CCR7

Summary

CCR7 (C-C motif chemokine receptor 7, HGNC:1608) is a protein-coding gene on chromosome 17q21.2, encoding C-C chemokine receptor type 7 (P32248). Receptor for the MIP-3-beta chemokine.

The protein encoded by this gene is a member of the G protein-coupled receptor family. This receptor was identified as a gene induced by the Epstein-Barr virus (EBV), and is thought to be a mediator of EBV effects on B lymphocytes. This receptor is expressed in various lymphoid tissues and activates B and T lymphocytes. It has been shown to control the migration of memory T cells to inflamed tissues, as well as stimulate dendritic cell maturation. The chemokine (C-C motif) ligand 19 (CCL19/ECL) has been reported to be a specific ligand of this receptor. Signals mediated by this receptor regulate T cell homeostasis in lymph nodes, and may also function in the activation and polarization of T cells, and in chronic inflammation pathogenesis. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 1236 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 39 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_001838

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1608
Approved symbol	CCR7
Name	C-C motif chemokine receptor 7
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	BLR2, CDw197, CD197
Ensembl gene	ENSG00000126353
Ensembl biotype	protein_coding
OMIM	600242
Entrez	1236

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000246657, ENST00000578085, ENST00000579344, ENST00000739600, ENST00000858771

RefSeq mRNA: 5 — MANE Select: NM_001838 NM_001301714, NM_001301716, NM_001301717, NM_001301718, NM_001838

CCDS: CCDS11369, CCDS77026

Canonical transcript exons

ENST00000246657 — 3 exons

Exon	Start	End
ENSE00000863412	40553769	40555818
ENSE00001118361	40565400	40565472
ENSE00003608300	40558893	40558942

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 95.03.

FANTOM5 (CAGE): breadth broad, TPM avg 33.7121 / max 1807.1580, expressed in 393 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165774	32.3373	385
165773	1.3748	180

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vermiform appendix	UBERON:0001154	95.03	gold quality
lymph node	UBERON:0000029	92.66	gold quality
blood	UBERON:0000178	91.93	gold quality
granulocyte	CL:0000094	90.85	gold quality
caecum	UBERON:0001153	90.15	gold quality
thymus	UBERON:0002370	88.74	gold quality
spleen	UBERON:0002106	86.60	gold quality
superficial temporal artery	UBERON:0001614	84.97	gold quality
ileal mucosa	UBERON:0000331	83.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.50	gold quality
bone marrow	UBERON:0002371	79.32	gold quality
tonsil	UBERON:0002372	78.63	gold quality
nasopharynx	UBERON:0001728	78.48	gold quality
epithelium of nasopharynx	UBERON:0001951	78.48	gold quality
bone marrow cell	CL:0002092	77.02	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.74	gold quality
stromal cell of endometrium	CL:0002255	73.84	gold quality
gall bladder	UBERON:0002110	73.72	gold quality
mucosa of transverse colon	UBERON:0004991	73.21	gold quality
rectum	UBERON:0001052	72.88	gold quality
small intestine	UBERON:0002108	71.53	gold quality
right uterine tube	UBERON:0001302	70.97	gold quality
omental fat pad	UBERON:0010414	70.01	gold quality
peritoneum	UBERON:0002358	69.93	gold quality
adipose tissue of abdominal region	UBERON:0007808	68.84	gold quality
amniotic fluid	UBERON:0000173	67.98	silver quality
left uterine tube	UBERON:0001303	67.98	gold quality
endocervix	UBERON:0000458	67.56	gold quality
right lobe of thyroid gland	UBERON:0001119	66.79	gold quality
right lobe of liver	UBERON:0001114	66.18	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	11270.45
E-MTAB-7381	yes	5810.23
E-MTAB-8142	yes	4219.41
E-CURD-89	yes	3388.44
E-CURD-79	yes	1655.03
E-MTAB-6653	yes	1646.53
E-GEOD-70580	yes	1508.74
E-MTAB-8207	yes	979.85
E-CURD-55	yes	544.72
E-CURD-122	yes	89.82
E-CURD-88	yes	52.08
E-HCAD-8	yes	48.03
E-HCAD-1	yes	33.77
E-CURD-46	yes	26.20
E-HCAD-10	yes	22.23

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, BCL6, EPAS1, HIF1A, KLF2, NFKB1, NFKB, NR2C2, PPARG, RELA, RUNX3, SP1, SPI1, TRERF1

miRNA regulators (miRDB)

60 targeting CCR7, 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-4673	100.00	66.64	1490
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-4504	99.10	69.14	1328

Literature-anchored findings (GeneRIF, showing 40)

• Up-regulation OF CCR7 in classical but not in lymphocyte-predominant Hodgkin disease correlates with distinct dissemination of neoplastic cells in lymphoid organs (PMID:11830455)
• important for migration of chronic lymphocytic leukemia cells into lymph nodes (PMID:11929789)
• Few NKT cells express lymphoid tissue-homing chemokine receptors (CCR7 and CXCR5). A population with homing potential for lymph nodes (L selectin(+) CCR7(+)) exists only within a small subset of CD4 NKT cells. (PMID:12070001)
• PGE2 enhanced the expression of the CCL19/CCL21 receptor CCR7 on the cell surface of monocyte-derived dendritic cells (PMID:12149218)
• Data show that interaction between iC3b-opsonized apoptotic cells and immature dendritic cells down-regulated the expression of CD86 and up-regulated expression of CC chemokine receptor 7. (PMID:12486098)
• Coincident expression of CCR6 and CCR7 by pathologic Langerhans cells in Langerhans cell histiocytosis may contribute to their accumulation in nonlymphoid organs such as skin and bone (PMID:12642342)
• Overexpression of CCR7 mRNA in nonsmall cell lung cancer is associated with development of lymph node metastasis (PMID:12673677)
• A striking pattern of early inducible CCR7 expression was seen preferentially on primary T(H)1 cell lines, as compared to T(H)2 cells, and was dependent on the strength and duration of the T cell receptor signal. (PMID:12799021)
• cytomegalovirus infection inhibits dendritic cell migration by impairment of the chemokine receptor switch at the level of the expression of CCR7 molecules (PMID:14990723)
• Premature expression of CCR7 repositions CD4+CD8+ double-positive cells into the thymic medulla of transgenic mice. This repositioning of the thymocytes is accompanied by impairment of their development. (PMID:15034011)
• The expression of VEGF-C and CCR7 is related to lymph node metastasis of gastric carcinoma and both of them may become new targets for the treatment of gastric carcinoma. (PMID:15040017)
• CCR7 induces antiapoptotic signaling in mature DCs (PMID:15059845)
• CCR7 has a role in cell migration induced by CCL21 chemokine in malignant melanoma (PMID:15073111)
• Study of expression of CCR7 and its ligands on dendritic and T cell populations in inflamed central nervous system lesions of multiple sclerosis patients gives insight into pathways for immune cell trafficking and surveillance. (PMID:15122702)
• IL-6 led to inhibition of nuclear factor-kappaB (NF-kappaB) binding activity, regulating CCR7 transcription (PMID:15247147)
• A dose-dependent, mesangioproliferative and antiapoptotic effect of SLC/CCL21 was seen via activation of the chemokine receptor CCR7, constitutively expressed on MC. This suggests involvement in renal inflammation, regeneration and glomerular homeostasis. (PMID:15265234)
• specific CC chemokine receptor 7 residues have roles in receptor activation (PMID:15284247)
• MAPK are necessary for haptens to induce CCR7 expression. (PMID:15304089)
• Activation of CCR7 on mesangial cells by SLC/CCL21 enhances the degree and firmness of cell adhesion and increases cell spreading and the formation of cell-cell contacts (PMID:15569314)
• The CC chemokine receptor 7 consists with the known defect in adhesion and migration of CML cells. (PMID:15674360)
• CCR7 may have a role in the synovial recruitment of memory T cells in juvenile idiopathic arthritis, irrespective of the pattern of lymphoid organisation. (PMID:15743472)
• Epigenetic up-regulation of C-C chemokine receptor 7 expression is associated with melanoma (PMID:15753377)
• CCR7 activates two independent signaling modules, one involving G(i) and a hierarchy of MAPK family members and another involving Rho/Pyk2/cofilin, which control, respectively, chemotaxis and the migratory speed of DCs. (PMID:15778365)
• High expressions of CCR7 is associated with differentiated and intestinal-type gastric cancers (PMID:15867478)
• The selective expression of CCR7 in JDM may open new perspectives in the understanding of the pathogenesis of inflammatory myopathies, offering a new tool for the differential diagnosis of these disorders. (PMID:15950936)
• Results suggest that the chemokine receptor CCR7 is a novel biomarker that can predict lymph node metastases in breast cancer. (PMID:16115904)
• we investigated the expression of CC chemokine receptor 7 (CCR7) in oral and oropharyngeal squamous cell carcinomas (PMID:16223574)
• Data show that CXCL13 and CCL19 together by means of activation of CXCR5 and CCR7 up-regulated PEG10 expression and function in leukemic B cells. (PMID:16225771)
• functional and lineage relationships of three distinct memory CD4 subpopulations distinguished by their expression of the cysteine chemokine receptor CCR7 and the TNFR family member CD27 (PMID:16272303)
• Chemokine receptor 7 is a new player in regulating apoptosis of CD8+ T cells in cancer patients [editorial] (PMID:16278374)
• CCR7 absence on the majority of CD8(+) T cells in the peripheral circulation of patients with squamous cell carcinoma of the head and neck contributes to apoptosis (PMID:16278415)
• CXCR4 and CCR7 are highly expressed in laryngeal carcinoma. Expression was associated with tumor grade, clinical stage and neck lymph node metastasis. (PMID:16494043)
• The maturation, in vitro migration and cytokine production of human DC after stimulation with live H. pylori is reported. (PMID:16500130)
• CD62L and CCR7, as well as dendritic cells, are reduced in non-Hodgkin’s lymphoma (PMID:16690519)
• expression of CCR7 promotes intrahepatic and lymphatic human hepatocellular carcinoma dissemination (PMID:16786131)
• In systemic lupus erythematosus (SLE) patients, significant increases of CCR7-, CD27- and CCR7-, CD27+ and a reduction of CCR7+, CD27+ CD4 memory T cells were found. (PMID:16802356)
• CD45RA+ CCR7- CD8+ T cells are resting memory cells that, upon antigenic stimulation and then proliferate, lose CD45RA, and transiently acquire CCR7. (PMID:16857986)
• The CCL19,CCL21/CCR7 chemokine system is expressed in inflamed muscles of polymyositis and may be involved in the pathomechanism of polymyositis. (PMID:16887149)
• Rapamycin selectively up-regulates CCR7 and enhances the migration of differentiated dendritic cells to regional lymph nodes. (PMID:17006331)
• Significantly higher CCR7 expression is associated with lymph node metastasis in human cervical cancer (PMID:17032700)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccr7	ENSDARG00000044561
mus_musculus	Ccr7	ENSMUSG00000037944
rattus_norvegicus	Ccr7	ENSRNOG00000010665

Paralogs (23): CCR6 (ENSG00000112486), CCRL2 (ENSG00000121797), CCR2 (ENSG00000121807), CXCR4 (ENSG00000121966), ACKR4 (ENSG00000129048), ACKR3 (ENSG00000144476), ACKR2 (ENSG00000144648), RGR (ENSG00000148604), CXCR5 (ENSG00000160683), CCR5 (ENSG00000160791), CXCR1 (ENSG00000163464), CCR1 (ENSG00000163823), CX3CR1 (ENSG00000168329), CXCR6 (ENSG00000172215), XCR1 (ENSG00000173578), CCR9 (ENSG00000173585), CCR8 (ENSG00000179934), CXCR2 (ENSG00000180871), GALR2 (ENSG00000182687), CCR3 (ENSG00000183625), CCR4 (ENSG00000183813), CCR10 (ENSG00000184451), CXCR3 (ENSG00000186810)

Protein

Protein identifiers

C-C chemokine receptor type 7 — P32248 (reviewed: P32248)

Alternative names: BLR2, CDw197, Epstein-Barr virus-induced G-protein coupled receptor 1, MIP-3 beta receptor

All UniProt accessions (4): P32248, A0N0Q0, J3KSS9, J3KTN5

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the MIP-3-beta chemokine. Probable mediator of EBV effects on B-lymphocytes or of normal lymphocyte functions.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in various lymphoid tissues and activated B- and T-lymphocytes, strongly up-regulated in B-cells infected with Epstein-Barr virus and T-cells infected with herpesvirus 6 or 7.

Induction. By Epstein-Barr virus (EBV).

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (5): NP_001288643, NP_001288645, NP_001288646, NP_001288647, NP_001829* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000355	Chemokine_rcpt	Family
IPR001718	Chemokine_CCR7	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (34 total): helix 10, topological domain 8, transmembrane region 7, sequence conflict 2, strand 2, signal peptide 1, chain 1, glycosylation site 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6QZH	X-RAY DIFFRACTION	2.1
9KO2	ELECTRON MICROSCOPY	2.98
9XHH	ELECTRON MICROSCOPY	3
9XHI	ELECTRON MICROSCOPY	3.2
9KO4	ELECTRON MICROSCOPY	3.3
9KO6	ELECTRON MICROSCOPY	3.3
9L16	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32248-F1	78.52	0.33

Antibody-complex structures (SAbDab): 1 — 9KO4

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 (1): 129–210

Glycosylation sites (1): 36

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: 649 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_DENDRITIC_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_DENDRITIC_CELL_MIGRATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_RESPONSE_TO_PROSTAGLANDIN_E

GO Biological Process (53): establishment of T cell polarity (GO:0001768), positive regulation of cell-matrix adhesion (GO:0001954), dendritic cell chemotaxis (GO:0002407), myeloid dendritic cell chemotaxis (GO:0002408), positive regulation of dendritic cell antigen processing and presentation (GO:0002606), positive regulation of hypersensitivity (GO:0002885), positive regulation of humoral immune response (GO:0002922), inflammatory response (GO:0006954), immune response (GO:0006955), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of cytosolic calcium ion concentration (GO:0007204), calcium-mediated signaling (GO:0019722), positive regulation of actin filament polymerization (GO:0030838), positive regulation of pseudopodium assembly (GO:0031274), ruffle organization (GO:0031529), regulation of Cdc42 protein signal transduction (GO:0032489), response to lipopolysaccharide (GO:0032496), regulation of type II interferon production (GO:0032649), regulation of interleukin-1 beta production (GO:0032651), negative regulation of interleukin-12 production (GO:0032695), positive regulation of interleukin-12 production (GO:0032735), positive regulation of Rac protein signal transduction (GO:0035022), CCL19-activated CCR7 signaling pathway (GO:0038119), CCL21-activated CCR7 signaling pathway (GO:0038120), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), negative thymic T cell selection (GO:0045060), positive regulation of cell adhesion (GO:0045785), positive regulation of JNK cascade (GO:0046330), positive regulation of receptor-mediated endocytosis (GO:0048260), homeostasis of number of cells (GO:0048872), positive regulation of T cell receptor signaling pathway (GO:0050862), release of sequestered calcium ion into cytosol (GO:0051209), positive regulation of filopodium assembly (GO:0051491), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), cell chemotaxis (GO:0060326), positive regulation of ERK1 and ERK2 cascade (GO:0070374), cellular response to cytokine stimulus (GO:0071345), cellular response to prostaglandin E stimulus (GO:0071380), response to nitric oxide (GO:0071731), positive regulation of neutrophil chemotaxis (GO:0090023)

GO Molecular Function (7): G protein-coupled receptor activity (GO:0004930), C-C chemokine receptor activity (GO:0016493), chemokine (C-C motif) ligand 19 binding (GO:0035757), chemokine (C-C motif) ligand 21 binding (GO:0035758), C-C motif chemokine 19 receptor activity (GO:0038117), C-C motif chemokine 21 receptor activity (GO:0038121), chemokine receptor activity (GO:0004950)

GO Cellular Component (5): mitochondrion (GO:0005739), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020)

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
C-C chemokine binding	3
C-C chemokine receptor activity	2
cellular anatomical structure	2
establishment of lymphocyte polarity	1
T cell activation	1
regulation of cell-matrix adhesion	1
cell-matrix adhesion	1
positive regulation of cell-substrate adhesion	1
leukocyte chemotaxis	1
dendritic cell migration	1
dendritic cell chemotaxis	1
myeloid leukocyte migration	1
dendritic cell antigen processing and presentation	1
positive regulation of antigen processing and presentation	1
regulation of dendritic cell antigen processing and presentation	1
hypersensitivity	1
positive regulation of acute inflammatory response to antigenic stimulus	1
regulation of hypersensitivity	1
regulation of humoral immune response	1
humoral immune response	1
positive regulation of immune response	1
defense response	1
immune system process	1
response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
regulation of biological quality	1
intracellular signaling cassette	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
pseudopodium assembly	1
regulation of pseudopodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
plasma membrane bounded cell projection organization	1
Cdc42 protein signal transduction	1
regulation of Rho protein signal transduction	1
response to molecule of bacterial origin	1

Protein interactions and networks

STRING

2964 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCR7	CCL21	O00585	999
CCR7	CCL19	Q99731	999
CCR7	CXCL13	O43927	997
CCR7	CXCL12	P48061	997
CCR7	CCL4	P13236	987
CCR7	CCL25	O15444	985
CCR7	CCL20	P78556	984
CCR7	CCL5	P13501	981
CCR7	CCL22	O00626	951
CCR7	CCL27	Q9Y4X3	946
CCR7	CD4	P01730	934
CCR7	CD8A	P01732	928
CCR7	SELL	P14151	913
CCR7	CXCR4	P30991	910
CCR7	CXCL10	P02778	907

IntAct

8 interactions, top by confidence:

A	B	Type	Score
CCR7	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	CCR7	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	CCR7	psi-mi:“MI:0915”(physical association)	0.400
CCR7	CD247	psi-mi:“MI:0915”(physical association)	0.400
CD3E	CCR7	psi-mi:“MI:0915”(physical association)	0.370
CCR7	Arrb2	psi-mi:“MI:2364”(proximity)	0.270
CCR7	CCL21	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (3): CCR7 (Affinity Capture-MS), CCR7 (Affinity Capture-MS), CCL19 (Reconstituted Complex)

ESM2 similar proteins: A4FUQ5, B1PHQ8, B9VR26, O35786, O70129, O88536, O88537, O97571, P0C7U4, P0C7U5, P21109, P21730, P25024, P25025, P25089, P25090, P30992, P30993, P32248, P33766, P35344, P35407, P51686, P55919, P55920, P79175, P79177, P79188, P79189, P79190, P79191, P79234, P79235, P79236, P79237, P79240, P79242, P79243, P97468, P97520

Diamond homologs: A1A5S3, E9QJ73, O08707, P29755, P32248, P33396, P49220, P79785, P97266, Q14330, Q149R9, Q16581, Q28553, Q3T0E9, Q3ZC80, Q4R613, Q58D85, Q5REI5, Q6IYF8, Q6TAC8, Q6Y1R5, Q8K1Z6, Q8NGA4, Q8VIH9, Q920E1, Q924T8, Q95N02, Q96P68, Q99PE3, Q9H1C0, A0T2N3, A4FUQ5, B1PHQ8, B9VR26, O08790, O35210, O35786, O70129, O75388, O77590

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CCL21	up-regulates	CCR7	binding
hsa-let-7a-5p	“down-regulates quantity by repression”	CCR7	“post transcriptional regulation”
CCL19	“up-regulates activity”	CCR7	binding
CCR7	“up-regulates activity”	ARRB2	relocalization
hsa-let-7a-5p	“down-regulates quantity by destabilization”	CCR7	“post transcriptional regulation”

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — DLBCLNOS.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

341 predictions. Top by Δscore:

Variant	Effect	Δscore
17:40555822:C:CT	acceptor_gain	0.9900
17:40555823:G:T	acceptor_gain	0.9800
17:40565397:CAC:C	donor_loss	0.9800
17:40565398:A:AC	donor_gain	0.9800
17:40565398:AC:A	donor_gain	0.9800
17:40565399:C:CC	donor_gain	0.9800
17:40565399:CC:C	donor_gain	0.9800
17:40565394:A:AC	donor_gain	0.9700
17:40565395:C:CC	donor_gain	0.9700
17:40555814:CATAC:C	acceptor_gain	0.9600
17:40555819:C:CC	acceptor_gain	0.9600
17:40557114:T:TA	donor_gain	0.9600
17:40565394:ACTC:A	donor_loss	0.9500
17:40559036:T:A	donor_gain	0.9400
17:40565398:ACC:A	donor_gain	0.9400
17:40565399:CCC:C	donor_gain	0.9400
17:40555816:TAC:T	acceptor_gain	0.9300
17:40555833:A:AC	acceptor_gain	0.9300
17:40558941:CC:C	acceptor_gain	0.9300
17:40558942:CC:C	acceptor_gain	0.9300
17:40555815:ATAC:A	acceptor_gain	0.9200
17:40565399:CCCA:C	donor_gain	0.9200
17:40565399:CCCAG:C	donor_gain	0.9100
17:40555833:A:C	acceptor_gain	0.9000
17:40565395:CTCA:C	donor_gain	0.9000
17:40558887:CCTCA:C	donor_loss	0.8700
17:40558888:CTCA:C	donor_loss	0.8700
17:40558889:TCACC:T	donor_loss	0.8700
17:40558890:CACCT:C	donor_loss	0.8700
17:40558891:A:AC	donor_loss	0.8700

AlphaMissense

2501 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:40554878:C:G	R334P	0.999
17:40554880:G:C	F333L	0.999
17:40554880:G:T	F333L	0.999
17:40554881:A:G	F333S	0.999
17:40554882:A:G	F333L	0.999
17:40555063:G:C	F272L	0.999
17:40555063:G:T	F272L	0.999
17:40555065:A:G	F272L	0.999
17:40555332:A:G	W183R	0.999
17:40555332:A:T	W183R	0.999
17:40555418:C:G	R154P	0.999
17:40555426:G:C	S151R	0.999
17:40555426:G:T	S151R	0.999
17:40555428:T:G	S151R	0.999
17:40555462:G:C	S139R	0.999
17:40555462:G:T	S139R	0.999
17:40555464:T:G	S139R	0.999
17:40555568:T:A	D104V	0.999
17:40555568:T:G	D104A	0.999
17:40555569:C:G	D104H	0.999
17:40555580:A:G	L100P	0.999
17:40555589:A:G	L97P	0.999
17:40555651:A:C	N76K	0.999
17:40555651:A:T	N76K	0.999
17:40555665:C:G	G72R	0.999
17:40554881:A:C	F333C	0.998
17:40554911:G:C	P323R	0.998
17:40554911:G:T	P323H	0.998
17:40555419:G:T	R154S	0.998
17:40555568:T:C	D104G	0.998

dbSNP variants (sampled 300 via entrez): RS1000011225 (17:40554261 C>T), RS1000072817 (17:40562148 C>T), RS1000125082 (17:40562480 C>T), RS1000218234 (17:40561393 T>C), RS1000249262 (17:40561782 C>A,G,T), RS1000499738 (17:40556098 G>A), RS1000550656 (17:40562825 C>T), RS1001630622 (17:40557235 G>A,T), RS1001802222 (17:40563794 C>T), RS1001854625 (17:40564988 G>T), RS1002017865 (17:40557098 C>A,G), RS1002317128 (17:40557974 G>A,C), RS1002581350 (17:40559086 G>C), RS1002675909 (17:40553416 G>C), RS1002688119 (17:40553788 T>A,C,G)

Disease associations

OMIM: gene MIM:600242 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST004627_173	Lymphocyte count	6.000000e-09
GCST005038_121	Allergic disease (asthma, hay fever or eczema)	1.000000e-21
GCST005038_97	Allergic disease (asthma, hay fever or eczema)	2.000000e-26
GCST005536_39	Type 1 diabetes	1.000000e-07
GCST007798_101	Asthma	4.000000e-10
GCST007798_119	Asthma	2.000000e-20
GCST007800_53	Asthma (childhood onset)	2.000000e-18
GCST007800_62	Asthma (childhood onset)	3.000000e-17
GCST009718_15	Eczema	4.000000e-16
GCST009719_2	Allergic rhinitis	3.000000e-17
GCST009798_47	Asthma	3.000000e-10
GCST010984_41	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	8.000000e-15
GCST010985_35	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	7.000000e-14
GCST011742_69	Triglyceride levels in HIV infection	4.000000e-06
GCST011937_4	Takayasu arteritis	7.000000e-06
GCST011939_17	Takayasu arteritis	7.000000e-06
GCST90002388_495	Lymphocyte count	4.000000e-23
GCST90002389_231	Lymphocyte percentage of white cells	7.000000e-19
GCST90002399_240	Neutrophil percentage of white cells	4.000000e-14

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0004847	age at onset
EFO:0004530	triglyceride measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4594 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,078 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL2110727	CENICRIVIROC	3	2,137
CHEMBL216981	NAVARIXIN ANHYDROUS	2	932
CHEMBL6068520	PF-07054894	1	9

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Chemokine receptors

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
CCL19	Agonist	10.0	pKd
CCL21	Agonist	9.3	pIC50
Ccl21b	Agonist	8.33	pIC50

ChEMBL bioactivities

71 potent at pChembl≥5 of 80 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.85	IC50	1.4	nM	CHEMBL41275
8.51	IC50	3.1	nM	CENICRIVIROC
8.19	Ki	6.53	nM	CHEMBL6177821
8.19	Ki	6.457	nM	CHEMBL6177821
8.02	Ki	9.55	nM	CHEMBL6177821
8.01	Ki	9.85	nM	CHEMBL6177821
7.85	Ki	14.2	nM	CHEMBL376414
7.72	Ki	19.05	nM	CHEMBL6174303
7.71	Ki	19.5	nM	CHEMBL6174303
7.48	Ki	33.11	nM	CHEMBL376414
7.46	IC50	35	nM	CHEMBL5433301
7.44	Ki	36.2	nM	CHEMBL376414
7.28	Kd	52.2	nM	CHEMBL6177412
7.16	Kd	69.7	nM	CHEMBL6177412
7.12	Ki	75.86	nM	CHEMBL5433301
7.11	Ki	77.3	nM	CHEMBL5433301
7.10	Ki	79.43	nM	CHEMBL5433301
7.10	Ki	79.43	nM	PF-07054894
7.09	Ki	81.2	nM	PF-07054894
7.00	Ki	98.8	nM	CHEMBL5433301
6.67	Kd	212	nM	CHEMBL6177412
6.46	IC50	350	nM	CHEMBL376414
6.45	IC50	354.8	nM	CHEMBL376414
6.37	IC50	430	nM	CHEMBL5440411
6.37	IC50	430	nM	CHEMBL5434552
6.30	Ki	501.2	nM	CHEMBL6175205
6.30	Ki	504	nM	CHEMBL6175205
5.99	Ki	1023	nM	CHEMBL6176121
5.96	Ki	1090	nM	CHEMBL6176121
5.93	IC50	1180	nM	CHEMBL5427907
5.89	IC50	1288	nM	CHEMBL376414
5.89	IC50	1280	nM	CHEMBL376414
5.83	Ki	1479	nM	CHEMBL384889
5.82	Ki	1520	nM	CHEMBL384889
5.78	IC50	1680	nM	CHEMBL5394402
5.77	Ki	1690	nM	NAVARIXIN ANHYDROUS
5.77	Ki	1698	nM	NAVARIXIN ANHYDROUS
5.75	IC50	1780	nM	CHEMBL5440411
5.64	IC50	2290	nM	CHEMBL5407300
5.61	IC50	2430	nM	CHEMBL5173775
5.60	Ki	2512	nM	CHEMBL6174362
5.59	Ki	2570	nM	CHEMBL6174362
5.54	Ki	2890	nM	CHEMBL216603
5.54	Ki	2884	nM	CHEMBL216603
5.39	Ki	4074	nM	CHEMBL6177696
5.38	Ki	4200	nM	CHEMBL6177696
5.33	IC50	4680	nM	NAVARIXIN ANHYDROUS
5.30	Ki	5012	nM	CHEMBL6175062
5.29	Ki	5190	nM	CHEMBL6177695
5.29	Ki	5100	nM	CHEMBL6175062

PubChem BioAssay actives

20 with measured affinity, of 90 total; 19 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
dimethyl-[[4-[[3-(4-methylphenyl)-8,9-dihydro-7H-benzo[7]annulene-6-carbonyl]amino]phenyl]methyl]-(oxan-4-yl)azanium chloride	1546906: Inhibition of CCR7 (unknown origin)	ic50	0.0014	uM
(5E)-8-[4-(2-butoxyethoxy)phenyl]-1-(2-methylpropyl)-N-[4-[(S)-(3-propylimidazol-4-yl)methylsulfinyl]phenyl]-3,4-dihydro-2H-1-benzazocine-5-carboxamide	1546906: Inhibition of CCR7 (unknown origin)	ic50	0.0031	uM
(2R)-2-[(5-hexylsulfanyl-2H-triazolo[4,5-d]pyrimidin-7-yl)amino]propan-1-ol	1996477: Antagonist activity at CCR7 in human CD4 cells by fluorescence based calcium mobilization assay	ic50	0.4300	uM
(2R)-2-[[5-(cyclohexylmethylsulfanyl)-2H-triazolo[4,5-d]pyrimidin-7-yl]amino]propan-1-ol	1996477: Antagonist activity at CCR7 in human CD4 cells by fluorescence based calcium mobilization assay	ic50	0.4300	uM
(2R)-2-[[5-(2-phenylethylsulfanyl)-2H-triazolo[4,5-d]pyrimidin-7-yl]amino]propan-1-ol	1996477: Antagonist activity at CCR7 in human CD4 cells by fluorescence based calcium mobilization assay	ic50	1.1800	uM
(2R)-2-[[5-(2-cyclohexylethylsulfanyl)-2H-triazolo[4,5-d]pyrimidin-7-yl]amino]propan-1-ol	1996477: Antagonist activity at CCR7 in human CD4 cells by fluorescence based calcium mobilization assay	ic50	1.6800	uM
2-[[5-[(2,3-difluorophenyl)methylsulfanyl]-2H-triazolo[4,5-d]pyrimidin-7-yl]amino]-2-methylpropan-1-ol	1996477: Antagonist activity at CCR7 in human CD4 cells by fluorescence based calcium mobilization assay	ic50	2.2900	uM
(2R)-2-[[5-[(2,3-difluorophenyl)methylsulfanyl]-2H-triazolo[4,5-d]pyrimidin-7-yl]amino]propan-1-ol	1996477: Antagonist activity at CCR7 in human CD4 cells by fluorescence based calcium mobilization assay	ic50	2.4300	uM
2-hydroxy-N,N-dimethyl-3-[[2-[[(1R)-1-(5-methylfuran-2-yl)propyl]amino]-3,4-dioxocyclobuten-1-yl]amino]benzamide	1996477: Antagonist activity at CCR7 in human CD4 cells by fluorescence based calcium mobilization assay	ic50	4.6800	uM
(2R)-2-[[5-(5-methylhexylsulfanyl)-2H-triazolo[4,5-d]pyrimidin-7-yl]amino]propan-1-ol	1996477: Antagonist activity at CCR7 in human CD4 cells by fluorescence based calcium mobilization assay	ic50	5.2800	uM
(2R)-2-[[5-[(2,3-difluorophenyl)methylsulfanyl]-2H-triazolo[4,5-d]pyrimidin-7-yl]amino]butan-1-ol	1996477: Antagonist activity at CCR7 in human CD4 cells by fluorescence based calcium mobilization assay	ic50	5.5600	uM
2-[[5-[(2,3-difluorophenyl)methylsulfanyl]-2H-triazolo[4,5-d]pyrimidin-7-yl]sulfanyl]ethanol	1996477: Antagonist activity at CCR7 in human CD4 cells by fluorescence based calcium mobilization assay	ic50	5.8100	uM
(2R)-2-[[5-(cyclopentylmethylsulfanyl)-2H-triazolo[4,5-d]pyrimidin-7-yl]amino]propan-1-ol	1996477: Antagonist activity at CCR7 in human CD4 cells by fluorescence based calcium mobilization assay	ic50	6.7100	uM
(2S)-2-[[5-[(2,3-difluorophenyl)methylsulfanyl]-2H-triazolo[4,5-d]pyrimidin-7-yl]amino]propan-1-ol	1996477: Antagonist activity at CCR7 in human CD4 cells by fluorescence based calcium mobilization assay	ic50	6.8900	uM
(3R)-3-[[5-[(2,3-difluorophenyl)methylsulfanyl]-2H-triazolo[4,5-d]pyrimidin-7-yl]amino]butan-1-ol	1996477: Antagonist activity at CCR7 in human CD4 cells by fluorescence based calcium mobilization assay	ic50	7.1400	uM
3-[[4-[(1R)-2,2-dimethyl-1-(5-methylfuran-2-yl)propyl]imino-1,1-dioxo-1,2,5-thiadiazol-3-yl]amino]-2-hydroxy-N,N,6-trimethylbenzamide	1996477: Antagonist activity at CCR7 in human CD4 cells by fluorescence based calcium mobilization assay	ic50	7.3000	uM
(2R)-2-[[5-(2-methylpentylsulfanyl)-2H-triazolo[4,5-d]pyrimidin-7-yl]amino]propan-1-ol	1996477: Antagonist activity at CCR7 in human CD4 cells by fluorescence based calcium mobilization assay	ic50	8.4900	uM
2-[[5-[(2,3-difluorophenyl)methylsulfanyl]-2H-triazolo[4,5-d]pyrimidin-7-yl]amino]ethanol	1996477: Antagonist activity at CCR7 in human CD4 cells by fluorescence based calcium mobilization assay	ic50	8.6600	uM
4-[4-[4-[[5-(trifluoromethyl)-2-pyridinyl]amino]cyclohexyl]sulfonylphenyl]pyridine-2-carboxamide	1399333: Inhibition of human CCR7 expressed in CHO cells assessed as decrease in CCL19-induced reduction of forskolin-stimulated cAMP accumulation preincubated for 30 mins followed agonist addition measured after 30 mins by HTRF assay	ic50	9.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
nickel sulfate	affects expression, increases expression	5
Benzo(a)pyrene	increases expression, increases methylation	5
Dinitrochlorobenzene	decreases expression, increases expression, affects reaction	5
Lipopolysaccharides	decreases reaction, increases expression, affects cotreatment, decreases expression, affects expression	3
Tetrachlorodibenzodioxin	affects cotreatment, affects expression, increases expression	3
bisphenol A	affects cotreatment, increases expression	2
sodium arsenite	decreases expression, increases expression	2
Bandrowski’s base	affects expression, increases expression	2
lipopolysaccharide, E. coli O26-B6	increases expression	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Dexamethasone	increases expression, affects cotreatment, decreases reaction	2
Nickel	increases expression	2
Silicon Dioxide	decreases expression	2
Valproic Acid	affects expression, increases expression	2
Dinoprostone	increases expression, affects cotreatment	2
Cyclosporine	increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
TL8-506	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
tributyltin	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
indole-3-carbinol	affects cotreatment, decreases expression	1
mono-(2-ethylhexyl)phthalate	affects cotreatment, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
ammonium hexachloroplatinate	increases expression	1
butyraldehyde	decreases expression	1
ferrous sulfate	decreases expression	1
hydroxycitronellal	increases expression	1
tetrabromobisphenol A	increases expression	1
nickel chloride	increases expression	1

ChEMBL screening assays

46 unique, capped per target: 33 binding, 13 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1070559	Functional	Agonist activity at CCR7 up to 30 uM	The first synthetic agonists of FFA2: Discovery and SAR of phenylacetamides as allosteric modulators. — Bioorg Med Chem Lett
CHEMBL2328029	Binding	Antagonist activity at CCR7 (unknown origin) assessed as inhibition of chemotaxis at 10 uM	1-(4-Phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanones as novel CCR1 antagonists. — Bioorg Med Chem Lett

Cellosaurus cell lines

8 cell lines: 5 cancer cell line, 2 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8CR	Abcam HCT 116 CCR7 KO	Cancer cell line	Male
CVCL_B8TI	Abcam MCF-7 CCR7 KO	Cancer cell line	Female
CVCL_B9EZ	Abcam A-549 CCR7 KO	Cancer cell line	Male
CVCL_KU91	cAMP Hunter CHO-K1 CCR7 Gi	Spontaneously immortalized cell line	Female
CVCL_KW61	PathHunter CHO-K1 CCR7 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KZ39	PathHunter HEK 293 CCR7 beta-arrestin	Transformed cell line	Female
CVCL_KZ98	PathHunter U2OS CCR7 Activated GPCR Internalization	Cancer cell line	Female
CVCL_ZK04	Tango CCR7-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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