CXCL12

Summary

CXCL12 (C-X-C motif chemokine ligand 12, HGNC:10672) is a protein-coding gene on chromosome 10q11.21, encoding Stromal cell-derived factor 1 (P48061). Chemoattractant active on T-lymphocytes and monocytes but not neutrophils.

This antimicrobial gene encodes a stromal cell-derived alpha chemokine member of the intercrine family. The encoded protein functions as the ligand for the G-protein coupled receptor, chemokine (C-X-C motif) receptor 4, and plays a role in many diverse cellular functions, including embryogenesis, immune surveillance, inflammation response, tissue homeostasis, and tumor growth and metastasis. Mutations in this gene are associated with resistance to human immunodeficiency virus type 1 infections. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6387 — RefSeq curated summary.

At a glance

• GWAS associations: 40
• Clinical variants (ClinVar): 56 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_199168

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10672
Approved symbol	CXCL12
Name	C-X-C motif chemokine ligand 12
Location	10q11.21
Locus type	gene with protein product
Status	Approved
Aliases	SCYB12, SDF-1a, SDF-1b, PBSF, TLSF-a, TLSF-b, TPAR1
Ensembl gene	ENSG00000107562
Ensembl biotype	protein_coding
OMIM	600835
Entrez	6387

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000343575, ENST00000374426, ENST00000374429, ENST00000395793, ENST00000395794, ENST00000488591, ENST00000496375

RefSeq mRNA: 5 — MANE Select: NM_199168 NM_000609, NM_001033886, NM_001178134, NM_001277990, NM_199168

CCDS: CCDS31186, CCDS44373, CCDS53527, CCDS60518, CCDS7207

Canonical transcript exons

ENST00000343575 — 3 exons

Exon	Start	End
ENSE00001234815	44377067	44378723
ENSE00003543907	44380763	44380880
ENSE00003730278	44384945	44385097

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 99.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 97.7335 / max 4579.5734, expressed in 1178 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109209	96.8678	1176
109193	0.8657	339

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
synovial joint	UBERON:0002217	99.75	gold quality
pericardium	UBERON:0002407	99.74	gold quality
mammary duct	UBERON:0001765	99.59	gold quality
skin of hip	UBERON:0001554	99.52	gold quality
trabecular bone tissue	UBERON:0002483	99.41	gold quality
parietal pleura	UBERON:0002400	99.40	gold quality
layer of synovial tissue	UBERON:0007616	99.35	gold quality
superficial temporal artery	UBERON:0001614	99.28	gold quality
gall bladder	UBERON:0002110	99.20	gold quality
vena cava	UBERON:0004087	99.13	gold quality
upper arm skin	UBERON:0004263	99.10	gold quality
thoracic mammary gland	UBERON:0005200	99.09	gold quality
nipple	UBERON:0002030	99.05	gold quality
mammary gland	UBERON:0001911	99.02	gold quality
upper leg skin	UBERON:0004262	98.97	gold quality
mammalian vulva	UBERON:0000997	98.82	gold quality
penis	UBERON:0000989	98.81	gold quality
epithelium of mammary gland	UBERON:0003244	98.81	gold quality
adipose tissue	UBERON:0001013	98.79	gold quality
lymph node	UBERON:0000029	98.75	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.75	gold quality
omental fat pad	UBERON:0010414	98.72	gold quality
peritoneum	UBERON:0002358	98.71	gold quality
adult organism	UBERON:0007023	98.68	gold quality
caecum	UBERON:0001153	98.59	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.57	gold quality
connective tissue	UBERON:0002384	98.53	gold quality
body of uterus	UBERON:0009853	98.51	gold quality
spleen	UBERON:0002106	98.45	gold quality
colonic epithelium	UBERON:0000397	98.43	gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	20959.52
E-CURD-112	yes	10692.40
E-MTAB-8142	yes	5809.35
E-MTAB-8322	yes	5603.79
E-HCAD-11	yes	1147.91
E-MTAB-9906	yes	1134.28
E-MTAB-10137	yes	472.70
E-MTAB-8410	yes	69.76
E-HCAD-10	yes	45.71
E-MTAB-3929	yes	35.98
E-MTAB-10553	yes	32.16
E-CURD-46	yes	26.59
E-MTAB-10287	yes	20.45
E-GEOD-81547	yes	20.04
E-HCAD-9	yes	16.62

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CCDC62, CEBPA, CEBPB, CTNNB1, DNMT1, DNMT3B, EBF1, EGR1, ESR1, ETV5, FOS, FOXC1, FOXF2, FOXO3, HIF1A, HMGA1, JUN, MYB, MYC, NFKB1, NFKB, PARP1, RELA, RELB, SMAD1, SMAD4, SNAI2, SP1, STAT3, TCF7L2, TP53, TWIST1, YY1

miRNA regulators (miRDB)

166 targeting CXCL12, 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-3646	100.00	73.56	5283
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6744-5P	99.93	66.82	748

Literature-anchored findings (GeneRIF, showing 40)

• SDF1 is involved in astrocyte division and MAP kinase signal transduction. (PMID:11389173)
• Association of stromal cell-derived factor 1 genotype with disease progression of HIV infection (PMID:11709782)
• exerts an antiapoptotic effect on CD34(+) hematopoietic progenitor cells through an autocrine/paracrine regulatory loop (PMID:11830456)
• the presence of the SDF-1 3’A gene correlates with accelerated disease progression in HIV-1-infected children born to seropositive mothers but does not protect against mother-to-child HIV-1 transmission (PMID:11865429)
• elastase-mediated proteolysis of SDF-1/CXCR4 is part of a mechanism regulating their biological functions in both homeostatic and pathologic processes (PMID:11867624)
• These findings support a pivotal role for HEC-expressed CXCL12 and its receptor on T cells in the regulation of T lymphocyte homing to lymph nodes. (PMID:11870628)
• B-cell chemotaxis responsiveness to SDF-1alpha is profoundly suppressed by surrogate antigen. (PMID:11877260)
• SDF1 is expressed in medullar epithelial cells forming Hassall’s corpuscles and demonstrates a potential role in the elimination of apoptotic thymocytes in normal and HIV-1-infected thymic tissues. (PMID:11884424)
• The frequencies of SDF1 mutation associated with the development of clinical symptoms upon infection with human immunodeficiency virus type 1 (HIV-1) were determined in a cohort of individuals from Moscow (PMID:11898620)
• Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone. (PMID:11912162)
• Regulation of endothelial cell branching morphogenesis (PMID:11929756)
• CXCR4/CXCL12 expression and signalling in kidney cancer (PMID:11953881)
• Up-regulation by SDF-1 alpha of lymphocyte adhesion mediated by integrin alpha 4 beta 7 could contribute to lymphocyte homing to mucosa-associated lymphoid tissues. (PMID:11994484)
• leukemic Philadelphia chromosome-positive (Ph+)CD34+ cells from newly diagnosed CML patients that express the chemokine receptor CXCR4 migrate in response to stromal-derived factor-1 (SDF-1) (PMID:12004084)
• role in HIV-1 entry (PMID:12034737)
• induced transient activation of ERK1/2, ribosomal S6 kinase (p90RSK) and Akt, molecules implicated in cell survival. SDF1A also acted synergistically with other cyotkines. (PMID:12036856)
• Lck is required for stromal cell-derived factor 1 alpha (CXCL12)-induced lymphoid cell chemotaxis. (PMID:12036857)
• SDF-1alpha may play a role in the neuronal response to HIV in the brains of AIDS patients. (PMID:12044982)
• SDF-1/CXCL12 upregulated T-cell activation, and a G-coupled protein mediated signaling pathway was necessary for stimulation of T cells by CXCL12. (PMID:12088413)
• Activation of Wiskott-Aldrich syndrome protein and its association with other proteins by stromal cell-derived factor-1alpha is associated with cell migration in Jurkat cells, a T-lymphocyte line. (PMID:12135674)
• The stimulating effect of GAGs was caused by the formation of a stable haptotactic SDF-1 gradient, as SDF-1 bound to immobilized GAGs and triggered HSC migration. Dimerization of presented SDF-1 or increased binding to CXCR4 are possible mechanisms. (PMID:12149427)
• CCR5-binding chemokines modulate induced responses of progenitor B cells in human bone marrow through heterologous desensitization of the CXCR4 chemokine receptor. (PMID:12239139)
• signaling is active in rhabdomyosarcoma cells and regulates locomotion, chemotaxis, and adhesion (PMID:12239174)
• beta-arrestin2 can function not only as a regulator of CXCR4 signaling but also as a mediator of stromal cell-derived factor 1alpha-induced chemotaxis, via the ASK1/p38 MAPK pathway (PMID:12370187)
• Role of the intracellular domains of CXCR4 in SDF-1-mediated signaling (PMID:12393663)
• migration of murine and human IFN-producing cells to CXCR3 ligands in vitro requires engagement of CXCR4 by CXCL12 (PMID:12444109)
• SDF-1alpha plays an important regulatory role in the altered B-cell responses seen in HIV-1 infection. (PMID:12482395)
• expressed in human brain tumors and is involved in glial proliferation in vitro (PMID:12485835)
• results indicate that normal human hematopoietic stem and progenitor cells express functional C3aR and that the C3aR-C3a axis sensitizes the responses of these cells to SDF-1 (PMID:12511407)
• In human bone marrow, CXCL12 triggers a sustained adhesion response specifically in progenitor (pro- and pre-) B cells. (PMID:12591904)
• plasma stromal cell-derived factor-1 levels in normal healthy donors for allogeneic peripheral blood stem cell transplantation (PBSCT) and in patients for autologous PBSCT (PMID:12692604)
• Stromal cell-derived factor 1alpha stimulates human glioblastoma cell growth through the activation of both extracellular signal-regulated kinases 1/2 and Akt. (PMID:12702590)
• Sdf1 is expressed in myocardium and skeletal muscle. (PMID:12705474)
• invading extravillous trophoblasts that eventually perform endovascular invasion express CXCL12, the ligand for CXCR4, but not ligands for CXCR3. (PMID:12730110)
• SDF-1 enhanced the expansion and differentiation of primitive cord blood cells in a manner that was dependent upon both the concentration of SDF-1 and the presence of specific cytokines (PMID:12750733)
• examination of expression in prostate cancer (PMID:12761880)
• SDF-1-dependent polarization of CXCR4 is promoted by leukocyte-endothelium interaction (PMID:12766157)
• SDF-1 activated MMP-9 in bone marrow (BM) cells, causing release of soluble Kit-ligand and transfer of hematopoietic stem cells from a quiescent to a proliferative niche (PMID:12769333)
• TGF-beta1-controlled reduction in SDF-1 expression influences bone marrow cell migration and adhesion, which could affect the motility of cells trafficking the bone marrow. (PMID:12775566)
• Factors other than alteration in SDF-1/CXCR4 chemokine system must account for marrow infiltration of neoplastic cells in B-cell chronic lymphocytic leukemia. (PMID:12783211)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cxcl12a	ENSDARG00000037116
danio_rerio	cxcl12b	ENSDARG00000055100
mus_musculus	Cxcl12	ENSMUSG00000061353
rattus_norvegicus	Cxcl12	ENSRNOG00000013589

Protein

Protein identifiers

Stromal cell-derived factor 1 — P48061 (reviewed: P48061)

Alternative names: C-X-C motif chemokine 12, Intercrine reduced in hepatomas, Pre-B cell growth-stimulating factor

All UniProt accessions (1): P48061

UniProt curated annotations — full annotation on UniProt →

Function. Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for CXCL12/SDF-1. Binds to the allosteric site (site 2) of integrins and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 in a CXCR4-independent manner. Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and ACKR3, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. Inhibits CXCR4-mediated infection by T-cell line-adapted HIV-1. Plays a protective role after myocardial infarction. Induces down-regulation and internalization of ACKR3 expressed in various cells. Has several critical functions during embryonic development; required for B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation. Stimulates the proliferation of bone marrow-derived B-cell progenitors in the presence of IL7 as well as growth of stromal cell-dependent pre-B-cells. Shows a reduced chemotactic activity. Shows a reduced chemotactic activity. Binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3-67) and thus to preserve activity on local sites.

Subunit / interactions. Monomer or homodimer; in equilibrium. Dimer formation is induced by non acidic pH and the presence of multivalent anions, and by binding to CXCR4 or heparin. Monomeric form is required for full chemotactic activity and resistance to ischemia/reperfusion injury, whereas the dimeric form acts as a partial agonist of CXCR4, stimulating Ca2+ mobilization but with no chemotactic activity and instead acts as a selective antagonist that blocks chemotaxis induced by the monomeric form. Interacts with the N-terminus of ACKR3. Interacts with integrin subunit ITGB3 (via the allosteric site (site 2)). Interacts with TNFAIP6 (via Link domain). (Microbial infection) Interacts with molluscum contagiosum virus protein MC148.

Subcellular location. Secreted.

Tissue specificity. Isoform Alpha and isoform Beta are ubiquitously expressed, with highest levels detected in liver, pancreas and spleen. Isoform Gamma is mainly expressed in heart, with weak expression detected in several other tissues. Isoform Delta, isoform Epsilon and isoform Theta have highest expression levels in pancreas, with lower levels detected in heart, kidney, liver and spleen.

Post-translational modifications. Processed forms SDF-1-beta(3-72) and SDF-1-alpha(3-67) are produced after secretion by proteolytic cleavage of isoforms Beta and Alpha, respectively. The N-terminal processing is probably achieved by DPP4. Isoform Alpha is first cleaved at the C-terminus to yield a SDF-1-alpha(1-67) intermediate before being processed at the N-terminus. The C-terminal processing of isoform Alpha is reduced by binding to heparin and, probably, cell surface proteoglycans.

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

Isoforms (7)

UniProt ID	Names	Canonical?
P48061-1	Beta, SDF-1-beta(1-72), hSDF-1beta	yes
P48061-2	Alpha, SDF-1-alpha(1-68), hSDF-1alpha
P48061-3	Gamma, hSDF-1gamma, SDF-1g
P48061-4	Delta, hSDF-1delta
P48061-5	Epsilon, hSDFepsilon
P48061-6	Theta, hSDFphi, hSDFtheta, Phi
P48061-7	7

RefSeq proteins (5): NP_000600, NP_001029058, NP_001171605, NP_001264919, NP_954637* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00048

UniProt features (79 total): mutagenesis site 47, splice variant 6, strand 6, site 4, binding site 4, chain 3, helix 3, disulfide bond 2, turn 2, signal peptide 1, short sequence motif 1

Structure

Experimental structures (PDB)

34 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3GV3	X-RAY DIFFRACTION	1.6
6SHR	X-RAY DIFFRACTION	1.75
4UAI	X-RAY DIFFRACTION	1.9
2J7Z	X-RAY DIFFRACTION	1.95
1QG7	X-RAY DIFFRACTION	2
2NWG	X-RAY DIFFRACTION	2.07
1A15	X-RAY DIFFRACTION	2.2
3HP3	X-RAY DIFFRACTION	2.2
9UPV	ELECTRON MICROSCOPY	2.7
4LMQ	X-RAY DIFFRACTION	2.77
9UPU	ELECTRON MICROSCOPY	2.8
8K3Z	ELECTRON MICROSCOPY	2.81
8U4O	ELECTRON MICROSCOPY	3.29
7SK4	ELECTRON MICROSCOPY	3.3
7SK7	ELECTRON MICROSCOPY	3.3
7SK8	ELECTRON MICROSCOPY	3.3
9ME1	ELECTRON MICROSCOPY	3.37
9E82	ELECTRON MICROSCOPY	3.4
9MEU	ELECTRON MICROSCOPY	3.46
7SK3	ELECTRON MICROSCOPY	3.8
7SK5	ELECTRON MICROSCOPY	4
7SK6	ELECTRON MICROSCOPY	4
1SDF	SOLUTION NMR
1VMC	SOLUTION NMR
2K01	SOLUTION NMR
2K03	SOLUTION NMR
2K04	SOLUTION NMR
2K05	SOLUTION NMR
2KEC	SOLUTION NMR
2KED	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48061-F1	83.85	0.34

Antibody-complex structures (SAbDab): 9 — 4LMQ, 7SK3, 7SK4, 7SK5, 7SK6, 7SK7, 7SK8, 8K3Z, 9E82

Functional residue map

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

Catalytic / active sites (4): 46 (important for dimer formation); 48 (important for integrin interaction and activation); 64 (important for integrin interaction and activation); 45 (important for integrin interaction and activation)

Ligand- & substrate-binding residues (4): 41–51; 62; 69; 85

Disulfide bonds (2): 30–55, 32–71

Mutagenesis-validated functional residues (47):

Position	Phenotype
22–23	abolished cxcr4 activation ability, but only slightly impaired binding to the receptor.
22	loss of chemotactic activity.
22	abolished cxcr4 activation ability, but only slightly impaired binding to the receptor.
23	abolished cxcr4 activation ability, but only slightly impaired binding to the receptor.
25–27	significantly impaired cxcr4 activation ability, but only slightly impaired binding to the receptor.
28	impaired cxcr4 activation ability, but only slightly impaired binding to the receptor.
28	no significant effect on cxcr4 binding or activation.
29	slightly impaired binding and activation of cxcr4.
29	greatly impaired chemotactic activity and enhanced inhibition by heparin.
33–38	significantly decreased chemotactic activity.
33	significantly decreased anti-hiv-1 and chemotactic activities.
33	slightly impaired chemotactic activity and enhanced inhibition by heparin. greatly impaired chemotactic activity; when a
34	no effect on anti-hiv-1 and chemotactic activities. slightly impaired chemotactic activity and no effect on inhibition b
35	no effect on anti-hiv-1 and chemotactic activities. slightly impaired chemotactic activity and no effect on inhibition b
36–38	slightly impaired chemotactic activity, no effect on inhibition by heparin.
36	no effect on anti-hiv-1 and chemotactic activities.
37	no effect on anti-hiv-1 and chemotactic activities.
38	no effect on anti-hiv-1 and chemotactic activities.
41	no effect on cxcr4 activation.
45–48	loss of heparin-binding capacity.
45	loss of integrin activation; when associated with e-48 or e-64.
45	55-fold reduction in binding affinity for link domain of tnfaip6; when associated with s-46 and s-48.
46	reduced dimerization in neutral ph. eliminates the ph dependence of dimerization.
46	no significant effect on dimerization in neutral ph. eliminates the ph dependence of dimerization.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-1251985	Nuclear signaling by ERBB4
R-HSA-376176	Signaling by ROBO receptors
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-418594	G alpha (i) signalling events
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-1236394	Signaling by ERBB4
R-HSA-1266738	Developmental Biology
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-422475	Axon guidance
R-HSA-500792	GPCR ligand binding
R-HSA-8939211	ESR-mediated signaling
R-HSA-9006931	Signaling by Nuclear Receptors
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9675108	Nervous system development

MSigDB gene sets: 613 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, ELVIDGE_HYPOXIA_DN, MODULE_92, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_BEHAVIOR, MCLACHLAN_DENTAL_CARIES_UP, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CELL_CHEMOTAXIS, GOBP_RESPONSE_TO_PEPTIDE

GO Biological Process (46): response to hypoxia (GO:0001666), neuron migration (GO:0001764), positive regulation of endothelial cell proliferation (GO:0001938), intracellular calcium ion homeostasis (GO:0006874), chemotaxis (GO:0006935), defense response (GO:0006952), immune response (GO:0006955), cell adhesion (GO:0007155), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), axon guidance (GO:0007411), blood circulation (GO:0008015), regulation of actin polymerization or depolymerization (GO:0008064), adult locomotory behavior (GO:0008344), response to virus (GO:0009615), telencephalon cell migration (GO:0022029), positive regulation of cell migration (GO:0030335), animal organ regeneration (GO:0031100), positive regulation of dopamine secretion (GO:0033603), integrin activation (GO:0033622), chemokine (C-X-C motif) ligand 12 signaling pathway (GO:0038146), CXCL12-activated CXCR4 signaling pathway (GO:0038160), response to peptide hormone (GO:0043434), positive regulation of neuron differentiation (GO:0045666), positive regulation of cell adhesion (GO:0045785), positive regulation of axon extension involved in axon guidance (GO:0048842), induction of positive chemotaxis (GO:0050930), detection of temperature stimulus involved in sensory perception of pain (GO:0050965), detection of mechanical stimulus involved in sensory perception of pain (GO:0050966), cell chemotaxis (GO:0060326), chemokine-mediated signaling pathway (GO:0070098), positive regulation of monocyte chemotaxis (GO:0090026), positive regulation of calcium ion import (GO:0090280), negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage (GO:1902230), negative regulation of leukocyte tethering or rolling (GO:1903237), positive regulation of vasculature development (GO:1904018), response to ultrasound (GO:1990478), cellular response to chemokine (GO:1990869), positive regulation of T cell migration (GO:2000406), negative regulation of dendritic cell apoptotic process (GO:2000669)

GO Molecular Function (8): signaling receptor binding (GO:0005102), integrin binding (GO:0005178), chemokine activity (GO:0008009), growth factor activity (GO:0008083), chemokine receptor binding (GO:0042379), CXCR chemokine receptor binding (GO:0045236), cytokine activity (GO:0005125), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), external side of plasma membrane (GO:0009897), membrane (GO:0016020), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Signal Transduction	3
Signaling by GPCR	2
Signaling by ERBB4	1
Axon guidance	1
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
ESR-mediated signaling	1
Signaling by Receptor Tyrosine Kinases	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Nervous system development	1
Signaling by Nuclear Receptors	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to stress	2
cell migration	2
cellular process	2
chemokine receptor binding	2
receptor ligand activity	2
cellular anatomical structure	2
response to decreased oxygen levels	1
generation of neurons	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
response to chemical	1
taxis	1
immune system process	1
response to stimulus	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
axonogenesis	1
neuron projection guidance	1
circulatory system process	1
actin polymerization or depolymerization	1
regulation of actin filament length	1
regulation of actin filament organization	1
locomotory behavior	1
adult behavior	1
response to other organism	1
telencephalon development	1
forebrain cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
regeneration	1
animal organ development	1
dopamine secretion	1
regulation of dopamine secretion	1

Protein interactions and networks

STRING

4796 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CXCL12	CXCR4	P30991	999
CXCL12	CCR7	P32248	997
CXCL12	ACKR3	P25106	997
CXCL12	CXCR5	P32302	997
CXCL12	CCR2	P41597	997
CXCL12	CXCR2	P25025	996
CXCL12	CXCR3	P49682	996
CXCL12	CCR5	P51681	994
CXCL12	CXCR1	P25024	979
CXCL12	HMGB1	P09429	979
CXCL12	CX3CR1	P49238	974
CXCL12	KIT	P10721	972
CXCL12	CCL21	O00585	971
CXCL12	CD44	P16070	961
CXCL12	PF4	P02776	960

IntAct

58 interactions, top by confidence:

A	B	Type	Score
CXCL12	CCL5	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL12	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CCL5	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CCL11	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CCL13	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CCL20	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CCL21	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CCL25	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CCL26	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CCL28	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
XCL1	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
XCL2	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL2	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
PF4	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
PF4V1	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL6	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL9	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL10	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL11	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL14	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL17	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL12	CCL25	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL12	XCL1	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL12	XCL2	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL12	PF4V1	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL12	CXCL6	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL12	CXCL11	psi-mi:“MI:0407”(direct interaction)	0.560

BioGRID (38): CXCL12 (Biochemical Activity), CXCL12 (Affinity Capture-Western), CXCL12 (Affinity Capture-Western), CXCL12 (Affinity Capture-Western), CXCL12 (Reconstituted Complex), PDIA6 (Proximity Label-MS), CXCL12 (Co-crystal Structure), CXCL12 (Reconstituted Complex), CXCL12 (Reconstituted Complex), CXCL12 (Reconstituted Complex), CXCL12 (Reconstituted Complex), CXCL12 (Reconstituted Complex), CXCL12 (Reconstituted Complex), CXCL12 (Reconstituted Complex), CXCL12 (Reconstituted Complex)

ESM2 similar proteins: A5D7H1, A8MXK1, O76036, P01134, P01135, P08887, P14745, P35790, P48030, P48061, P55244, P98135, Q01134, Q05078, Q06922, Q08334, Q08DW9, Q08E08, Q0V881, Q12841, Q28284, Q29423, Q2KI11, Q3SXP7, Q3UHH2, Q58D84, Q5M7U7, Q5R9Y1, Q5SQ64, Q62356, Q62632, Q6AZB0, Q6MG56, Q6UXG2, Q7M729, Q7M730, Q7TPB4, Q86XW9, Q8BHK2, Q8BZI6

Diamond homologs: O62657, O97919, P08317, P10145, P30882, P40224, P41324, P48061, P49113, P50231, P67813, P67814, P97272, Q5EBF6, Q8HYQ1, Q8UUJ9, Q91ZL1, Q9XSX5, A9QWP9, O43927, O55235, O62812, P02775, P09340, P09341, P10889, P12850, P14095, P18340, P19874, P19875, P19876, P22952, P26894, P30348, P30782, P36925, P42830, P46653, P50228

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
CXCL12	up-regulates	CXCR4	binding
CXCL12	up-regulates	ACKR3	binding
CXCL12	up-regulates	Angiogenesis
SNAI2	“up-regulates quantity by expression”	CXCL12	“transcriptional regulation”
hsa-miR-1-5p	“down-regulates quantity by repression”	CXCL12	“post transcriptional regulation”
hsa-miR-101-5p	“down-regulates quantity by repression”	CXCL12	“post transcriptional regulation”
hsa-mir-126-5p	“down-regulates quantity by repression”	CXCL12	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 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	16	149.8×	8e-33
Class A/1 (Rhodopsin-like receptors)	7	25.9×	4e-08
Peptide ligand-binding receptors	7	25.9×	4e-08
G alpha (i) signalling events	13	25.3×	2e-15
GPCR ligand binding	7	22.5×	9e-08
Signaling by GPCR	7	14.0×	2e-06
GPCR downstream signalling	6	13.0×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
eosinophil chemotaxis	6	183.2×	1e-11
chemokine-mediated signaling pathway	13	175.5×	3e-25
neutrophil chemotaxis	9	107.1×	3e-15
antimicrobial humoral immune response mediated by antimicrobial peptide	14	94.5×	1e-23
chemotaxis	13	73.6×	2e-20
cell chemotaxis	8	61.7×	1e-11
cell-cell signaling	12	34.8×	6e-15
cellular response to lipopolysaccharide	7	28.6×	8e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	6
Benign	24

Top pathogenic / likely-pathogenic (0)

SpliceAI

728 predictions. Top by Δscore:

Variant	Effect	Δscore
10:44378635:A:AC	donor_gain	1.0000
10:44378636:C:CC	donor_gain	1.0000
10:44378724:C:CC	acceptor_gain	1.0000
10:44378726:G:C	acceptor_gain	1.0000
10:44380761:A:AC	donor_gain	1.0000
10:44380762:C:CC	donor_gain	1.0000
10:44380762:CA:C	donor_gain	1.0000
10:44384941:TTA:T	donor_loss	1.0000
10:44384942:TACCG:T	donor_loss	1.0000
10:44384943:A:AC	donor_gain	1.0000
10:44384944:C:CC	donor_gain	1.0000
10:44384944:CCGT:C	donor_gain	1.0000
10:44378631:GCTT:G	donor_loss	0.9900
10:44378632:CTT:C	donor_loss	0.9900
10:44378633:TT:T	donor_loss	0.9900
10:44378634:TACTT:T	donor_loss	0.9900
10:44378635:ACTT:A	donor_loss	0.9900
10:44378719:GGGCT:G	acceptor_gain	0.9900
10:44378720:GGCT:G	acceptor_gain	0.9900
10:44378721:GCT:G	acceptor_gain	0.9900
10:44378722:CT:C	acceptor_gain	0.9900
10:44378722:CTCTG:C	acceptor_gain	0.9900
10:44378723:TCTGT:T	acceptor_gain	0.9900
10:44378724:C:A	acceptor_loss	0.9900
10:44378724:C:G	acceptor_gain	0.9900
10:44378726:G:GC	acceptor_gain	0.9900
10:44380762:CACA:C	donor_gain	0.9900
10:44384939:ACTT:A	donor_loss	0.9900
10:44384943:AC:A	donor_gain	0.9900
10:44384943:ACCGT:A	donor_gain	0.9900

AlphaMissense

579 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:44378669:C:A	W78C	0.999
10:44378669:C:G	W78C	0.999
10:44378671:A:G	W78R	0.999
10:44378671:A:T	W78R	0.999
10:44378691:C:G	C71S	0.999
10:44378692:A:G	C71R	0.999
10:44378692:A:T	C71S	0.999
10:44378688:A:T	I72N	0.998
10:44378690:G:C	C71W	0.998
10:44378691:C:T	C71Y	0.998
10:44378721:G:T	A61D	0.998
10:44380766:A:T	I59N	0.998
10:44380778:C:G	C55S	0.998
10:44380779:A:T	C55S	0.998
10:44380811:A:T	V44D	0.998
10:44380854:A:G	C30R	0.998
10:44380777:A:C	C55W	0.997
10:44380778:C:T	C55Y	0.997
10:44380779:A:G	C55R	0.997
10:44380802:A:T	L47H	0.997
10:44380847:C:G	C32S	0.997
10:44380847:C:T	C32Y	0.997
10:44380848:A:G	C32R	0.997
10:44380848:A:T	C32S	0.997
10:44380853:C:G	C30S	0.997
10:44380854:A:T	C30S	0.997
10:44380766:A:C	I59S	0.996
10:44380778:C:A	C55F	0.996
10:44380802:A:G	L47P	0.996
10:44380846:G:C	C32W	0.996

dbSNP variants (sampled 300 via entrez): RS1000034232 (10:44370665 G>A), RS1000187218 (10:44373763 C>T), RS1000200160 (10:44374120 G>A,T), RS1000251129 (10:44374724 G>T), RS1000303747 (10:44380319 T>C), RS1000458577 (10:44385235 C>T), RS1000476238 (10:44378944 C>T), RS1000524471 (10:44375155 C>A,T), RS1000535782 (10:44375369 G>A,C), RS1000800716 (10:44379956 GAA>G), RS1000844711 (10:44384277 C>T), RS1001228934 (10:44385169 C>G), RS1001968466 (10:44379560 A>T), RS1002078814 (10:44374614 CGAG>C), RS1002088562 (10:44374355 G>A,T)

Disease associations

OMIM: gene MIM:600835 | disease phenotypes: MIM:609423

GenCC curated gene-disease

Mondo (1): susceptibility to HIV infection (MONDO:0004951)

Orphanet (0):

HPO phenotypes

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

GWAS associations

40 associations (top):

Study	Trait	p-value
GCST000057_5	Coronary heart disease	9.000000e-08
GCST000340_2	Myocardial infarction (early onset)	7.000000e-09
GCST000998_17	Coronary heart disease	3.000000e-10
GCST001757_4	Schizophrenia	3.000000e-06
GCST002289_11	Coronary artery disease	2.000000e-06
GCST002363_4	Response to anti-retroviral therapy (ddI/d4T) in HIV-1 infection (Grade 3 peripheral neuropathy)	8.000000e-09
GCST002805_3	Body mass index	6.000000e-06
GCST003069_4	Left superior temporal gyrus thickness (schizophrenia interaction)	2.000000e-06
GCST003116_19	Coronary artery disease	6.000000e-15
GCST003117_14	Myocardial infarction	8.000000e-11
GCST003470_9	Coronary artery disease	2.000000e-09
GCST004610_110	White blood cell count	5.000000e-13
GCST004613_16	Sum neutrophil eosinophil counts	1.000000e-09
GCST004614_37	Granulocyte count	8.000000e-10
GCST004620_115	Sum basophil neutrophil counts	4.000000e-09
GCST004625_178	Monocyte count	6.000000e-11
GCST004626_78	Myeloid white cell count	2.000000e-10
GCST004629_89	Neutrophil count	6.000000e-09
GCST004642_1	QT interval (ambient particulate matter interaction)	2.000000e-08
GCST004689_2	Resistance to Mycobacterium tuberculosis in HIV-positive individuals measured by a negative tuberculin skin test (continuous)	6.000000e-06
GCST004787_21	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	6.000000e-13
GCST006585_639	Blood protein levels	1.000000e-06
GCST007094_33	Diastolic blood pressure	1.000000e-09
GCST007098_92	Diastolic blood pressure	5.000000e-08
GCST007098_93	Diastolic blood pressure	4.000000e-07
GCST009399_1	Smoking initiation (ever regular vs never regular)	2.000000e-08
GCST010479_14	Coronary artery disease	1.000000e-12
GCST010993_4	Anti-drug antibodies in autoimmune disease (time to event)	4.000000e-06
GCST011364_15	Myocardial infarction	4.000000e-10
GCST011365_43	Myocardial infarction	2.000000e-17

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0000180	HIV-1 infection
EFO:0005937	longitudinal BMI measurement
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0004682	QT interval
EFO:0008255	particulate matter air pollution measurement
EFO:0008307	tuberculin skin test reactivity measurement
EFO:0008322	decreased susceptibility to bacterial infection
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0010559	anti-drug antibody measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004587	lymphocyte count
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3286074 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 65,885 (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
CHEMBL18442	PLERIXAFOR	4	11,099
CHEMBL898	DIFLUNISAL	4	54,786

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1801157	Efficacy	3	alemtuzumab;chlorambucil;cyclophosphamide;fludarabine;prednisone;rituximab;vincristine	Leukemia;Lymphocytic;Chronic;B-Cell

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1801157	CXCL12	3	2.25	1	alemtuzumab;chlorambucil;cyclophosphamide;fludarabine;prednisone;rituximab;vincristine
rs3740085	CXCL12		0.00	0

ChEMBL bioactivities

37 potent at pChembl≥5 of 43 total, top 36 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.24	IC50	5.7	nM	PLERIXAFOR
7.60	Ki	25	nM	CHEMBL4170392
7.36	Ki	44	nM	CHEMBL4160309
7.32	Ki	48	nM	CHEMBL4160346
7.28	Ki	53	nM	CHEMBL126657
7.28	Ki	53	nM	CHEMBL4167574
7.15	Ki	71	nM	CHEMBL4175451
6.97	Ki	107	nM	CHEMBL4166275
6.97	Ki	107	nM	CHEMBL4168220
6.97	Ki	107	nM	CHEMBL4168923
6.97	Ki	107	nM	CHEMBL4169628
6.97	Ki	107	nM	CHEMBL4163005
6.80	Kd	160	nM	CHEMBL5563111
6.70	Kd	200	nM	CHEMBL113835
6.69	Ki	203	nM	CHEMBL4160583
6.57	Ki	267	nM	CHEMBL4166454
6.54	Ki	285	nM	CHEMBL4173832
6.46	Ki	350	nM	CHEMBL127593
6.45	Ki	357	nM	CHEMBL4170951
6.45	Ki	357	nM	CHEMBL4175213
6.45	Ki	357	nM	CHEMBL4162605
6.37	Ki	430	nM	CHEMBL4169688
6.32	Ki	475	nM	CHEMBL4159394
6.30	Ki	496	nM	CHEMBL4175047
6.22	IC50	608.2	nM	PLERIXAFOR
6.21	IC50	621.4	nM	CHEMBL5283078
6.20	Ki	625	nM	CHEMBL226710
6.15	Ki	714	nM	CHEMBL4164132
6.11	Kd	780	nM	CHEMBL4166454
6.10	Kd	800	nM	DIFLUNISAL
5.97	Ki	1070	nM	CHEMBL243400
5.97	Ki	1071	nM	CHEMBL4167307
5.86	Ki	1380	nM	CHEMBL4159676
5.78	Ki	1680	nM	CHEMBL4163644
5.75	Ki	1780	nM	CHEMBL130639
5.27	Ki	5350	nM	CHEMBL4177186

PubChem BioAssay actives

34 with measured affinity, of 162 total; 32 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
Plerixafor	2131642: Inhibition of CXCL12 (unknown origin) mediated chemotaxis	ic50	0.0057	uM
(E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-propan-2-ylphenyl)prop-2-en-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.0250	uM
(E)-1-(4-bromophenyl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.0440	uM
(E)-1-(2,4-dichlorophenyl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.0480	uM
(E)-1-(4-chlorophenyl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.0530	uM
(E)-1-(2,5-dichlorophenyl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.0530	uM
(E)-1-(2,6-dichlorophenyl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.0710	uM
(E)-1-(2-chlorophenyl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.1070	uM
(E)-1-(4-chloro-2-fluorophenyl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.1070	uM
(2E)-5-chloro-2-[(4-hydroxy-3-methoxyphenyl)methylidene]-3H-inden-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.1070	uM
4-[3-(4-chlorophenyl)-4,5-dihydro-1H-pyrazol-5-yl]-2-methoxyphenol	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.1070	uM
(E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-iodophenyl)prop-2-en-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.1070	uM
1-[1-[[5-chloro-2-[(3-cyanophenyl)methoxy]-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl]methyl]piperidine-2-carbonyl]-N-[[4-[[2-methoxy-4-[(E)-3-(4-methoxyphenyl)-3-oxoprop-1-enyl]phenoxy]methyl]phenyl]methyl]piperidine-4-carboxamide	2072215: Binding affinity to recombinant human CXCL12 expressed in Escherichia coli assessed as dissociation constant incubated for 0.5 hrs by SPR analysis	kd	0.1600	uM
(2Z)-6-chloro-2-[(4-hydroxy-3-methoxyphenyl)methylidene]-1-benzofuran-3-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.2030	uM
6-(4-chlorophenyl)-4-(4-hydroxy-3-methoxyphenyl)-1H-pyrimidin-2-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.2670	uM
(E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-methylphenyl)prop-2-en-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.2850	uM
(E)-1-(4-chlorophenyl)-3-(3,4-dihydroxyphenyl)prop-2-en-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.3500	uM
(E)-1-(2,3-dichlorophenyl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.3570	uM
(E)-3-[3-(2-aminoethoxy)-4-hydroxyphenyl]-1-(4-chlorophenyl)prop-2-en-1-one;hydrochloride	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.3570	uM
(3E)-7-chloro-3-[(4-hydroxy-3-methoxyphenyl)methylidene]chromen-4-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.3570	uM
(E)-1-(4-fluorophenyl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.4300	uM
(E)-3-[3-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]-4-hydroxyphenyl]-1-(4-chlorophenyl)prop-2-en-1-one;hydrochloride	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.4750	uM
(2E)-2-[[3-[2-(2-aminoethoxy)ethoxy]-4-hydroxyphenyl]methylidene]-5-chloro-3H-inden-1-one;hydrochloride	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.4960	uM
N’-cyclohexyl-N-[[4-[[3-(cyclohexylamino)propylamino]methyl]phenyl]methyl]propane-1,3-diamine	1927213: Inhibition of SDF-1 alpha induced cell migration in human SUP-T1 cells pre-incubated for 30 mins followed by SDF-1 alpha addition measured after 3 hrs by cell Titer-96 reagent based analysis	ic50	0.6214	uM
(E)-1-(4-chlorophenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.6250	uM
(E)-1-(3,4-dichlorophenyl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	0.7140	uM
(E)-3-(4-hydroxy-3-methoxyphenyl)-1-[4-(trifluoromethyl)phenyl]prop-2-en-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	1.0700	uM
(E)-3-[3-[2-(2-aminoethoxy)ethoxy]-4-hydroxyphenyl]-1-(4-chlorophenyl)prop-2-en-1-one;hydrochloride	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	1.0710	uM
(E)-1-(4-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)prop-2-en-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	1.3800	uM
4-[6-(4-chlorophenyl)-2-methylpyrimidin-4-yl]-2-methoxyphenol	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	1.6800	uM
(E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	1.7800	uM
4-[(E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoyl]benzoic acid	1357097: Binding affinity to Texas Red-labelled CXCL12 (unknown origin) assessed as inhibition of CXCL12-Texas Red binding to EGFP-labeled human CXCR4 expressed in HEK293 cell membranes pre-incubated for 1 hr by FRET-based binding assay	ki	5.3500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases reaction, increases expression, increases secretion, affects response to substance, affects cotreatment (+3 more)	24
Valproic Acid	decreases expression, increases methylation, affects cotreatment, increases expression, affects expression	9
bisphenol A	increases expression, decreases reaction, increases secretion, affects response to substance, affects reaction (+1 more)	8
Resveratrol	decreases reaction, increases secretion, affects cotreatment, increases expression, decreases expression (+1 more)	5
Fulvestrant	increases expression, increases secretion, decreases expression, decreases reaction	5
Tamoxifen	affects binding, increases reaction, affects cotreatment, increases expression, decreases expression (+2 more)	5
trichostatin A	affects cotreatment, increases expression	4
Coumestrol	affects cotreatment, increases expression, decreases reaction, affects reaction	4
Genistein	affects response to substance, increases secretion, decreases reaction, increases expression	4
Raloxifene Hydrochloride	decreases reaction, increases secretion, decreases expression, affects cotreatment, increases expression	4
plerixafor	decreases expression, affects localization, decreases reaction, increases phosphorylation	3
entinostat	increases expression, affects cotreatment	3
Calcium	increases uptake, affects localization, decreases reaction	3
Estrogens	decreases reaction, increases expression	3
Oxygen	increases expression, increases response to substance	3
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	3
daidzein	increases expression, decreases reaction	2
afimoxifene	decreases reaction, increases secretion, increases expression	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
hydroquinone	decreases secretion, decreases expression	2
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	2
belinostat	affects cotreatment, decreases expression, increases expression	2
Decitabine	increases expression, decreases methylation	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Glyphosate	decreases expression, increases reaction, increases expression	2
Cadmium	decreases expression, increases expression, increases secretion, affects reaction, affects binding (+1 more)	2
Ethinyl Estradiol	increases expression, increases secretion	2
Etoposide	decreases expression	2
Progesterone	affects cotreatment, decreases expression	2

ChEMBL screening assays

29 unique, capped per target: 29 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3293898	Binding	Binding affinity to human recombinant CXCL12 by surface plasmon resonance assay	Synthesis and biological evaluation of a unique heparin mimetic hexasaccharide for structure-activity relationship studies. — J Med Chem

Clinical trials (associated diseases)

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