_gain	1.0000
16:57360436:G:GG	acceptor_gain	1.0000
16:57360556:GTGGT:G	donor_gain	1.0000
16:57358886:GCAG:G	donor_gain	0.9900
16:57360432:CCTA:C	acceptor_loss	0.9900
16:57360435:AGGCC:A	acceptor_loss	0.9900
16:57360436:G:A	acceptor_loss	0.9900
16:57360559:GT:G	donor_gain	0.9900
16:57360561:G:GG	donor_gain	0.9900
16:57360565:G:GG	donor_gain	0.9900
16:57360569:G:GT	donor_gain	0.9900
16:57358890:G:GG	donor_gain	0.9800
16:57360435:AG:A	acceptor_gain	0.9800
16:57360436:GG:G	acceptor_gain	0.9800
16:57360436:GGC:G	acceptor_gain	0.9800
16:57360436:GGCCC:G	acceptor_gain	0.9800
16:57360557:TGGT:T	donor_gain	0.9800
16:57360558:GGTG:G	donor_gain	0.9800
16:57360560:TGTG:T	donor_loss	0.9800
16:57360561:GTGA:G	donor_loss	0.9800
16:57360562:T:TG	donor_loss	0.9800
16:57360563:G:GG	donor_loss	0.9800
16:57360564:A:AT	donor_loss	0.9800
16:57363627:G:GT	donor_gain	0.9800
16:57360564:A:AG	donor_gain	0.9700
16:57360436:GGCC:G	acceptor_gain	0.9600
16:57358885:GGCAG:G	donor_gain	0.9400
16:57358886:GCAGG:G	donor_gain	0.9400
16:57358887:C:T	donor_gain	0.9400

AlphaMissense

596 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:57363555:G:C	W83C	0.996
16:57363555:G:T	W83C	0.996
16:57363506:T:C	L67S	0.991
16:57363532:T:A	C76S	0.986
16:57363533:G:C	C76S	0.986
16:57360541:T:A	C60S	0.984
16:57360542:G:C	C60S	0.984
16:57360472:T:A	C37S	0.981
16:57360473:G:C	C37S	0.981
16:57363533:G:A	C76Y	0.979
16:57360542:G:A	C60Y	0.978
16:57363532:T:C	C76R	0.978
16:57360541:T:C	C60R	0.976
16:57363534:T:G	C76W	0.976
16:57360469:T:A	C36S	0.972
16:57360470:G:C	C36S	0.972
16:57360543:C:G	C60W	0.970
16:57363536:C:A	A77D	0.970
16:57363553:T:A	W83R	0.968
16:57363553:T:C	W83R	0.968
16:57360473:G:A	C37Y	0.966
16:57360472:T:C	C37R	0.965
16:57360554:G:A	G64D	0.964
16:57360474:C:G	C37W	0.959
16:57360542:G:T	C60F	0.957
16:57360520:T:C	F53L	0.953
16:57360522:C:A	F53L	0.953
16:57360522:C:G	F53L	0.953
16:57363535:G:C	A77P	0.953
16:57360469:T:C	C36R	0.952

dbSNP variants (sampled 300 via entrez): RS1000265398 (16:57364793 A>C,T), RS1000431473 (16:57356288 T>C), RS1000702852 (16:57360155 G>A), RS1001094580 (16:57366595 A>T), RS1001701101 (16:57357489 C>T), RS1001984840 (16:57357259 C>A), RS1002445847 (16:57361509 A>T), RS1003144529 (16:57364954 C>T), RS1003254774 (16:57358319 G>A,C), RS1004795336 (16:57365881 G>A), RS1004824716 (16:57366189 G>C), RS1005051417 (16:57360060 C>T), RS1005605882 (16:57362587 G>A,T), RS1005699700 (16:57362815 C>T), RS1006179184 (16:57356874 G>A,C)

Disease associations

OMIM: gene MIM:602957 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005531_83	Multiple sclerosis	2.000000e-06
GCST005752_180	Systemic lupus erythematosus	1.000000e-08
GCST006585_2560	Blood protein levels	7.000000e-34
GCST007400_13	Systemic lupus erythematosus	2.000000e-07
GCST010043_30	Asthma	3.000000e-08
GCST011956_102	Systemic lupus erythematosus	3.000000e-15

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295649 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	decreases expression, decreases reaction, affects cotreatment, increases expression	3
Lipopolysaccharides	increases secretion, increases reaction, increases expression, affects cotreatment, decreases reaction	3
nickel sulfate	affects expression, increases expression	2
Resveratrol	decreases expression, affects cotreatment	2
Vehicle Emissions	affects cotreatment, increases expression, affects reaction, increases reaction	2
Nickel	increases expression	2
Ozone	increases abundance, increases expression, decreases reaction	2
Plant Extracts	affects cotreatment, decreases expression, decreases reaction, increases abundance, increases expression	2
Tretinoin	affects cotreatment, increases expression	2
Valproic Acid	increases expression, decreases expression, affects cotreatment	2
ferric oxide	increases secretion	1
sotorasib	affects cotreatment, decreases expression	1
nifuroxazide	affects cotreatment, decreases reaction, increases expression	1
sodium arsenite	decreases expression	1
nickel chloride	increases secretion	1
perfluorooctanoic acid	increases expression	1
chromic oxide	increases secretion	1
spinasterol	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression, decreases reaction	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
Bandrowski’s base	affects expression	1
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole	increases expression, affects cotreatment, decreases reaction	1
fexofenadine	decreases expression	1
3-(4-methylphenylsulfonyl)-2-propenenitrile	affects cotreatment, decreases reaction, increases expression	1
Dermatophagoides pteronyssinus antigen p 1	affects reaction, increases expression, increases reaction	1
abrine	increases expression	1
2’-hydroxyflavanone	decreases reaction, increases secretion	1
pevonedistat	affects expression	1
manganese ferrite	increases secretion	1
trametinib	affects cotreatment, decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4152014	Binding	Binding affinity to CCL22 (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

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B7WG	Abcam Raji CCL22 KO	Cancer cell line	Male
CVCL_B9X1	Abcam THP-1 CCL22 KO	Cancer cell line	Male
CVCL_D6MH	CNNDi001-A-2	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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