CXCR5

Summary

CXCR5 (C-X-C motif chemokine receptor 5, HGNC:1060) is a protein-coding gene on chromosome 11q23.3, encoding C-X-C chemokine receptor type 5 (P32302). Cytokine receptor that binds to B-lymphocyte chemoattractant (BLC).

This gene encodes a multi-pass membrane protein that belongs to the CXC chemokine receptor family. It is expressed in mature B-cells and Burkitt’s lymphoma. This cytokine receptor binds to B-lymphocyte chemoattractant (BLC), and is involved in B-cell migration into B-cell follicles of spleen and Peyer patches. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 643 — RefSeq curated summary.

At a glance

• GWAS associations: 35
• Clinical variants (ClinVar): 53 total
• Druggable target: yes
• MANE Select transcript: NM_001716

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1060
Approved symbol	CXCR5
Name	C-X-C motif chemokine receptor 5
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	MDR15, CD185
Ensembl gene	ENSG00000160683
Ensembl biotype	protein_coding
OMIM	601613
Entrez	643

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000292174

RefSeq mRNA: 1 — MANE Select: NM_001716 NM_001716

CCDS: CCDS8402

Canonical transcript exons

ENST00000292174 — 2 exons

Exon	Start	End
ENSE00001053753	118893596	118897787
ENSE00001053754	118883892	118883992

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 88.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.1256 / max 416.2556, expressed in 111 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117054	1.6636	91
117052	0.3268	68
117053	0.1352	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	88.97	gold quality
spleen	UBERON:0002106	85.56	gold quality
lymph node	UBERON:0000029	85.44	gold quality
lower esophagus mucosa	UBERON:0035834	84.12	gold quality
vermiform appendix	UBERON:0001154	78.61	gold quality
cortical plate	UBERON:0005343	78.21	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.96	gold quality
blood	UBERON:0000178	77.56	gold quality
hindlimb stylopod muscle	UBERON:0004252	76.84	gold quality
small intestine Peyer’s patch	UBERON:0003454	76.65	gold quality
apex of heart	UBERON:0002098	76.28	gold quality
ascending aorta	UBERON:0001496	76.02	gold quality
caecum	UBERON:0001153	75.86	gold quality
tibial artery	UBERON:0007610	75.85	gold quality
popliteal artery	UBERON:0002250	75.80	gold quality
thoracic aorta	UBERON:0001515	75.77	gold quality
aorta	UBERON:0000947	75.69	gold quality
ventricular zone	UBERON:0003053	74.93	gold quality
ectocervix	UBERON:0012249	74.87	gold quality
endometrium epithelium	UBERON:0004811	74.62	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	74.51	gold quality
left coronary artery	UBERON:0001626	74.50	gold quality
mucosa of transverse colon	UBERON:0004991	74.44	gold quality
tendon of biceps brachii	UBERON:0008188	74.42	gold quality
stromal cell of endometrium	CL:0002255	74.30	gold quality
right ovary	UBERON:0002118	74.01	gold quality
muscle layer of sigmoid colon	UBERON:0035805	73.97	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	73.87	gold quality
skin of abdomen	UBERON:0001416	73.63	gold quality
lower esophagus	UBERON:0013473	73.56	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	87.32
E-ANND-3	yes	12.37
E-MTAB-8060	no	67.11

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BCL6, NFATC3, NFKB1, POU2F1, PRDM1, RARA, RXRA

miRNA regulators (miRDB)

62 targeting CXCR5, 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-4481	100.00	66.42	1669
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-4784	99.15	67.41	1733

Literature-anchored findings (GeneRIF, showing 40)

• structural requirements for the activation of signal transduction pathways by CXCR5 (PMID:11688722)
• CXCR5 is a common and early marker for newly generated memory CD4+ T cell subsets during ongoing immune responses. (PMID:11714765)
• Most Natural killer t-cells express receptors for extralymphoid tissue or inflammation-related chemokines (CCR2, CCR5, and CXCR3), while few NKT cells express lymphoid tissue-homing chemokine receptors (CCR7 and CXCR5). (PMID:12070001)
• Data show that blr1 was induced early during cell differentiation and because its overexpression accelerated monocytic differentiation, it may be important for signals controlling cell differentiation. (PMID:12324654)
• Data demonstrate a significant age-dependent difference in the response of osteoblasts to CXCR3 and CXCR5 activation. (PMID:14618028)
• CXCR5 and CXCL13 play an essential role in maintaining B- and T-cells in lymphocytic infiltrates and ectopic follicles in thyroid tissue from patients affected by autoimmunity. (PMID:14763921)
• studies suggest that IRBP and S-Ag can initiate innate and, in sensitive individuals, adaptive immune response by attracting iDCs and T and B cells expressing CXCR3 and CXCR5 (PMID:15713799)
• Potenetial role of CXCL13 and its specific receptor CXCR5 in recruitment of B cells in renal allograft rejection. (PMID:15780119)
• 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)
• elevated levels of CXCL13 could cause impaired or altered trafficking of B cells during HIV infection and could contribute to the previously reported loss of CXCR5 (PMID:16318584)
• CCR7 and CXCR5 are differentially expressed on the cell surface of lymphocytes and dendritic cells depending of the stage of cellular differentiation and activation. (review) (PMID:16888899)
• expression of CXCR5 identifies a unique subset of Vgamma9Vdelta2 T cells which express the costimulatory molecules ICOS and CD40L, secrete IL-2, IL-4, and IL-10 and help B cells for Ab production (PMID:17015714)
• Expression of CXCR5 on tumor cells promotes the growth of colon carcinoma cells in the liver. (PMID:17018614)
• CXCR5 plays a role in Chronic lymphocytic leukemia (CLL) cell positioning and cognate interactions between CLL and CXCL13-secreting CD68+ accessory cells in lymphoid tissues. (PMID:17652619)
• CXCR5 is the first chemokine receptor so far identified able to attract in vitro primary metastatic neuroblastoma cells (PMID:17786442)
• Most B cells expressed CXCR5. (PMID:18528326)
• Altered expression of the chemokine receptor-ligand pair, CXCR5/CXCL13, may participate in the establishment of B-cell dysfunctions during HIV-1 infection. (PMID:18780835)
• High levels of CXCR5 is associated with mantle cell lymphoma. (PMID:19228923)
• the CXCL13-CXCR5 axis is significantly associated with prostate cancer progression (PMID:19375853)
• Low-expression frequency for the chemokine receptor CXCR5 is associated with mediastinal large B-cell lymphoma. (PMID:19536742)
• Overexpression of CXCR5 is associated with prostate cancer. (PMID:19610059)
• Results suggest that BLC/CXCL13 as well as its corresponding receptor, CXCR5, may play important roles in the pathogenesis of SLE and in lupus nephritis. (PMID:19955043)
• CXCL13 caused CXCR5-dependent activation of the PI3Kp85alpha in prostate cancer cells (PMID:20412587)
• Sections of the mouse CXCR5 intron significantly align plus/plus with sections of the human intron; the aligned segments are in the same order in mouse as in man and overall cover 13% of the mouse sequence and 17% of the human sequence. (PMID:20809769)
• Central memory CD4 T cells expressing CXCR5 efficiently induced PC differentiation and Ig secretion, and displayed a different profile in terms of cytokine and costimulatory molecule expression. (PMID:21471443)
• these results add new information about the CXCL13-CXCR5 axis in neuroblastic tumors and in the crosstalk between neuroblastic and stromal cells. (PMID:21642390)
• Data indicate that the percentages of CD4(+)CXCR5(+) TFH in IA patients were positively correlated with AST. (PMID:21750724)
• A Bcl-6-CXCR5 axis in T(reg) cells drive the development of follicular regulatory T cells that function to inhibit germinal center reactions. (PMID:21785430)
• The CXCL13-CXCR5 axis is associated with classic determinants of poor prognosis, such as high grade, hormone receptor negativity, and axillary node involvement. (PMID:22607768)
• C-X-C chemokine receptor type 5 gene polymorphisms are associated with non-Hodgkin lymphoma. (PMID:22707196)
• Levels of CXCL13 are increased in carotid atherosclerosis both systemically and within the atherosclerotic lesion. Based on our in vitro findings, we hypothesize a potential plaque stabilizing effects of CXCL13-CXCR5 interaction (PMID:22840692)
• Data indicate that EBI2 expression modulates CXCL13 binding affinity to CXCR5. (PMID:22913878)
• Interruption of CXCL13-CXCR5 axis increases upper genital tract pathology and activation of NKT cells following chlamydial genital infection. (PMID:23189125)
• Polymorphisms in CXCR5 are associated with HIV-associated non-hodgkin B-cell lymphoma. (PMID:23250934)
• A single nucleotide polymorphism in CXCR5, rs630923, is associated with genetic risk for multiple sclerosis. (PMID:23739915)
• specific G protein isoforms coupled to CXCR5 in its resting and active states, were identified. (PMID:23773523)
• Data suggest the involvement of CD4+ CXCR5+ T cells (circulating follicular helper T cells Tfh) in the pathogenesis and progression of chronic lymphocytic leukemia (CLL). (PMID:23807677)
• Results provide additional evidence for a role of host genetic variation in CXCR5 in lymphomagenesis, particularly for FL. (PMID:23812490)
• study discovered multiple susceptibility variants for systemic lupus erythematosus in the 11q23.3 region, including variants in/near PHLDB1 (rs11603023), DDX6 (rs638893) and CXCR5 (rs10892301) (PMID:24001599)
• Human circulating memory T-helper cells expressing PD-1 and CXCR5 are highly functional and correlate with broadly neutralizing HIV antibody responses. (PMID:24035365)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cxcr5	ENSDARG00000010514
mus_musculus	Cxcr5	ENSMUSG00000047880
rattus_norvegicus	Cxcr5	ENSRNOG00000012430

Paralogs (23): CCR6 (ENSG00000112486), CCRL2 (ENSG00000121797), CCR2 (ENSG00000121807), CXCR4 (ENSG00000121966), CCR7 (ENSG00000126353), ACKR4 (ENSG00000129048), ACKR3 (ENSG00000144476), ACKR2 (ENSG00000144648), RGR (ENSG00000148604), 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-X-C chemokine receptor type 5 — P32302 (reviewed: P32302)

Alternative names: Burkitt lymphoma receptor 1, Monocyte-derived receptor 15

All UniProt accessions (2): P32302, A0N0R2

UniProt curated annotations — full annotation on UniProt →

Function. Cytokine receptor that binds to B-lymphocyte chemoattractant (BLC). Involved in B-cell migration into B-cell follicles of spleen and Peyer patches but not into those of mesenteric or peripheral lymph nodes. May have a regulatory function in Burkitt lymphoma (BL) lymphomagenesis and/or B-cell differentiation.

Subcellular location. Cell membrane.

Tissue specificity. Expression in mature B-cells and Burkitt lymphoma cells.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P32302-1	Long	yes
P32302-2	Short

RefSeq proteins (1): NP_001707* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR001053	Chemokine_CXCR5	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (22 total): topological domain 8, transmembrane region 7, glycosylation site 2, sequence variant 2, chain 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32302-F1	80.85	0.50

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): 122–202

Glycosylation sites (2): 28, 196

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 266 (showing top): CREL_01, GOBP_CELL_CHEMOTAXIS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, BASSO_HAIRY_CELL_LEUKEMIA_DN, MODULE_64, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_LYMPH_NODE_DEVELOPMENT, GOCC_CELL_SURFACE, CAGCTG_AP4_Q5, GOBP_LEUKOCYTE_CHEMOTAXIS, NFKB_Q6, GOBP_TAXIS, NFKB_C

GO Biological Process (12): 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), leukocyte chemotaxis (GO:0030595), positive regulation of cytokinesis (GO:0032467), B cell activation (GO:0042113), lymph node development (GO:0048535), cell chemotaxis (GO:0060326), chemotaxis (GO:0006935), signal transduction (GO:0007165), chemokine-mediated signaling pathway (GO:0070098)

GO Molecular Function (5): G protein-coupled receptor activity (GO:0004930), C-C chemokine receptor activity (GO:0016493), C-X-C chemokine receptor activity (GO:0016494), C-C chemokine binding (GO:0019957), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Peptide ligand-binding receptors	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	2
chemokine receptor activity	2
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
leukocyte migration	1
cell chemotaxis	1
cytokinesis	1
regulation of cytokinesis	1
positive regulation of cell division	1
positive regulation of cell cycle process	1
lymphocyte activation	1
hematopoietic or lymphoid organ development	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
response to chemical	1
taxis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cytokine-mediated signaling pathway	1
cellular response to chemokine	1
transmembrane signaling receptor activity	1
C-C chemokine binding	1
C-X-C chemokine binding	1
chemokine binding	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1948 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CXCR5	CXCL13	O43927	999
CXCR5	CXCL12	P48061	997
CXCR5	CCL19	Q99731	997
CXCR5	CCL21	O00585	993
CXCR5	ICOS	Q9Y6W8	941
CXCR5	CXCL10	P02778	920
CXCR5	CD4	P01730	904
CXCR5	BCL6	P41182	894
CXCR5	CXCL9	Q07325	891
CXCR5	CCR7	P32248	882
CXCR5	CCL5	P13501	857
CXCR5	CXCR4	P30991	855
CXCR5	CD38	P28907	853
CXCR5	CD8A	P01732	851
CXCR5	ITIH4	Q14624	843

IntAct

35 interactions, top by confidence:

A	B	Type	Score
CXCR5	GNAI2	psi-mi:“MI:2364”(proximity)	0.720
CXCR5	GNAI2	psi-mi:“MI:0915”(physical association)	0.720
GNAI2	CXCR5	psi-mi:“MI:0217”(phosphorylation reaction)	0.720
GNAI2	CXCR5	psi-mi:“MI:0915”(physical association)	0.720
CXCR5	RAMP2	psi-mi:“MI:0915”(physical association)	0.470
RAMP2	CXCR5	psi-mi:“MI:0915”(physical association)	0.470
CXCR5	RAMP2	psi-mi:“MI:2364”(proximity)	0.470
CXCR5	GHDC	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	CXCR5	psi-mi:“MI:0915”(physical association)	0.400
CXCR5	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
GNAQ	CXCR5	psi-mi:“MI:0915”(physical association)	0.400
CXCR5	GNAO1	psi-mi:“MI:0915”(physical association)	0.400
CXCR4	CXCR5	psi-mi:“MI:0915”(physical association)	0.400
CXCR5	CXCR4	psi-mi:“MI:0915”(physical association)	0.400
GNA13	CXCR5	psi-mi:“MI:0915”(physical association)	0.400
CXCR5	GNA13	psi-mi:“MI:0915”(physical association)	0.400
GNB3	CXCR5	psi-mi:“MI:0915”(physical association)	0.400
CXCR5	GNB3	psi-mi:“MI:0915”(physical association)	0.400
CXCR5	GNG8	psi-mi:“MI:0915”(physical association)	0.400
GNA13	F2R	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (10): CXCR4 (Affinity Capture-Western), GNB3 (Affinity Capture-Western), GNG8 (Affinity Capture-Western), GNAI2 (Affinity Capture-Western), GNA11 (Affinity Capture-Western), GNA13 (Affinity Capture-Western), CXCR5 (Affinity Capture-Western), CXCR5 (Affinity Capture-Western), CXCR5 (Affinity Capture-Western), GNAI2 (Co-localization)

ESM2 similar proteins: A0A0R4IM31, A0A0R4IP11, E9QJ73, F8VQN3, O00270, O00421, O15218, O35457, O97663, P31392, P32302, P34997, P43142, P49685, Q04683, Q0II78, Q0VDU3, Q149R9, Q16570, Q3ZC80, Q67ES2, Q6XKD3, Q75ZH0, Q7TMA4, Q7TQA9, Q7TQP4, Q7TSN5, Q7TSN6, Q863H8, Q8BZR0, Q8TDV2, Q95LF2, Q95LF3, Q95LF4, Q95LF5, Q95LF7, Q95LF9, Q95LG5, Q96CH1, Q96G91

Diamond homologs: A0A287A2K5, C8YUV0, O00155, O02836, O08786, O15973, O18935, O19012, O19014, O19025, O19032, O19054, O19091, O62729, O77408, O77700, O77721, O77830, O97665, O97772, P04761, P08482, P0C5I1, P11229, P12657, P17200, P18089, P19328, P22270, P25021, P30545, P30551, P30552, P30553, P30796, P32211, P32238, P32239, P32302, P46627

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 12 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Thrombin signalling through proteinase activated receptors (PARs)	5	162.2×	3e-09
G alpha (s) signalling events	5	33.3×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-activating G protein-coupled receptor signaling pathway	5	56.5×	1e-06
G protein-coupled receptor signaling pathway	7	25.4×	2e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

130 predictions. Top by Δscore:

Variant	Effect	Δscore
11:118883992:GGTG:G	donor_loss	1.0000
11:118883993:G:GG	donor_gain	1.0000
11:118883994:TGA:T	donor_loss	1.0000
11:118883989:CCTG:C	donor_gain	0.9900
11:118883991:TG:T	donor_gain	0.9900
11:118883992:GG:G	donor_gain	0.9900
11:118893594:A:AG	acceptor_gain	0.9900
11:118893595:G:GG	acceptor_gain	0.9900
11:118883990:CTG:C	donor_gain	0.9800
11:118883988:ACCTG:A	donor_gain	0.9700
11:118883996:A:AC	donor_loss	0.9700
11:118893595:GTTCT:G	acceptor_gain	0.9400
11:118893590:TTGCA:T	acceptor_loss	0.9300
11:118893591:TGCA:T	acceptor_loss	0.9300
11:118893592:GCAGT:G	acceptor_loss	0.9300
11:118893593:CAG:C	acceptor_loss	0.9300
11:118893594:AG:A	acceptor_loss	0.9300
11:118893595:G:A	acceptor_loss	0.9300
11:118893585:T:A	acceptor_loss	0.9200
11:118893595:GTTC:G	acceptor_gain	0.9000
11:118893595:GTT:G	acceptor_gain	0.8500
11:118894358:T:A	acceptor_gain	0.8500
11:118884008:T:TA	donor_gain	0.8100
11:118884009:A:AA	donor_gain	0.8100
11:118892280:G:GG	donor_gain	0.8000
11:118893595:GT:G	acceptor_gain	0.8000
11:118892279:A:AG	donor_gain	0.7900
11:118892316:C:T	donor_gain	0.7500
11:118883996:A:AG	donor_gain	0.7400
11:118883997:G:GG	donor_gain	0.7400

AlphaMissense

2416 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:118893889:G:C	W115C	0.996
11:118893889:G:T	W115C	0.996
11:118893953:A:C	S137R	0.995
11:118893955:C:A	S137R	0.995
11:118893955:C:G	S137R	0.995
11:118894064:T:A	W174R	0.994
11:118894064:T:C	W174R	0.994
11:118894529:T:C	F329L	0.994
11:118894531:C:A	F329L	0.994
11:118894531:C:G	F329L	0.994
11:118893950:A:C	S136R	0.993
11:118893952:C:A	S136R	0.993
11:118893952:C:G	S136R	0.993
11:118893908:T:A	C122S	0.992
11:118893909:G:C	C122S	0.992
11:118893940:C:A	N132K	0.992
11:118893940:C:G	N132K	0.992
11:118894346:T:C	F268L	0.992
11:118894348:C:A	F268L	0.992
11:118894348:C:G	F268L	0.992
11:118893737:G:C	G65R	0.991
11:118894223:T:C	F227L	0.991
11:118894225:C:A	F227L	0.991
11:118894225:C:G	F227L	0.991
11:118894340:A:C	S266R	0.991
11:118894342:C:A	S266R	0.991
11:118894342:C:G	S266R	0.991
11:118893751:C:A	N69K	0.990
11:118893751:C:G	N69K	0.990
11:118893858:C:G	P105R	0.990

dbSNP variants (sampled 300 via entrez): RS1000099476 (11:118893525 A>G), RS1000178418 (11:118890043 C>T), RS1000198472 (11:118897469 T>A,G), RS1000472098 (11:118889789 C>T), RS1000509450 (11:118885957 C>T), RS1000645241 (11:118886164 C>T), RS1000670131 (11:118897736 G>A,C,T), RS1000691773 (11:118884259 T>C), RS1000771263 (11:118896143 T>C,G), RS1000824363 (11:118891465 A>G), RS1000943197 (11:118891746 C>T), RS1001555680 (11:118898022 G>A), RS1001992802 (11:118892157 G>A,T), RS1002149963 (11:118895332 G>A), RS1002157571 (11:118886441 C>A,G,T)

Disease associations

OMIM: gene MIM:601613 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

35 associations (top):

Study	Trait	p-value
GCST001010_14	Primary biliary cholangitis	3.000000e-12
GCST001198_15	Multiple sclerosis	3.000000e-07
GCST001670_2	Vitiligo	2.000000e-09
GCST001725_16	Inflammatory bowel disease	7.000000e-09
GCST002318_142	Rheumatoid arthritis	1.000000e-17
GCST002318_17	Rheumatoid arthritis	1.000000e-15
GCST002643_2	Follicular lymphoma	6.000000e-20
GCST003129_24	Primary biliary cholangitis	2.000000e-13
GCST003990_14	Allergy	9.000000e-11
GCST004302_5	Primary biliary cholangitis	3.000000e-13
GCST004878_10	Sjögren’s syndrome	1.000000e-08
GCST005038_134	Allergic disease (asthma, hay fever or eczema)	5.000000e-18
GCST005531_4	Multiple sclerosis	3.000000e-15
GCST005531_72	Multiple sclerosis	6.000000e-15
GCST005987_49	Albumin-globulin ratio	2.000000e-09
GCST006409_32	Allergic rhinitis	2.000000e-23
GCST006959_146	Rheumatoid arthritis	1.000000e-13
GCST006959_49	Rheumatoid arthritis	3.000000e-15
GCST007797_4	Asthma onset (childhood vs adult)	4.000000e-12
GCST007798_135	Asthma	7.000000e-12
GCST007800_26	Asthma (childhood onset)	4.000000e-30
GCST007994_20	Asthma (age of onset)	4.000000e-14
GCST007995_32	Asthma (childhood onset)	2.000000e-13
GCST008154_73	Trunk fat mass	6.000000e-06
GCST008644_3	Celiac disease and Rheumatoid arthritis	2.000000e-11
GCST009798_24	Asthma	4.000000e-11
GCST010002_199	Refractive error	3.000000e-34
GCST010042_59	Asthma	2.000000e-17
GCST010043_53	Asthma	2.000000e-18
GCST010984_28	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	2.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004267	biliary liver cirrhosis
EFO:0005128	albumin:globulin ratio measurement
EFO:0004847	age at onset
EFO:0004312	vital capacity
EFO:0011038	anti-human herpes virus 7 antibody measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075315 (SINGLE PROTEIN)

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 (1 total), top 1:

Ligand	Action	Affinity	Parameter
CXCL13	Full agonist	7.3	pKd

Binding affinities (BindingDB)

2 measured of 2 human assays (2 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
N-benzyl-2-[(2S,6S,8E,12S)-12-[(4-fluorophenyl)methyl]-5,13-dioxo-2-phenyl-1-oxa-4-azacyclotridec-8-en-6-yl]-N-(2-hydroxyethyl)acetamide	IC50	1450 nM
SMR001337737	IC50	16900 nM

ChEMBL bioactivities

48 potent at pChembl≥5 of 77 total, top 48 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.30	IC50	5	nM	CHEMBL3719134
8.15	IC50	7	nM	CHEMBL3715759
8.05	IC50	9	nM	CHEMBL3717162
7.96	IC50	11	nM	CHEMBL3718924
7.89	IC50	13	nM	CHEMBL3718468
7.85	IC50	14	nM	CHEMBL3717006
7.82	IC50	15	nM	CHEMBL3716436
7.82	IC50	15	nM	CHEMBL3717871
7.77	IC50	17	nM	CHEMBL3719066
7.64	IC50	23	nM	CHEMBL3719322
7.58	IC50	26	nM	CHEMBL3717912
7.52	IC50	30	nM	CHEMBL3717598
7.48	IC50	33	nM	CHEMBL3717460
7.42	IC50	38	nM	CHEMBL3718117
7.35	IC50	45	nM	CHEMBL3718266
7.33	IC50	47	nM	CHEMBL3716043
7.25	IC50	56	nM	CHEMBL3715092
7.01	IC50	97	nM	CHEMBL3718638
7.00	IC50	99	nM	CHEMBL3718742
6.98	IC50	105	nM	CHEMBL3716140
6.70	IC50	200	nM	CHEMBL3715285
6.63	IC50	232	nM	CHEMBL3716008
6.60	IC50	251.2	nM	CHEMBL5288861
6.57	IC50	268	nM	CHEMBL3716354
6.53	IC50	298	nM	CHEMBL3717606
6.42	IC50	380	nM	CHEMBL3717675
6.35	IC50	446	nM	CHEMBL3716747
6.33	IC50	470	nM	CHEMBL3718851
6.31	IC50	493	nM	CHEMBL3715720
6.27	IC50	533	nM	CHEMBL3716359
6.27	IC50	537	nM	CHEMBL3717130
6.17	IC50	675	nM	CHEMBL3717266
5.98	IC50	1050	nM	CHEMBL3715904
5.97	IC50	1080	nM	CHEMBL3717337
5.64	IC50	2300	nM	CHEMBL3716634
5.54	IC50	2850	nM	CHEMBL3719127
5.53	IC50	2930	nM	CHEMBL3715405
5.44	IC50	3650	nM	CHEMBL3718418
5.41	IC50	3870	nM	CHEMBL3716277
5.26	IC50	5450	nM	CHEMBL3715707
5.21	IC50	6100	nM	CHEMBL3719362
5.16	IC50	7002	nM	CHEMBL1382320
5.11	IC50	7800	nM	CHEMBL3714985
5.09	IC50	8200	nM	CHEMBL3718838
5.03	IC50	9239	nM	CHEMBL1443778
5.03	IC50	9374	nM	CHEMBL1437683
5.02	IC50	9500	nM	CHEMBL3717257
5.02	IC50	9456	nM	CHEMBL1875956

PubChem BioAssay actives

1 with measured affinity, of 92 total; 1 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-(oxan-4-yl)-[[4-[(3-phenyl-8,9-dihydro-7H-benzo[7]annulene-6-carbonyl)amino]phenyl]methyl]azanium chloride	1953225: Antagonist activity at CXCR5 (unknown origin)	ic50	0.2512	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, affects methylation, affects reaction	3
Tretinoin	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, increases expression	2
Arsenic	affects expression, affects cotreatment, decreases expression	2
triphenyl phosphate	affects expression	1
sulforaphane	increases expression	1
butyraldehyde	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
pentanal	decreases expression	1
fumonisin B1	decreases expression	1
tamibarotene	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
pevonedistat	affects expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Aripiprazole	increases expression, affects cotreatment	1
Ascorbic Acid	affects cotreatment, increases expression	1
Calcium	affects abundance	1
Fluorides	affects cotreatment, decreases expression	1
Lead	decreases expression	1
Ozone	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Zearalenone	increases expression	1
Endocannabinoids	affects binding, decreases reaction, increases activity	1

ChEMBL screening assays

33 unique, capped per target: 21 binding, 12 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1120200	Functional	Antagonist activity at human CXCR5 expressed in mouse L1.2 cells assessed as inhibition of CXCL13-induced chemotaxis up to 10 uM after 4 hrs	Discovery of a novel series of CXCR3 antagonists. — Bioorg Med Chem Lett
CHEMBL1953534	Binding	Inhibition of CXCR5 at 1 uM	Discovery of INCB3284, a Potent, Selective, and Orally Bioavailable hCCR2 Antagonist. — ACS Med Chem Lett

Cellosaurus cell lines

6 cell lines: 4 spontaneously immortalized cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1BQ	Abcam Raji CXCR5 KO	Cancer cell line	Male
CVCL_KA17	CHO-K1/Galpha15/CXCR5	Spontaneously immortalized cell line	Female
CVCL_KV04	cAMP Hunter CHO-K1 CXCR5 Gi	Spontaneously immortalized cell line	Female
CVCL_KW19	PathHunter C2C12 CXCR5 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KW80	PathHunter CHO-K1 CXCR5 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_RQ22	PathHunter U2OS CXCR5 beta-arrestin	Cancer cell line	Female

Clinical trials (associated diseases)

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