CXCL11

Summary

CXCL11 (C-X-C motif chemokine ligand 11, HGNC:10638) is a protein-coding gene on chromosome 4q21.1, encoding C-X-C motif chemokine 11 (O14625). Chemotactic for interleukin-activated T-cells but not unstimulated T-cells, neutrophils or monocytes.

Chemokines are a group of small (approximately 8 to 14 kD), mostly basic, structurally related molecules that regulate cell trafficking of various types of leukocytes through interactions with a subset of 7-transmembrane, G protein-coupled receptors. Chemokines also play fundamental roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system as well as on endothelial cells involved in angiogenesis or angiostasis. Chemokines are divided into 2 major subfamilies, CXC and CC. This antimicrobial gene is a CXC member of the chemokine superfamily. Its encoded protein induces a chemotactic response in activated T-cells and is the dominant ligand for CXC receptor-3. The gene encoding this protein contains 4 exons and at least three polyadenylation signals which might reflect cell-specific regulation of expression. IFN-gamma is a potent inducer of transcription of this gene. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6373 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• MANE Select transcript: NM_005409

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10638
Approved symbol	CXCL11
Name	C-X-C motif chemokine ligand 11
Location	4q21.1
Locus type	gene with protein product
Status	Approved
Aliases	H174, b-R1, I-TAC, IP-9
Ensembl gene	ENSG00000169248
Ensembl biotype	protein_coding
OMIM	604852
Entrez	6373

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000306621, ENST00000503860

RefSeq mRNA: 2 — MANE Select: NM_005409 NM_001302123, NM_005409

CCDS: CCDS3574

Canonical transcript exons

ENST00000306621 — 4 exons

Exon	Start	End
ENSE00001126433	76035047	76035119
ENSE00001126440	76035927	76036070
ENSE00001139458	76033682	76034816
ENSE00001139467	76035216	76035342

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 77.15.

FANTOM5 (CAGE): breadth broad, TPM avg 18.9538 / max 4201.1888, expressed in 266 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52637	18.9538	266

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.15	gold quality
vermiform appendix	UBERON:0001154	75.93	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	72.75	gold quality
body of pancreas	UBERON:0001150	72.72	gold quality
lymph node	UBERON:0000029	71.61	gold quality
rectum	UBERON:0001052	71.35	gold quality
caecum	UBERON:0001153	70.07	gold quality
pancreas	UBERON:0001264	67.82	gold quality
smooth muscle tissue	UBERON:0001135	64.34	gold quality
islet of Langerhans	UBERON:0000006	62.73	gold quality
monocyte	CL:0000576	61.91	gold quality
mononuclear cell	CL:0000842	61.80	gold quality
leukocyte	CL:0000738	61.73	gold quality
calcaneal tendon	UBERON:0003701	61.05	gold quality
palpebral conjunctiva	UBERON:0001812	60.81	gold quality
spleen	UBERON:0002106	60.68	gold quality
nasal cavity mucosa	UBERON:0001826	59.72	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	59.38	gold quality
gall bladder	UBERON:0002110	58.74	gold quality
superficial temporal artery	UBERON:0001614	58.53	gold quality
upper lobe of left lung	UBERON:0008952	57.75	gold quality
spinal cord	UBERON:0002240	57.54	gold quality
upper lobe of lung	UBERON:0008948	57.00	gold quality
granulocyte	CL:0000094	56.70	gold quality
right lung	UBERON:0002167	56.43	gold quality
lung	UBERON:0002048	55.46	gold quality
nasal cavity epithelium	UBERON:0005384	55.19	silver quality
pancreatic ductal cell	CL:0002079	54.41	silver quality
amygdala	UBERON:0001876	54.23	gold quality
pericardium	UBERON:0002407	53.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-8	yes	1302.10
E-ANND-3	yes	3.88

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BCL6, HAND1, IRF1, IRF2, NFKB1, NFKB, PPARG, RELA, STAT1, STAT3, TBPL1

miRNA regulators (miRDB)

73 targeting CXCL11, 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-9-5P	100.00	72.28	2361
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337

Literature-anchored findings (GeneRIF, showing 40)

• chemotactic activity for CXCR3-expressing cells; substrate for dipeptidylpeptidase IV (PMID:11559369)
• I-TAC is a highly potent chemoattractant of normal blood CD4 and CD8 T cell transendothelial migration and a major mediator of blood memory T lymphocyte migration to inflammation. (PMID:12055261)
• The IFN-gamma-inducible T cell alpha-chemoattractant was induced in human brain microvascular endothelial cells and astrocytes only after inflammatory stimuli. (PMID:12162873)
• These data suggest that IFN-beta acts through PI3K to enhance the transactivation competence of NF-kappa B complexes through phosphorylation of p65 within the TAD of beta-R1. (PMID:12169689)
• Levels of ITAC/CXCL11 were found elevated in patients with severe transplantation coronary artery disease (TCAD) compared with long-term survivors of transplantation without TCAD and healthy volunteers who had not undergone transplantation (PMID:12695288)
• increased calpain activity in undifferentiated keratinocytes. inhibited calpain activity in fibroblasts. redifferentiated basal keratinocytes limit fibroblast repopulation of dermis of healed wounds while promoting re-epithelialization. (PMID:12787142)
• A higher amount of I-TAC mRNA is expressed after exposure of keratinocytes to interferon-gamma, leading to migration of T cells from the dermis to the epidermis and representing a second step of chemotaxis following T cell recruitment from blood. (PMID:12847282)
• CXCR3 ligands inhibit CCR3-mediated functional responses of both human eosinophils and CCR3 transfectants induced by all three eotaxins, with CXCL11 being the most efficacious antagonist. (PMID:12884299)
• CXCL11 displays antimicrobial activity against E. coli and S. aureus. (PMID:12949249)
• I-TAC, one of the most potent chemoattractants for activated T cells, is produced by hepatocytes in the HCV-infected liver and plays an important role in T cell recruitment and ultimately the pathogenesis of chronic hepatitis C (PMID:15122750)
• CXCL9, CXCL10, and CXCL11 functions are mediated by intracellular domains of CXCR3 (PMID:15150261)
• ductal epithelial cells produce I-TAC proteins in response to stimulation with IFNgamma secreted by lymphocytes (PMID:15308116)
• novel I-TAC -599del5 promoter polymorphism is a functional variant in the presence of replicating HCV and may predispose to HCV disease susceptibility. (PMID:15653416)
• recruitment might enhance the sequestration of T cells in infected lymphoid organs and the spread of infection between cells, contributing to the immunopathology of AIDS (PMID:15814716)
• CXCL11 creates a chemokine gradient between the cerebrospinal fluid (CSF) and serum and recruits CXCR3-expressing memory CD4+ T-cells into the CSF of neuroborreliosis patients. (PMID:15885315)
• autocrine-acting CXCL11 mediates, at least in part, the regulations of osteoclastogenesis by type I interferons (PMID:16081539)
• Increased expression of the interferon-induced angiostatic ELR- CXC chemokines is a feature of juvenile DM that parallels the degree of vasculopathy in patients with the disease (PMID:16200621)
• This CSCR3 ligand has the ability to activate biochemical (e.g., PtdIns and MAP kinase activation) and functional events (actin reorganization) in intestinal myofibroblasts. (PMID:16210647)
• Increased I-TAC levels in blood and cerebrospinal fluid is associated with Lyme borreliosis (PMID:16358960)
• CXCL11-dependent CXCR3 internalization and cell migration are regulated by the CXCR3 membrane proximal carboxyl terminus, whereas adhesion is regulated by the 3i loop S245. (PMID:16368892)
• IFN-gamma promotes implantation by stimulating EEC to produce CXCL11, which induces migration of trophoblast cells and T cells, proliferation of ESC, and apoptosis of EEC. (PMID:17142784)
• prolactin may enhance IFN-gamma-induced CXCL9, CXCL10, and CXCL11 production in keratinocytes (PMID:17255201)
• CD13 rapidly processed CXCL11, but not CXCL8, to generate truncated CXCL11 forms that had reduced binding, signaling, and chemotactic properties for lymphocytes and CXCR3- or CXCR7-transfected cells. (PMID:17363734)
• Egression of human T cells across the bronchial epithelium is a multistep process, driven in part by a polarized transepithelial gradient of CXCL11 that is up-regulated in patients with chronic obstructive airways disease. (PMID:18209084)
• Data show that RIG-I mRNA and protein are expressed in HeLa cells stimulated with IFN-gamma, and that RNA interference against RIG-I results in the suppression of IFN-gamma-induced CXCL11 expression. (PMID:18258269)
• DP8 cleavage of the N-terminal two residues of IP10 (CXCL10), ITAC (CXCL11) and SDF-1 (CXCL12), is reported. (PMID:18275857)
• CXCL-11 is targeted by ebv-mir-BHRF1-3 in primary lymphomas (PMID:18316607)
• potential new roles in down-regulating Th1 lymphocyte chemoattraction through MMP processing of CXCL11. (PMID:18411283)
• There are elevated concentrations of the chemokines MDC, eotaxin, I-TAC, and MCP-1 in malignant pleural effusions. (PMID:18515987)
• These data provide new structure-function dimensions for chemokines in leukocyte mobilization, disclosing an anti-inflammatory role for PAD. (PMID:18645041)
• IP-9 is a key ligand in the CXCR3 signaling system for wound repair (PMID:18669615)
• Development of allergic disease is associated with a more marked Th2-like deviation already at birth, shown as increased levels of cord blood IgE and MDC (CCL22) and higher ratios of MDC (CCL22) to IP-10 (CXCL10) and I-TAC (CXCL11). (PMID:19175890)
• SpeB destroys most of the signaling and antibacterial properties of chemokines expressed by an inflamed epithelium. (PMID:19274094)
• The three-dimensional structure of CXCL9 and CXCR3, and, successively, of the CXCL9/CXCR3 complex were modelled in comparison to CXCL10/CXCR3 and CXCL11/CXCR3 complexes. (PMID:19800124)
• Studies indicate that I-TAC-targeted intervening strategies would have potential application for the alleviation of acute transplant rejection. (PMID:19875106)
• TNFSF14 enhanced IFN-gamma-induced secretion of CXCL10 and CXCL11 from human gingival fibroblasts. (PMID:19939453)
• Studies indicate that CXCR7 is an interceptor for CXCL12 and CXCL11. (PMID:20036838)
• The expression and function of CXCR3 and CXCR7 receptors in cervical carcinoma, rhabdomyosarcoma and glioblastoma cell lines, was evaluated. (PMID:20529825)
• A potent dose-dependent inhibition by PPARalpha-agonists was observed on the cytokines-stimulated secretion of CXCL11 in Graves disease and in primary thyrroid culture. (PMID:20810571)
• involved in microbial-induced intestinal inflammation and Th17 cell development in ulcerative colitis (PMID:21438871)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
rattus_norvegicus	Cxcl11	ENSRNOG00000022298

Paralogs (12): CXCL2 (ENSG00000081041), PF4V1 (ENSG00000109272), CXCL6 (ENSG00000124875), CXCL9 (ENSG00000138755), CXCL13 (ENSG00000156234), CXCL3 (ENSG00000163734), CXCL5 (ENSG00000163735), PPBP (ENSG00000163736), PF4 (ENSG00000163737), CXCL1 (ENSG00000163739), CXCL10 (ENSG00000169245), CXCL8 (ENSG00000169429)

Protein

Protein identifiers

C-X-C motif chemokine 11 — O14625 (reviewed: O14625)

Alternative names: Beta-R1, H174, Interferon gamma-inducible protein 9, Interferon-inducible T-cell alpha chemoattractant, Small-inducible cytokine B11

All UniProt accessions (1): O14625

UniProt curated annotations — full annotation on UniProt →

Function. Chemotactic for interleukin-activated T-cells but not unstimulated T-cells, neutrophils or monocytes. Induces calcium release in activated T-cells. Binds to CXCR3. May play an important role in CNS diseases which involve T-cell recruitment. May play a role in skin immune responses.

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

Subcellular location. Secreted.

Tissue specificity. High levels in peripheral blood leukocytes, pancreas and liver astrocytes. Moderate levels in thymus, spleen and lung. Low levels in placenta, prostate and small intestine. Also found in epidermal basal layer keratinocytes in skin disorders.

Induction. By IFNG/IFN-gamma and IFNB1/IFN-beta. Induction by IFNG/IFN-gamma is enhanced by TNF in monocytes, dermal fibroblasts and endothelial cells, and by IL1/interleukin-1 in astrocytes.

Similarity. Belongs to the intercrine alpha (chemokine CxC) family.

RefSeq proteins (2): NP_001289052, NP_005400* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001089	Chemokine_CXC	Family
IPR001811	Chemokine_IL8-like_dom	Domain
IPR018048	Chemokine_CXC_CS	Conserved_site
IPR033899	CXC_Chemokine_domain	Domain
IPR036048	Interleukin_8-like_sf	Homologous_superfamily
IPR039809	Chemokine_b/g/d	Family

Pfam: PF00048

UniProt features (15 total): strand 4, sequence conflict 3, helix 2, disulfide bond 2, signal peptide 1, chain 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9P0M	ELECTRON MICROSCOPY	2.95
8HNK	ELECTRON MICROSCOPY	3.01
1RJT	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14625-F1	79.75	0.00

Antibody-complex structures (SAbDab): 1 — 8HNK

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 27

Disulfide bonds (2): 30–57, 32–74

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: 334 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, CREL_01, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, MODULE_64, GAURNIER_PSMD4_TARGETS, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_LEUKOCYTE_CHEMOTAXIS, HINATA_NFKB_TARGETS_KERATINOCYTE_UP, GOBP_POSITIVE_REGULATION_OF_RELEASE_OF_SEQUESTERED_CALCIUM_ION_INTO_CYTOSOL

GO Biological Process (11): chemotaxis (GO:0006935), inflammatory response (GO:0006954), immune response (GO:0006955), signal transduction (GO:0007165), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), cell-cell signaling (GO:0007267), T cell chemotaxis (GO:0010818), regulation of cell population proliferation (GO:0042127), positive regulation of release of sequestered calcium ion into cytosol (GO:0051281), chemokine-mediated signaling pathway (GO:0070098), defense response (GO:0006952)

GO Molecular Function (6): chemokine activity (GO:0008009), heparin binding (GO:0008201), CXCR chemokine receptor binding (GO:0045236), CXCR3 chemokine receptor binding (GO:0048248), cytokine activity (GO:0005125), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), 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
cell communication	2
signaling	2
regulation of cellular process	2
chemokine receptor binding	2
cellular anatomical structure	2
response to chemical	1
taxis	1
defense response	1
immune system process	1
response to stimulus	1
cellular process	1
cellular response to stimulus	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
lymphocyte chemotaxis	1
T cell migration	1
cell population proliferation	1
release of sequestered calcium ion into cytosol	1
regulation of release of sequestered calcium ion into cytosol	1
positive regulation of calcium ion transmembrane transport	1
G protein-coupled receptor signaling pathway	1
cytokine-mediated signaling pathway	1
cellular response to chemokine	1
response to stress	1
cytokine activity	1
cell chemotaxis	1
glycosaminoglycan binding	1
sulfur compound binding	1
CXCR chemokine receptor binding	1
receptor ligand activity	1
binding	1

Protein interactions and networks

STRING

2322 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CXCL11	CXCR3	P49682	999
CXCL11	ACKR3	P25106	997
CXCL11	CXCR4	P30991	983
CXCL11	CCR5	P51681	970
CXCL11	CXCL5	P42830	956
CXCL11	PF4	P02776	956
CXCL11	CXCL6	P80162	949
CXCL11	TGFB1	P01137	947
CXCL11	CXCL3	P19876	927
CXCL11	IFNA13	P01562	893
CXCL11	CXCL8	P10145	893
CXCL11	CXCL2	P19875	893
CXCL11	CCL5	P13501	885
CXCL11	PPBP	P02775	878
CXCL11	CXCL12	P48061	863

IntAct

39 interactions, top by confidence:

A	B	Type	Score
CXCL11	DPP4	psi-mi:“MI:0407”(direct interaction)	0.620
DPP4	CXCL11	psi-mi:“MI:0194”(cleavage reaction)	0.620
MTUS2	CXCL11	psi-mi:“MI:0915”(physical association)	0.560
CXCL11	MTUS2	psi-mi:“MI:0915”(physical association)	0.560
CXCL11	CCL5	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL11	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL11	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
PF4	CXCL11	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL12	CXCL11	psi-mi:“MI:0407”(direct interaction)	0.560
TNFAIP6	CXCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL11	CCL8	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL11	CCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL11	CCL13	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL11	CCL24	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL11	CCL26	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL11	XCL1	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL11	PF4V1	psi-mi:“MI:0407”(direct interaction)	0.440
CCL1	CXCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CCL13	CXCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CCL20	CXCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CCL21	CXCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CCL24	CXCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CCL25	CXCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CCL26	CXCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL2	CXCL11	psi-mi:“MI:0407”(direct interaction)	0.440
PF4V1	CXCL11	psi-mi:“MI:0407”(direct interaction)	0.440
PPBP	CXCL11	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (29): MTUS2 (Two-hybrid), CXCL11 (Two-hybrid), CXCL11 (Reconstituted Complex), CXCL11 (Reconstituted Complex), CXCL11 (Reconstituted Complex), CXCL11 (Reconstituted Complex), CXCL11 (Reconstituted Complex), CXCL11 (Reconstituted Complex), CXCL11 (Reconstituted Complex), CXCL11 (Reconstituted Complex), CXCL11 (Reconstituted Complex), CXCL11 (Reconstituted Complex), CCL11 (Reconstituted Complex), CCL13 (Reconstituted Complex), CCL24 (Reconstituted Complex)

ESM2 similar proteins: A9QWQ1, O14625, O46675, O46676, O46677, O46678, O89098, O97919, P08317, P09340, P09341, P10147, P10855, P10889, P12850, P13236, P13501, P14095, P14097, P16619, P19875, P19876, P30782, P30882, P42831, P46632, P47854, P50229, P50230, P50231, P97272, Q17QA1, Q5EBF6, Q5I1Z0, Q5RA36, Q68A92, Q68AZ0, Q711P4, Q8HYQ1, Q8HYQ2

Diamond homologs: A0A0R4INB9, A9QWP9, A9QWQ1, B0R191, O14625, O46678, P02775, P02778, P08317, P09341, P12850, P17515, P19875, P19876, P22952, P42830, P48973, P50228, P80162, P80221, P82535, P97885, Q07325, Q2KIQ8, Q5KSV9, Q865F5, Q8MIZ1, Q9JHH5, O46675, O46676, O46677, O55038, P18340, P47854, P09340, Q8MIN2, P43030, P02776, P10720, P30034

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CXCL11	“up-regulates activity”	CXCR3	binding
CXCL11	“up-regulates activity”	ACKR3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 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
Chemokine receptors bind chemokines	14	137.9×	2e-27
Class A/1 (Rhodopsin-like receptors)	8	31.2×	8e-10
Peptide ligand-binding receptors	8	31.2×	8e-10
GPCR ligand binding	8	27.0×	2e-09
G alpha (i) signalling events	12	24.6×	7e-14
Signaling by GPCR	8	16.9×	7e-08
GPCR downstream signalling	7	16.0×	9e-07

GO biological processes:

GO term	Partners	Fold	FDR
eosinophil chemotaxis	9	274.8×	2e-19
chemokine-mediated signaling pathway	13	175.5×	4e-25
positive regulation of T cell migration	5	152.6×	5e-09
antimicrobial humoral immune response mediated by antimicrobial peptide	14	94.5×	2e-23
chemotaxis	14	79.3×	1e-22
neutrophil chemotaxis	6	71.4×	6e-09
cell chemotaxis	8	61.7×	2e-11
intracellular calcium ion homeostasis	6	36.3×	3e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

245 predictions. Top by Δscore:

Variant	Effect	Δscore
4:76035040:AACTT:A	donor_loss	1.0000
4:76035041:ACTT:A	donor_loss	1.0000
4:76035042:CTT:C	donor_loss	1.0000
4:76035043:TTAC:T	donor_loss	1.0000
4:76035044:TACT:T	donor_loss	1.0000
4:76035045:A:AC	donor_gain	1.0000
4:76035045:A:T	donor_loss	1.0000
4:76035046:C:CA	donor_gain	1.0000
4:76035046:CT:C	donor_gain	1.0000
4:76035046:CTTTG:C	donor_gain	1.0000
4:76035115:TAATA:T	acceptor_gain	1.0000
4:76035116:AATA:A	acceptor_gain	1.0000
4:76035117:ATA:A	acceptor_gain	1.0000
4:76035117:ATAC:A	acceptor_loss	1.0000
4:76035118:TA:T	acceptor_gain	1.0000
4:76035118:TAC:T	acceptor_loss	1.0000
4:76035119:AC:A	acceptor_loss	1.0000
4:76035120:C:CC	acceptor_gain	1.0000
4:76035121:T:C	acceptor_loss	1.0000
4:76035210:A:AC	donor_gain	1.0000
4:76035211:C:CC	donor_gain	1.0000
4:76035211:CT:C	donor_loss	1.0000
4:76035212:T:TC	donor_loss	1.0000
4:76035213:T:TC	donor_loss	1.0000
4:76035214:A:AC	donor_gain	1.0000
4:76035214:AC:A	donor_loss	1.0000
4:76035214:ACAT:A	donor_gain	1.0000
4:76035215:C:CA	donor_gain	1.0000
4:76035215:CAT:C	donor_gain	1.0000
4:76035215:CATC:C	donor_gain	1.0000

AlphaMissense

620 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:76035117:A:T	I64N	0.932
4:76035087:C:G	C74S	0.920
4:76035088:A:T	C74S	0.920
4:76035309:C:G	C32S	0.906
4:76035310:A:T	C32S	0.906
4:76035073:A:G	S79P	0.903
4:76035310:A:G	C32R	0.890
4:76035088:A:G	C74R	0.889
4:76035117:A:C	I64S	0.889
4:76035064:C:G	A82P	0.888
4:76035234:C:G	C57S	0.884
4:76035235:A:T	C57S	0.884
4:76035084:A:G	L75P	0.877
4:76035315:C:G	C30S	0.874
4:76035316:A:T	C30S	0.874
4:76035219:A:T	V62E	0.862
4:76035316:A:G	C30R	0.858
4:76035084:A:T	L75Q	0.852
4:76035221:T:A	E61D	0.850
4:76035221:T:G	E61D	0.850
4:76035308:G:C	C32W	0.838
4:76035107:T:A	K67N	0.835
4:76035107:T:G	K67N	0.835
4:76035233:A:C	C57W	0.834
4:76035235:A:G	C57R	0.830
4:76035090:C:G	R73P	0.829
4:76035270:A:T	I45N	0.823
4:76035065:T:A	Q81H	0.822
4:76035065:T:G	Q81H	0.822
4:76035309:C:T	C32Y	0.822

dbSNP variants (sampled 300 via entrez): RS1000137559 (4:76036210 T>C), RS10003240 (4:76034177 C>A,G,T), RS10003382 (4:76034320 C>A,G,T), RS1000490673 (4:76034281 A>G), RS1001478869 (4:76035324 CTT>C,CTTT), RS1001697955 (4:76036648 T>C), RS10017431 (4:76034253 T>A,C,G), RS1001939834 (4:76035419 G>A,C,T), RS10021313 (4:76036090 T>C), RS1002509331 (4:76034202 G>A,T), RS10025102 (4:76034205 G>A), RS1002583636 (4:76035669 A>G,T), RS1003099155 (4:76038044 T>C), RS10031983 (4:76036918 G>C), RS1006432543 (4:76036933 T>C)

Disease associations

OMIM: gene MIM:604852 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006585_1084	Blood protein levels	3.000000e-13
GCST006622_14	Neonatal cytokine/chemokine levels (fetal genetic effect)	2.000000e-14
GCST007009_3	Hippocampal volume	7.000000e-07
GCST007009_4	Hippocampal volume	3.000000e-07

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004747	protein measurement
EFO:0007959	fetal genotype effect measurement
EFO:0008057	C-X-C motif chemokine 11 measurement
EFO:0005035	hippocampal volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression, increases expression, decreases reaction	3
Lipopolysaccharides	decreases reaction, increases expression, affects cotreatment	3
1-nitropyrene	increases expression	2
ruxolitinib	decreases reaction, increases expression, decreases expression	2
Benzo(a)pyrene	increases expression	2
Calcitriol	decreases expression, increases expression, affects cotreatment	2
Formaldehyde	decreases expression, increases expression	2
Nickel	increases expression	2
Progesterone	increases expression, affects cotreatment	2
Silicon Dioxide	increases expression	2
Tetrachlorodibenzodioxin	affects expression, increases expression	2
Nanotubes, Carbon	increases expression	2
Particulate Matter	decreases expression, decreases reaction, increases abundance, increases expression	2
Soot	increases expression	2
peracetylated N-azidoacetylmannosamine	decreases expression	1
TL8-506	affects cotreatment, increases expression, increases secretion	1
22-hydroxycholesterol	increases expression	1
deoxynivalenol	increases expression	1
titanium dioxide	increases expression	1
zinc chloride	increases expression	1
sodium arsenite	decreases expression	1
ferrous sulfate	increases expression	1
nickel chloride	decreases reaction, increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression, decreases reaction	1
3-aminofluoranthene	increases expression	1
fumonisin B1	increases expression	1
gadodiamide	increases expression, increases secretion	1
perfluorooctane sulfonic acid	decreases reaction, increases expression, decreases expression	1
monomethylarsonous acid	affects expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8EA	Abcam HCT 116 CXCL11 KO	Cancer cell line	Male
CVCL_C0BH	Abcam A-549 CXCL11 KO	Cancer cell line	Male
CVCL_D2EP	Abcam MCF-7 CXCL11 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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