CCL19

Summary

CCL19 (C-C motif chemokine ligand 19, HGNC:10617) is a protein-coding gene on chromosome 9p13.3, encoding C-C motif chemokine 19 (Q99731). May play a role not only in inflammatory and immunological responses but also in normal lymphocyte recirculation and homing.

This antimicrobial gene is one of several CC cytokine genes clustered on the p-arm of chromosome 9. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The cytokine encoded by this gene may play a role in normal lymphocyte recirculation and homing. It also plays an important role in trafficking of T cells in thymus, and in T cell and B cell migration to secondary lymphoid organs. It specifically binds to chemokine receptor CCR7.

Source: NCBI Gene 6363 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 13 total
• MANE Select transcript: NM_006274

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10617
Approved symbol	CCL19
Name	C-C motif chemokine ligand 19
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	ELC, MIP-3b, exodus-3, CKb11
Ensembl gene	ENSG00000172724
Ensembl biotype	protein_coding
OMIM	602227
Entrez	6363

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000311925, ENST00000378800, ENST00000485502

RefSeq mRNA: 1 — MANE Select: NM_006274 NM_006274

CCDS: CCDS6570

Canonical transcript exons

ENST00000311925 — 4 exons

Exon	Start	End
ENSE00001189806	34690210	34690342
ENSE00001189812	34691091	34691276
ENSE00001426976	34689570	34689839
ENSE00001431531	34689930	34690023

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 99.48.

FANTOM5 (CAGE): breadth broad, TPM avg 40.8681 / max 6424.0980, expressed in 237 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100541	40.8071	237
205468	0.0611	26

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	99.48	gold quality
lymph node	UBERON:0000029	98.62	gold quality
caecum	UBERON:0001153	97.43	gold quality
gall bladder	UBERON:0002110	96.98	gold quality
thymus	UBERON:0002370	96.82	gold quality
rectum	UBERON:0001052	94.43	gold quality
mucosa of transverse colon	UBERON:0004991	93.47	gold quality
ileal mucosa	UBERON:0000331	93.27	gold quality
left coronary artery	UBERON:0001626	91.57	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.71	gold quality
coronary artery	UBERON:0001621	90.31	gold quality
epithelium of nasopharynx	UBERON:0001951	90.20	gold quality
nasopharynx	UBERON:0001728	90.19	gold quality
upper leg skin	UBERON:0004262	90.19	gold quality
right coronary artery	UBERON:0001625	88.97	gold quality
tonsil	UBERON:0002372	88.96	gold quality
mucosa of stomach	UBERON:0001199	87.89	gold quality
colonic epithelium	UBERON:0000397	86.60	gold quality
right lobe of thyroid gland	UBERON:0001119	86.07	gold quality
superficial temporal artery	UBERON:0001614	85.79	gold quality
upper arm skin	UBERON:0004263	85.71	gold quality
ascending aorta	UBERON:0001496	85.66	gold quality
thoracic aorta	UBERON:0001515	85.49	gold quality
right lobe of liver	UBERON:0001114	85.10	gold quality
parietal pleura	UBERON:0002400	85.10	gold quality
skin of hip	UBERON:0001554	84.65	gold quality
esophagus mucosa	UBERON:0002469	84.61	gold quality
oral cavity	UBERON:0000167	84.03	gold quality
minor salivary gland	UBERON:0001830	83.39	gold quality
descending thoracic aorta	UBERON:0002345	81.89	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-126	yes	8828.04
E-HCAD-11	yes	8023.01
E-MTAB-9906	yes	2623.80
E-MTAB-8530	yes	2363.72
E-CURD-46	yes	27.46
E-MTAB-8498	yes	8.77
E-ANND-3	no	2.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF1, IRF3, IRF5, IRF7, IRF9, NFKB1, NFKB2, NFKB, RELA, RELB, SP1, STAT1, STAT2

miRNA regulators (miRDB)

14 targeting CCL19, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-548Q	98.71	65.35	563
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-6509-5P	97.39	68.27	969
HSA-MIR-2276-5P	96.27	65.85	937
HSA-MIR-6070	86.37	66.56	59

Literature-anchored findings (GeneRIF, showing 40)

• CC chemokine CCL19 attracts mature T cells out of the fetal thymus organ culture. (PMID:11869682)
• Desensitizing concentrations of CCL21 and CCL19 had no significant effects on T lymphocyte transendothelial migration. (PMID:11870628)
• located in high endothelial venules in an appropriate location to induce transendothelial migration of CLL cells into lymph nodes (PMID:11929789)
• Characterization of mouse CCX-CKR, a receptor for the lymphocyte-attracting chemokines TECK/mCCL25, SLC/mCCL21 and MIP-3beta/mCCL19: comparison to human CCX-CKR. (CCX-CKR) (PMID:11981810)
• CCL19 is an antimicrobial protein with bacteriocidal activity against E. coli. (PMID:12949249)
• migration to CCL19 and CCL21 is dependent on phospholipase C and intracellular calcium flux but not on phosphatidylinositol-3 kinase (PMID:14592837)
• CCL19 and CXCL12 have roles in chemotaxis of mantle cell lymphoma B cells (PMID:14871974)
• MIP-3beta was expressed in the human endometrium, but our results could not strongly support the hypothesis that MIP-3beta is a potential chemoattractant for endometrial NK cells. (PMID:15019823)
• The ccl19 migrated poorly towards the GFP UCB or normal (NL) BM CD34+ cells, p210 UCB and CML CD34+ cells. (PMID:15674360)
• By conditioning naive T cells into a motile dendritic cell-scanning state, CCL19 promotes antigen-independent responses and increases the probability of cognate histocompatibility complex (MHC)-peptide encounter. (PMID:16081805)
• Nitric oxide (NO) donor NOR4 provides a signal allowing LPS-stimulated DCs to migrate toward CCL19. (PMID:16249377)
• The maturation, in vitro migration and cytokine production of human DC after stimulation with live H. pylori is reported. (PMID:16500130)
• The CCL19,CCL21/CCR7 chemokine system is expressed in inflamed muscles of polymyositis and may be involved in the pathomechanism of polymyositis. (PMID:16887149)
• Despite sharing only 25% sequence identity with CCL21, the amino terminal hexapeptide of CCL19 is capable of performing an in vitro role similar to that of CCL21, resulting in G protein activation of the CCR7 receptor. (PMID:16904643)
• CXCL13 and CCL19 cooperatively induce significant resistance to TNF-alpha-mediated apoptosis in acute and chronic B cell leukemia CD23+CD5+ B cells, but not in the cells from cord blood. (PMID:17082584)
• Expression of the CCL19 gene is regulated by a combined action of several members of the NF-kappaB, IRF, and STAT family transcription factors. (PMID:17182562)
• The abundance of CD83+ plasmacytoid dendritic cells (DCs) in perivascular areas and the overexpression of CCL19 and CCL21 in perivascular cellular foci suggest plasmacytoid DCs are central to the muscle inflammation in juvenile dermatomyositis. (PMID:17469160)
• These findings suggest hitherto unknown roles of SMAD transcription factors and of CCL19 in the elicitation phase of allergic contact dermatitis. (PMID:17597826)
• CCL19 plus CXCL13 regulate interaction between B-ALL CD23+CD5+ B cells and CD8+ T cells by inducing activation of PEG10, in turn, resulting in IL-10 overexpression and impairment of tumor-specific cytotoxicity in syngeneic CD8+ T cells. (PMID:17709502)
• This study suggests that CCL19 plays a role in both the physiological immunosurveillance of the healthy CNS and the pathological maintenance of immune cells in the CNS of MS patients. (PMID:17825430)
• after HIV-1 infection of CCL19- or CCL21-treated CD4(+) T-cells, low-level HIV-1 production but high concentrations of integrated HIV-1 DNA, approaching that seen in mitogen-stimulated T-cell blasts, was observed (PMID:17881634)
• 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)
• experiments performed to investigate the survival, adhesion, and metalloproteases secretion indicate that CXCL13 combined with CCL19 and CCL21 mainly affects the chemotaxis of Sezary syndrome cells (PMID:18757429)
• Complement C1q chemoattracts human dendritic cells and enhances migration of mature dendritic cells to CCL19 via activation of AKT and MAPK pathways.( (PMID:18838169)
• macrophages may participate in lymphangiogenesis in diffuse alveolar damage, which is facilitated by CCL19 and CCR7. (PMID:19540558)
• Results demonstrated that RelB/p50 was active only in DC expressing both RelB and p50, and induced CCL19 production, but not DC maturation. (PMID:19655301)
• The CCL19 is known to be critically involved in lymphocyte and dendritic cell trafficking, CCL19-binding competition by CRAM might be involved in modulating these processes. (PMID:20002784)
• Nuclear localization of four and a half LIM domains 2 (FHL2) transgene is lost in mature but not immature bone marrow-derived dendritic cells following stimulation with CCL19. (PMID:20592280)
• Klebsiella pneumoniae-triggered DC recruit human NK cells in a CCR5-dependent manner leading to increased CCL19-responsiveness and activation of NK cells. (PMID:20865789)
• increased expression of MIP-3alpha favors recruitment of immature DCs to the tumour bed, whereas de novo local expression of SLC and MIP-3beta induces accumulation of mature DCs at the tumour margin forming clusters with T-cells (PMID:20969772)
• These results suggest a new combinatorial guiding mechanism by CCL19 and CCL21 for the migration and trafficking of CCR7 expressing leukocytes. (PMID:21464944)
• involvement of CCL19 in AIDS patients with advanced immunodeficiency, potentially mediating both adaptive and maladaptive responses (PMID:22288592)
• a novel signaling pathway that controls EDG-1 up-regulation following stimulation of T cells by CCR7 and CCL19. (PMID:22334704)
• Our findings would suggest that CCL19 and CCL21 may not be associated with cervical lymph node metastasis or other clinical and microscopic factors in oral squamous cell carcinoma. (PMID:22976543)
• CIP4 is expressed at abnormally high levels in CLL cells, where it is required for CCL19-induced chemotaxis. (PMID:23644527)
• Serum CCL19 measurement is a new hallmark of the B cell-mediated rheumatoid arthritis subtype and may predict clinical response to rituximab. (PMID:23740460)
• A high expression of CCL19 was a good prognostic factor of lung adenocarcinoma. (PMID:23922113)
• CCL19 (rather than CCL21) may contribute to the accumulation of dendritic cells and macrophages in the inflamed lungs of patients with eosinophilic pneumonia. (PMID:24111618)
• Serum CCL19 and CCL21 were up-regulated during Rickettsia conorii infection. (PMID:24507453)
• CCL19 promoted monocyte adhesion to HUVEC cells. CCL19 rs2227302 was associated with coronary artery disease in a Chinese Han population. (PMID:24990231)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cxcl32b.1	ENSDARG00000071499
mus_musculus	Ccl19	ENSMUSG00000071005
rattus_norvegicus	Ccl19	ENSRNOG00000015668

Paralogs (26): CX3CL1 (ENSG00000006210), CCL26 (ENSG00000006606), CCL22 (ENSG00000102962), CCL17 (ENSG00000102970), CCL24 (ENSG00000106178), CCL7 (ENSG00000108688), CCL2 (ENSG00000108691), CCL8 (ENSG00000108700), CCL1 (ENSG00000108702), CCL20 (ENSG00000115009), CCL25 (ENSG00000131142), CCL21 (ENSG00000137077), XCL1 (ENSG00000143184), XCL2 (ENSG00000143185), CCL11 (ENSG00000172156), 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 19 — Q99731 (reviewed: Q99731)

Alternative names: Beta-chemokine exodus-3, CK beta-11, Epstein-Barr virus-induced molecule 1 ligand chemokine, Macrophage inflammatory protein 3 beta, Small-inducible cytokine A19

All UniProt accessions (3): Q99731, Q5VZ75, Q6IBD6

UniProt curated annotations — full annotation on UniProt →

Function. May play a role not only in inflammatory and immunological responses but also in normal lymphocyte recirculation and homing. May play an important role in trafficking of T-cells in thymus, and T-cell and B-cell migration to secondary lymphoid organs. Binds to chemokine receptor CCR7. Recombinant CCL19 shows potent chemotactic activity for T-cells and B-cells but not for granulocytes and monocytes. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta-arrestin (ARRB1/2) to ACKR4.

Subunit / interactions. Interacts with TNFAIP6 (via Link domain).

Subcellular location. Secreted.

Tissue specificity. Expressed at high levels in the lymph nodes, thymus and appendix. Intermediate levels seen in colon and trachea, while low levels found in spleen, small intestine, lung, kidney and stomach.

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

RefSeq proteins (1): NP_006265* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000827	Chemokine_CC_CS	Conserved_site
IPR001811	Chemokine_IL8-like_dom	Domain
IPR034133	Chemokine_CC_DCCL	Domain
IPR036048	Interleukin_8-like_sf	Homologous_superfamily
IPR039809	Chemokine_b/g/d	Family

Pfam: PF00048

UniProt features (12 total): strand 5, helix 3, disulfide bond 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7STA	X-RAY DIFFRACTION	2.5
9KO2	ELECTRON MICROSCOPY	2.98
9XHH	ELECTRON MICROSCOPY	3
9KO6	ELECTRON MICROSCOPY	3.3
2MP1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99731-F1	84.08	0.67

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): 29–55, 30–71

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-418594	G alpha (i) signalling events
R-HSA-6783783	Interleukin-10 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-388396	GPCR downstream signalling
R-HSA-449147	Signaling by Interleukins
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 386 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_CELLULAR_RESPONSE_TO_VIRUS, GOBP_DENDRITIC_CELL_DIFFERENTIATION, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_DENDRITIC_CELL_MIGRATION, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_MYELOID_LEUKOCYTE_MIGRATION

GO Biological Process (47): establishment of T cell polarity (GO:0001768), immunological synapse formation (GO:0001771), dendritic cell chemotaxis (GO:0002407), myeloid dendritic cell chemotaxis (GO:0002408), positive regulation of dendritic cell antigen processing and presentation (GO:0002606), intracellular calcium ion homeostasis (GO:0006874), inflammatory response (GO:0006954), immune response (GO:0006955), cell communication (GO:0007154), response to virus (GO:0009615), positive regulation of glycoprotein biosynthetic process (GO:0010560), positive regulation of cell migration (GO:0030335), T cell costimulation (GO:0031295), regulation of Cdc42 protein signal transduction (GO:0032489), positive regulation of interleukin-1 beta production (GO:0032731), positive regulation of interleukin-12 production (GO:0032735), positive regulation of tumor necrosis factor production (GO:0032760), positive regulation of Rac protein signal transduction (GO:0035022), CCL19-activated CCR7 signaling pathway (GO:0038119), positive regulation of T cell proliferation (GO:0042102), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of T-helper 1 cell differentiation (GO:0045627), positive regulation of endocytosis (GO:0045807), positive regulation of JNK cascade (GO:0046330), eosinophil chemotaxis (GO:0048245), positive regulation of receptor-mediated endocytosis (GO:0048260), cell maturation (GO:0048469), positive regulation of chemotaxis (GO:0050921), release of sequestered calcium ion into cytosol (GO:0051209), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), regulation of cell projection assembly (GO:0060491), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), chemokine-mediated signaling pathway (GO:0070098), positive regulation of ERK1 and ERK2 cascade (GO:0070374), cellular response to prostaglandin E stimulus (GO:0071380), response to nitric oxide (GO:0071731), positive regulation of neutrophil chemotaxis (GO:0090023), mature conventional dendritic cell differentiation (GO:0097029), cellular response to virus (GO:0098586), positive regulation of phospholipase C/protein kinase C signal transduction (GO:0141214)

GO Molecular Function (7): chemokine activity (GO:0008009), CCR7 chemokine receptor binding (GO:0031732), CCR10 chemokine receptor binding (GO:0031735), chemokine receptor binding (GO:0042379), 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 GPCR	2
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
Signaling by Interleukins	1
Immune System	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of T cell activation	2
chemokine receptor binding	2
CCR chemokine receptor binding	2
establishment of lymphocyte polarity	1
T cell activation	1
cell-cell recognition	1
lymphocyte activation	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
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
defense response	1
immune system process	1
response to stimulus	1
cellular process	1
response to other organism	1
glycoprotein biosynthetic process	1
positive regulation of macromolecule biosynthetic process	1
regulation of glycoprotein biosynthetic process	1
positive regulation of glycoprotein metabolic process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
lymphocyte costimulation	1
Cdc42 protein signal transduction	1
regulation of Rho protein signal transduction	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
positive regulation of interleukin-1 production	1
positive regulation of cytokine production	1
interleukin-12 production	1
regulation of interleukin-12 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1

Protein interactions and networks

STRING

2120 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCL19	CCR7	P32248	999
CCL19	CXCR5	P32302	997
CCL19	CXCR4	P30991	995
CCL19	CXCL13	O43927	994
CCL19	ACKR4	Q9NPB9	992
CCL19	CCRL2	O00421	990
CCL19	CCR5	P51681	980
CCL19	CCR6	P51684	969
CCL19	ACKR2	O00590	965
CCL19	CXCR3	P49682	964
CCL19	SELL	P14151	932
CCL19	CCL20	P78556	923
CCL19	CCR2	P41597	922
CCL19	CXCL12	P48061	918
CCL19	CX3CR1	P49238	910

IntAct

6 interactions, top by confidence:

A	B	Type	Score
MEOX2	CCL19	psi-mi:“MI:0915”(physical association)	0.560
PF4V1	CCL19	psi-mi:“MI:0407”(direct interaction)	0.440
CCL19	DCTN6	psi-mi:“MI:0914”(association)	0.350
CCL19	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): CCL19 (Reconstituted Complex), CCL19 (Two-hybrid), CCL19 (Reconstituted Complex), CCL19 (Reconstituted Complex), CACNA2D1 (Affinity Capture-MS), KDM4A (Affinity Capture-MS), VWDE (Affinity Capture-MS), TXNDC15 (Affinity Capture-MS), RB1 (Affinity Capture-MS), DCTN6 (Affinity Capture-MS), GPR98 (Affinity Capture-MS), FAT4 (Affinity Capture-MS), SUSD1 (Affinity Capture-MS), MIS18A (Affinity Capture-MS), CCL19 (Affinity Capture-RNA)

ESM2 similar proteins: F5HET8, O00175, O43927, O55038, O62812, O70460, P02776, P02778, P06765, P10146, P10720, P17515, P22362, P27784, P43030, P47992, P47993, P48298, P48973, P49113, P50228, P51670, P80325, P82943, P97545, P97884, P97885, Q03366, Q08782, Q09141, Q102R3, Q62401, Q64H35, Q68FP3, Q68Y86, Q865F5, Q8HYP8, Q8I021, Q8MIZ1, Q95N01

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

2 interactions.

A	Effect	B	Mechanism
CCL19	“up-regulates activity”	ACKR4	binding
CCL19	“up-regulates activity”	CCR7	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

522 predictions. Top by Δscore:

Variant	Effect	Δscore
9:34689840:C:CC	acceptor_gain	1.0000
9:34690209:CA:C	donor_gain	1.0000
9:34690234:T:TA	donor_gain	1.0000
9:34691085:CCTTA:C	donor_loss	1.0000
9:34691086:CTTA:C	donor_loss	1.0000
9:34691087:TTACC:T	donor_loss	1.0000
9:34691088:TA:T	donor_loss	1.0000
9:34691089:A:AG	donor_loss	1.0000
9:34689836:TCAT:T	acceptor_gain	0.9900
9:34689837:CAT:C	acceptor_gain	0.9900
9:34689837:CATC:C	acceptor_gain	0.9900
9:34689838:AT:A	acceptor_gain	0.9900
9:34689838:ATC:A	acceptor_loss	0.9900
9:34689839:TC:T	acceptor_loss	0.9900
9:34689841:T:C	acceptor_loss	0.9900
9:34690208:A:AC	donor_gain	0.9900
9:34690209:C:CC	donor_gain	0.9900
9:34690209:CACTA:C	donor_gain	0.9900
9:34690340:GGG:G	acceptor_gain	0.9900
9:34690341:GG:G	acceptor_gain	0.9900
9:34690343:C:CC	acceptor_gain	0.9900
9:34690348:A:AC	acceptor_gain	0.9900
9:34690348:A:C	acceptor_gain	0.9900
9:34691089:A:AC	donor_gain	0.9900
9:34691090:C:CC	donor_gain	0.9900
9:34689835:TTCAT:T	acceptor_gain	0.9800
9:34690205:CTCA:C	donor_loss	0.9800
9:34690207:CA:C	donor_loss	0.9800
9:34690209:C:CA	donor_loss	0.9800
9:34690209:CACT:C	donor_gain	0.9800

AlphaMissense

626 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:34689972:C:A	W78C	0.999
9:34689972:C:G	W78C	0.999
9:34690021:A:G	F62S	0.998
9:34690021:A:C	F62C	0.997
9:34689994:C:G	C71S	0.993
9:34689995:A:T	C71S	0.993
9:34690279:A:G	I38T	0.993
9:34690228:C:G	C55S	0.992
9:34690229:A:T	C55S	0.992
9:34690254:G:C	F46L	0.990
9:34690254:G:T	F46L	0.990
9:34690256:A:G	F46L	0.990
9:34689974:A:G	W78R	0.989
9:34689974:A:T	W78R	0.989
9:34690303:C:G	C30S	0.988
9:34690304:A:T	C30S	0.988
9:34690229:A:G	C55R	0.987
9:34690279:A:C	I38S	0.987
9:34690279:A:T	I38N	0.987
9:34689995:A:G	C71R	0.986
9:34690216:G:T	A59D	0.986
9:34690306:C:G	C29S	0.986
9:34690307:A:T	C29S	0.986
9:34689991:G:T	A72E	0.982
9:34689994:C:T	C71Y	0.981
9:34690304:A:G	C30R	0.981
9:34689993:A:C	C71W	0.978
9:34690020:G:C	F62L	0.978
9:34690020:G:T	F62L	0.978
9:34690022:A:G	F62L	0.978

dbSNP variants (sampled 300 via entrez): RS1001739187 (9:34692747 G>GCACAATAA), RS1004051980 (9:34692282 T>C), RS1004703267 (9:34689127 C>T), RS1004827028 (9:34690410 C>T), RS1006676047 (9:34690481 G>A), RS1006768715 (9:34693050 C>T), RS1007232060 (9:34692655 G>T), RS1007410787 (9:34692153 C>T), RS1007678977 (9:34691847 CCTCTGGGG>C), RS1008079683 (9:34689257 G>A), RS1008778420 (9:34689851 A>G), RS1008856028 (9:34691399 G>A), RS1009090886 (9:34690798 CCTT>C), RS1009243790 (9:34689489 T>C), RS1009417181 (9:34691496 G>A)

Disease associations

OMIM: gene MIM:602227 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002318_18	Rheumatoid arthritis	3.000000e-15
GCST002318_61	Rheumatoid arthritis	2.000000e-15
GCST006959_148	Rheumatoid arthritis	2.000000e-13
GCST006959_53	Rheumatoid arthritis	1.000000e-13
GCST009391_1412	Metabolite levels	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005132	5-HIAA measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects expression, affects cotreatment, decreases expression	2
Nickel	increases expression	2
Nanotubes, Carbon	increases expression	2
fluorene-9-bisphenol	decreases expression	1
zinc chloride	decreases expression	1
butyraldehyde	decreases expression	1
ferrous sulfate	decreases expression	1
1-nitropyrene	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
2,4-dinitrofluorobenzene sulfonic acid	increases expression	1
lipopolysaccharide, E. coli O26-B6	increases expression	1
diphenylarsinic acid	decreases secretion	1
Aripiprazole	affects cotreatment, increases expression	1
Capecitabine	decreases expression	1
Microplastics	decreases expression, increases abundance	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Aspirin	increases expression	1
Dust	increases expression	1
Eugenol	increases expression	1
Fluorides	affects cotreatment, decreases expression	1
Formaldehyde	increases expression	1
Latex	increases expression	1
Lipopolysaccharides	affects cotreatment, increases expression, affects response to substance	1
Malathion	increases expression	1
Methotrexate	decreases expression	1
Ozone	increases expression, affects cotreatment	1
Perfume	increases expression	1
Polyethylene Terephthalates	decreases expression, increases abundance	1
Silicon Dioxide	decreases expression	1

Clinical trials (associated diseases)

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