CXCR4

Summary

CXCR4 (C-X-C motif chemokine receptor 4, HGNC:2561) is a protein-coding gene on chromosome 2q22.1, encoding C-X-C chemokine receptor type 4 (P61073). Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. In precision oncology, CXCR4 EXPRESSION is associated with resistance to Docetaxel in Gastric Adenocarcinoma (CIViC Level B); 1 further curated variant–drug associations are listed below.

This gene encodes a CXC chemokine receptor specific for stromal cell-derived factor-1. The protein has 7 transmembrane regions and is located on the cell surface. It acts with the CD4 protein to support HIV entry into cells and is also highly expressed in breast cancer cells. Mutations in this gene have been associated with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Source: NCBI Gene 7852 — RefSeq curated summary.

At a glance

• Gene–disease (curated): WHIM syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 16
• Clinical variants (ClinVar): 244 total — 30 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 40
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 4 cancer types
• MANE Select transcript: NM_003467

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2561
Approved symbol	CXCR4
Name	C-X-C motif chemokine receptor 4
Location	2q22.1
Locus type	gene with protein product
Status	Approved
Aliases	LESTR, NPY3R, HM89, NPYY3R, D2S201E, fusin, HSY3RR, NPYR, CD184
Ensembl gene	ENSG00000121966
Ensembl biotype	protein_coding
OMIM	162643
Entrez	7852

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000241393, ENST00000409817, ENST00000466288, ENST00000696136, ENST00000696137, ENST00000696152, ENST00000696228

RefSeq mRNA: 5 — MANE Select: NM_003467 NM_001008540, NM_001348056, NM_001348059, NM_001348060, NM_003467

CCDS: CCDS33295, CCDS46420, CCDS92871

Canonical transcript exons

ENST00000241393 — 2 exons

Exon	Start	End
ENSE00000827142	136114349	136115912
ENSE00003966218	136118046	136118149

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 99.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 171.4217 / max 19875.7685, expressed in 1136 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30804	165.6587	1125
30793	1.2599	281
30795	0.8371	169
30790	0.7687	233
30796	0.6520	177
30794	0.5815	181
30788	0.5706	165
30792	0.2993	108
30787	0.2014	81
30791	0.1703	67

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow	UBERON:0002371	99.62	gold quality
thymus	UBERON:0002370	99.49	gold quality
lymph node	UBERON:0000029	99.43	gold quality
epithelium of nasopharynx	UBERON:0001951	99.43	gold quality
nasopharynx	UBERON:0001728	99.41	gold quality
bone marrow cell	CL:0002092	99.37	gold quality
vermiform appendix	UBERON:0001154	99.37	gold quality
blood	UBERON:0000178	99.17	gold quality
spleen	UBERON:0002106	99.12	gold quality
visceral pleura	UBERON:0002401	99.08	gold quality
trabecular bone tissue	UBERON:0002483	99.07	gold quality
caecum	UBERON:0001153	98.48	gold quality
bone element	UBERON:0001474	98.35	gold quality
granulocyte	CL:0000094	98.26	gold quality
pericardium	UBERON:0002407	97.84	gold quality
gall bladder	UBERON:0002110	97.69	gold quality
olfactory bulb	UBERON:0002264	97.35	gold quality
pleura	UBERON:0000977	97.17	gold quality
buccal mucosa cell	CL:0002336	96.96	gold quality
leukocyte	CL:0000738	96.94	gold quality
palpebral conjunctiva	UBERON:0001812	96.87	gold quality
mononuclear cell	CL:0000842	96.76	gold quality
monocyte	CL:0000576	96.68	gold quality
cardia of stomach	UBERON:0001162	96.39	gold quality
mucosa of urinary bladder	UBERON:0001259	96.37	gold quality
right lung	UBERON:0002167	96.34	gold quality
lower lobe of lung	UBERON:0008949	96.15	gold quality
parietal pleura	UBERON:0002400	95.91	gold quality
ventricular zone	UBERON:0003053	95.86	gold quality
eye	UBERON:0000970	95.81	gold quality

Single-cell (SCXA)

Detected in 53 experiment(s), a significant marker in 45.

Experiment	Marker?	Max mean expression
E-CURD-97	yes	11321.74
E-MTAB-6678	yes	7919.04
E-MTAB-9467	yes	6257.69
E-CURD-79	yes	4988.32
E-CURD-46	yes	4820.19
E-MTAB-6701	yes	4718.18
E-CURD-126	yes	4488.09
E-HCAD-1	yes	3787.94
E-MTAB-10596	yes	3572.70
E-MTAB-10553	yes	3527.48
E-MTAB-6308	yes	3393.79
E-MTAB-8381	yes	3331.91
E-MTAB-10885	yes	3208.01
E-GEOD-135922	yes	3075.20
E-MTAB-8410	yes	3038.97

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ASCL2, BCL6, CEBPB, CREB1, CREB3, DNMT1, DNMT3B, ERG, ESR1, ETS1, ETV4, ETV5, FOXA2, FOXC1, FOXC2, FOXH1, FOXO1, FOXO3, GFI1, GLI1, HDAC3, HIF1A, IRF2, ITGAX, JUN, KLF2, KLF5, LEF1, MAX, MIXL1, MXD1, MYB, MYC, NANOG, NCOA2, NFKB1, NFKB, NRF1, PAX3

miRNA regulators (miRDB)

79 targeting CXCR4, 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-190A-3P	100.00	80.35	5520
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698

Literature-anchored findings (GeneRIF, showing 40)

• Biological characterization and chemokine receptor usage of HIV type 1 isolates prevalent in Brazil. (PMID:11559423)
• elastase-mediated proteolysis of SDF-1/CXCR4 is part of a mechanism regulating their biological functions in both homeostatic and pathologic processes (PMID:11867624)
• CCR-5 expression in thymocytes was significantly lower than that of CXCR-4 and there was no functional response. A modest increase in expression was associated with in vitro thymocyte stimulation. (PMID:11876757)
• the role of CD4, CXCR4, and CCR5 in HIV envelope-mediated apoptosis was examined in peripheral blood mononuclear cells (PMID:11878912)
• mechanism of ligand recognition (PMID:11880384)
• Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone. (PMID:11912162)
• Lipopolysaccharide, lipoarabinomannan and lipoteichoic acid down-regulated the expression of CXCR4 and CCR5 on monocytes (PMID:11920324)
• SDF-1/CXCR-4 identifies VEGF- and bFGF-regulated autocrine signaling systems that are essential regulators of endothelial cell morphogenesis and angiogenesis. (PMID:11929756)
• Membrane cholesterol is essential for CXCR4 conformation and binding to SDF-1 alpha on T cells and is required by HIV on target cell membranes for infection. (PMID:11937572)
• CXCR4/CXCL12 expression and signalling in kidney cancer (PMID:11953881)
• without functional CXCR4, morphogenesis of the hippocampal DG fails. (PMID:11983855)
• CXCR4 is present on the resident testicular macrophages in the interstitial space but not in the germ cell line (PMID:11994538)
• 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 of post-translational modifications of amino terminus in stromal-derived factor 1 alpha association and HIV-1 entry (PMID:12034737)
• HIV-1 crosses M cell monolayers and infects underlying CD4(+) target cells. Transport requires both lactosyl cerebroside and CXCR4 receptors. (PMID:12093918)
• CXCR4 expression is regulated by IL-6 or factors positively coupled to cAMP and results in SDF-1-dependent chemotaxis in central nervous system astrocytes (PMID:12171912)
• Follicular dendritic cell-mediated up-regulation of CXCR4 expression on CD4 T cells in coculture correlates with augmented HIV-1 binding and entry into these cells and increases susceptibility of germinal center CD4 T cells to HIV infection. (PMID:12193696)
• Crosstalk between BCR/ABL oncoprotein and CXCR4 signaling through a Src family kinase in human leukemia cells. (PMID:12208881)
• Protein-disulfide isomerase-mediated reduction of two disulfide bonds of HIV envelope glycoprotein 120 occurs post-binding to this protein and is required for fusion (PMID:12218052)
• CCR5-binding chemokines modulate CXCL12 (SDF-1)-induced responses of progenitor B cells in human bone marrow through heterologous desensitization of the chemokine receptor. (PMID:12239139)
• signaling is active in rhabdomyosarcoma cells and regulates locomotion, chemotaxis, and adhesion (PMID:12239174)
• results suggest dynamic CXCR4 expression on CD34(+) stem and progenitor cells, regulating their motility and repopulation capacities (PMID:12351385)
• P. falciparum antigens (PF-Ags) variably regulate the expression of HIV-1 coreceptors and modulate the infectability of CD4 cells by HIV-1 (PMID:12355376)
• Significant increase in surface CCR5 in CD4+, CD8+, CD19+ and CD14+ cells as well as an increased percentage of CXCR3 and CXCR4 in CD14+ cells in MS patients. (PMID:12356205)
• coreceptor binding domain, the V3 region of the surface envelope (SU) glycoprotein, was replaced by the V3 loop of a CD4- and CXCR4-tropic HIV-1 strain; the resulting virus, termed SIVagm3-X4mc, exclusively used CD4 and CXCR4 for cell entry (PMID:12368305)
• the importance of the V3 loop and the beta19 strand of an X4 gp120 glycoprotein in binding CXCR4 (PMID:12368322)
• CXCR4 signaling is mediated by beta-arrestin 2 (PMID:12370187)
• glioma cells express CXCR4, which functions to regulate survival in part through activating pathways such as Akt (PMID:12388552)
• Role of the intracellular domains of CXCR4 in SDF-1-mediated signaling (PMID:12393663)
• CXCR4 and motor protein nonmuscle myosin heavy chain-IIA colocalize at the leading edge of migrating T lymphocytes, together with filamentous actin and myosin light chain. (PMID:12421915)
• ligand-independent dimerization of this principal HIV-1 coreceptor (PMID:12433920)
• expressed in human brain tumors and is involved in glial proliferation in vitro (PMID:12485835)
• ubiquitination may contribute to finding of multiple MW isoforms of CXCR4 (PMID:12488503)
• Vascular endothelial growth factor promotes breast carcinoma invasion in an autocrine manner by regulating the chemokine receptor CXCR4. (PMID:12499259)
• CD45 differentially regulates CXCR4-mediated chemotactic activity and MAPK activation by modulating the activities of focal adhesion components (PMID:12519755)
• findings suggest that a subset of anaplastic thyroid carcinoma cells expresses functional CXCR4, which may be important in tumor cell migration and local tumor invasion (PMID:12519884)
• In the absence of any stimulation, human fetal astrocytes express mRNA for receptor CXCR4. (PMID:12555203)
• HIV-1 infection of neuronal cells may involve CCR5/CXCR4 receptor (PMID:12586555)
• L-selectin mobilized intracellular CXCR4 to significantly increase surface CXCR4 stimulation, inhibited SDF-1 induced CXCR4 internalization, increased SDF-1-induced lymphocyte adhesion and transendothelial migration. (PMID:12609846)
• some HIV-1 subtype C viruses, isolated from 29 South African patients with advanced AIDS, are able to use CCR5, CXCR4, or both CXCR4 and CCR5 for entry (PMID:12634405)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cxcr4b	ENSDARG00000041959
danio_rerio	cxcr4a	ENSDARG00000057633
mus_musculus	Cxcr4	ENSMUSG00000045382
rattus_norvegicus	Cxcr4	ENSRNOG00000003866

Paralogs (23): CCR6 (ENSG00000112486), CCRL2 (ENSG00000121797), CCR2 (ENSG00000121807), CCR7 (ENSG00000126353), ACKR4 (ENSG00000129048), ACKR3 (ENSG00000144476), ACKR2 (ENSG00000144648), RGR (ENSG00000148604), CXCR5 (ENSG00000160683), CCR5 (ENSG00000160791), CXCR1 (ENSG00000163464), CCR1 (ENSG00000163823), CX3CR1 (ENSG00000168329), CXCR6 (ENSG00000172215), XCR1 (ENSG00000173578), CCR9 (ENSG00000173585), CCR8 (ENSG00000179934), CXCR2 (ENSG00000180871), GALR2 (ENSG00000182687), CCR3 (ENSG00000183625), CCR4 (ENSG00000183813), CCR10 (ENSG00000184451), CXCR3 (ENSG00000186810)

Protein

Protein identifiers

C-X-C chemokine receptor type 4 — P61073 (reviewed: P61073)

Alternative names: FB22, Fusin, HM89, LCR1, Leukocyte-derived seven transmembrane domain receptor, Lipopolysaccharide-associated protein 3, NPYRL, Stromal cell-derived factor 1 receptor

All UniProt accessions (3): A0A8Q3WL10, A0A8Q3WLL1, P61073

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase. CXCR4 is coupled to G(i) G alpha proteins and mediates inhibition of adenylate cyclase. Involved in the AKT signaling cascade. Plays a role in regulation of cell migration, e.g. during wound healing. Also acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels. Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes. Involved in hematopoiesis and in cardiac ventricular septum formation. Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in cerebellar development; in the CNS, could mediate hippocampal-neuron surviva. (Microbial infection) Acts as a coreceptor (CD4 being the primary receptor) for human immunodeficiency virus-1/HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. Promotes Env-mediated fusion of the virus.

Subunit / interactions. Monomer. Can form homodimers. Interacts with CD164. Interacts (when phosphorylated) with ARRB1; the interaction is associated with internalization of the receptor and short-term desensitization to the ligand. Interacts with ARRB2; the interaction is dependent on the C-terminal phosphorylation of CXCR4 and allows activation of MAPK1 and MAPK3. Interacts with ARR3; the interaction is dependent on the C-terminal phosphorylation of CXCR4 and modulates calcium mobilization. Interacts with RNF113A; the interaction, enhanced by CXCL12, promotes CXCR4 ubiquitination and subsequent degradation. Interacts (via the cytoplasmic C-terminal) with ITCH (via the WW domains I and II); the interaction, enhanced by CXCL12, promotes CXCR4 ubiquitination and leads to its degradation. Interacts with extracellular ubiquitin. Interacts with DBN1; this interaction is enhanced by antigenic stimulation. Following LPS binding, may form a complex with GDF5, HSP90AA1 and HSPA8. (Microbial infection) Interacts with HIV-1 surface protein gp120 and Tat. (Microbial infection) Interacts with HHV-8 protein ORF K4. (Microbial infection) May interact with human cytomegalovirus/HHV-5 protein UL78. (Microbial infection) Interacts with Staphylococcus aureus protein SSL10.

Subcellular location. Cell membrane. Cell junction. Early endosome. Late endosome. Lysosome.

Tissue specificity. Expressed in numerous tissues, such as peripheral blood leukocytes, spleen, thymus, spinal cord, heart, placenta, lung, liver, skeletal muscle, kidney, pancreas, cerebellum, cerebral cortex and medulla (in microglia as well as in astrocytes), brain microvascular, coronary artery and umbilical cord endothelial cells. Isoform 1 is predominant in all tissues tested.

Post-translational modifications. Phosphorylated on agonist stimulation. Phosphorylation of the P-X-P-P motif promotes association with beta-arrestin ARRB1, leading to receptor desensitization and negative regulation of G-protein coupled receptor signaling. Phosphorylation at Ser-324 and Ser-325 leads to recruitment of ITCH, ubiquitination and protein degradation. Ubiquitinated after ligand binding, leading to its degradation. Ubiquitinated by ITCH at the cell membrane on agonist stimulation. The ubiquitin-dependent mechanism, endosomal sorting complex required for transport (ESCRT), then targets CXCR4 for lysosomal degradation. This process is dependent also on prior Ser-/Thr-phosphorylation in the C-terminal of CXCR4. Also binding of ARRB1 to STAM negatively regulates CXCR4 sorting to lysosomes though modulating ubiquitination of SFR5S. Sulfation on Tyr-21 is required for efficient binding of CXCL12/SDF-1alpha and promotes its dimerization. Tyr-7 and Tyr-12 are sulfated in a sequential manner after Tyr-21 is almost fully sulfated, with the binding affinity for CXCL12/SDF-1alpha increasing with the number of sulfotyrosines present. Sulfotyrosines Tyr-7 and Tyr-12 occupy clefts on opposing CXCL12 subunits, thus bridging the CXCL12 dimer interface and promoting CXCL12 dimerization. O- and N-glycosylated. Asn-11 is the principal site of N-glycosylation. There appears to be very little or no glycosylation on Asn-176. N-glycosylation masks coreceptor function in both X4 and R5 laboratory-adapted and primary HIV-1 strains through inhibiting interaction with their Env glycoproteins. The O-glycosylation chondroitin sulfate attachment does not affect interaction with CXCL12/SDF-1alpha nor its coreceptor activity.

Disease relevance. WHIM syndrome 1 (WHIMS1) [MIM:193670] An autosomal dominant immunologic disease characterized by neutropenia, hypogammaglobulinemia and extensive human papillomavirus (HPV) infection. Despite the peripheral neutropenia, bone marrow aspirates from affected individuals contain abundant mature myeloid cells, a condition termed myelokathexis. The disease is caused by variants affecting the gene represented in this entry. CXCR4 mutations play a role in the pathogenesis of Waldenstroem macroglobulinemia (WM) and influence disease presentation and outcome, as well as response to therapy. WM is a B-cell lymphoma characterized by accumulation of malignant lymphoplasmacytic cells in the bone marrow, lymph nodes and spleen, and hypersecretion of monoclonal immunoglobulin M (IgM). Excess IgM production results in serum hyperviscosity, tissue infiltration, and autoimmune-related pathology.

Domain organisation. The amino-terminus is critical for ligand binding. Residues in all four extracellular regions contribute to HIV-1 coreceptor activity. The P-X-P-P motif is phosphorylated in response to ligand binding, promoting. association with beta-arrestin ARRB1.

Induction. (Microbial infection) May be down-regulated by Human cytomegalovirus/HHV-5. (Microbial infection) May be down-regulated by HIV-1 tat.

Miscellaneous. Plerixafor (AMD3100), an antagonist of CXCR4 activity, blocks HIV-1 entry, interaction with CXCL12 and subsequent CXCR4 signaling.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P61073-1	1	yes
P61073-2	2, CXCR4-LO

RefSeq proteins (5): NP_001008540, NP_001334985, NP_001334988, NP_001334989, NP_003458* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000355	Chemokine_rcpt	Family
IPR001277	CXCR4/ACKR2	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR022726	Chemokine_CXCR4_N_dom	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001, PF12109

UniProt features (130 total): mutagenesis site 46, modified residue 17, helix 15, topological domain 8, region of interest 8, transmembrane region 7, strand 5, turn 5, sequence variant 4, glycosylation site 3, sequence conflict 2, short sequence motif 2, site 2, disulfide bond 2, chain 1, compositionally biased region 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

33 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3ODU	X-RAY DIFFRACTION	2.5
9UPV	ELECTRON MICROSCOPY	2.7
8U4N	ELECTRON MICROSCOPY	2.72
9UPU	ELECTRON MICROSCOPY	2.8
8K3Z	ELECTRON MICROSCOPY	2.81
3OE0	X-RAY DIFFRACTION	2.9
9MDU	ELECTRON MICROSCOPY	2.9
8YU7	ELECTRON MICROSCOPY	3.01
8ZPL	ELECTRON MICROSCOPY	3.01
3OE8	X-RAY DIFFRACTION	3.1
3OE9	X-RAY DIFFRACTION	3.1
4RWS	X-RAY DIFFRACTION	3.1
8U4R	ELECTRON MICROSCOPY	3.1
8U4P	ELECTRON MICROSCOPY	3.15
3OE6	X-RAY DIFFRACTION	3.2
8ZPM	ELECTRON MICROSCOPY	3.2
22XC	ELECTRON MICROSCOPY	3.28
8U4O	ELECTRON MICROSCOPY	3.29
8ZPN	ELECTRON MICROSCOPY	3.31
8U4S	ELECTRON MICROSCOPY	3.35
8U4Q	ELECTRON MICROSCOPY	3.36
9ME1	ELECTRON MICROSCOPY	3.37
8U4T	ELECTRON MICROSCOPY	3.38
9MEU	ELECTRON MICROSCOPY	3.46
9MEN	ELECTRON MICROSCOPY	3.57
9MEJ	ELECTRON MICROSCOPY	3.99
8I0Q	ELECTRON MICROSCOPY	4.45
8GP3	ELECTRON MICROSCOPY	4.8
9MET	ELECTRON MICROSCOPY	5.65
2K03	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61073-F1	82.84	0.58

Antibody-complex structures (SAbDab): 8 — 8GP3, 8I0Q, 8K3Z, 8U4Q, 8U4R, 8U4S, 8U4T, 8ZPN

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 (2): 171 (chemokine binding); 288 (chemokine binding)

Post-translational modifications (18): 7, 12, 21, 319, 321, 324, 325, 330, 339, 341, 342, 344, 346, 347, 348, 351, 352, 331

Disulfide bonds (2): 28–274, 109–186

Glycosylation sites (3): 11, 18, 176

Mutagenesis-validated functional residues (46):

Position	Phenotype
325	enhanced binding to itch. enhanced binding to itch and greatly increased protein degradation; when associated with d-324
330	no effect on binding to itch.
331	loss of ubiquitination by rnf113a.
2–9	reduced cxcl12 binding. abolishes signaling.
4–20	reduced cxcl12 binding. impaired signaling. reduced coreceptor activity for hiv-1 isolates lai and ndk.
7	reduced coreceptor activity for hiv-1 isolates lai and ndk. greatly reduced coreceptor activity for hiv-1 isolates lai a
7	sulfate incorporation greatly reduced; when associated with f-12 and f-21. moderate reduction in sulfate incorporation;
8	no effect on sulfate incorporation; when associated with a-9 and a-13.
9	no effect on sulfate incorporation; when associated with a-8 and a-13.
10–20	reduced cxcl12 binding. no effect on signaling.
11	reduced molecular weight. enhanced coreceptor activity on r5 hiv-1 isolate envs. slight further enhancement of corecepto
12	greatly reduced coreceptor activity for hiv-1 isolates lai and ndk; when associated with a-7.
12	sulfate incorporation greatly reduced; when associated with f-7 and f-21. moderate reduction in sulfate incorporation; w
13	enhanced coreceptor activity on r5 hiv-1 isolate envs. no effect on sulfate incorporation; when associated with a-8 and
14–15	reduced cxcl12 binding. reduced coreceptor activity for hiv-1 isolate ndk.
18	sulfate incorporation greatly reduced; when associated with f-21. moderate reduction in sulfate incorporation; when asso
21	reduced cxcl12 binding. reduced coreceptor activity for hiv-1 isolates lai and ndk.
21	sulfate incorporation greatly reduced; when associated with f-7 and f-12. sulfate incorporation greatly reduced; when as
28	reduced signaling following cxcl12-binding.
97	reduced cxcl12 binding. abolishes signaling. markedly reduced coreceptor activity for hiv-1 isolate lai.
119	no reduction of agonist-induced g-protein activation.
119	loss of agonist-induced g-protein activation.
119	constitutive g-protein activation, with further activation induced by agonist.
125	increased thermostability.
133	no reduction of agonist-induced g-protein activation.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-173107	Binding and entry of HIV virion
R-HSA-376176	Signaling by ROBO receptors
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-418594	G alpha (i) signalling events
R-HSA-9823730	Formation of definitive endoderm
R-HSA-9827857	Specification of primordial germ cells
R-HSA-9937080	Developmental Lineage of Multipotent Pancreatic Progenitor Cells

MSigDB gene sets: 756 (showing top): TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, MODULE_52, HORIUCHI_WTAP_TARGETS_DN, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_DENDRITIC_CELL_MIGRATION, MCLACHLAN_DENTAL_CARIES_UP, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, XU_GH1_AUTOCRINE_TARGETS_UP, LFA1_Q6, MODULE_45, MODULE_64, AREB6_03, GOZGIT_ESR1_TARGETS_DN

GO Biological Process (29): response to hypoxia (GO:0001666), dendritic cell chemotaxis (GO:0002407), apoptotic process (GO:0006915), inflammatory response (GO:0006954), immune response (GO:0006955), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), positive regulation of cytosolic calcium ion concentration (GO:0007204), brain development (GO:0007420), response to virus (GO:0009615), calcium-mediated signaling (GO:0019722), neurogenesis (GO:0022008), regulation of cell adhesion (GO:0030155), positive regulation of cell migration (GO:0030335), CXCL12-activated CXCR4 signaling pathway (GO:0038160), myelin maintenance (GO:0043217), positive regulation of oligodendrocyte differentiation (GO:0048714), cell chemotaxis (GO:0060326), cellular response to cytokine stimulus (GO:0071345), positive regulation of cold-induced thermogenesis (GO:0120162), positive regulation of vasculature development (GO:1904018), positive regulation of macrophage migration inhibitory factor signaling pathway (GO:2000448), chemotaxis (GO:0006935), signal transduction (GO:0007165), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), cell migration (GO:0016477), regulation of cell migration (GO:0030334), symbiont entry into host cell (GO:0046718), chemokine-mediated signaling pathway (GO:0070098)

GO Molecular Function (14): virus receptor activity (GO:0001618), actin binding (GO:0003779), G protein-coupled receptor activity (GO:0004930), coreceptor activity (GO:0015026), C-C chemokine receptor activity (GO:0016493), C-X-C chemokine receptor activity (GO:0016494), C-C chemokine binding (GO:0019957), ubiquitin protein ligase binding (GO:0031625), myosin light chain binding (GO:0032027), C-X-C motif chemokine 12 receptor activity (GO:0038147), ubiquitin binding (GO:0043130), chemokine receptor activity (GO:0004950), protein binding (GO:0005515), cytokine binding (GO:0019955)

GO Cellular Component (14): cytoplasm (GO:0005737), lysosome (GO:0005764), early endosome (GO:0005769), late endosome (GO:0005770), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), cell leading edge (GO:0031252), cytoplasmic vesicle (GO:0031410), protein-containing complex (GO:0032991), extracellular exosome (GO:0070062), anchoring junction (GO:0070161), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Early Phase of HIV Life Cycle	1
Axon guidance	1
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
Gastrulation	1
Reproduction	1
Developmental Cell Lineages of the Exocrine Pancreas	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cell migration	2
chemokine (C-X-C motif) ligand 12 signaling pathway	2
chemokine receptor activity	2
chemokine binding	2
endosome	2
response to stress	1
response to decreased oxygen levels	1
leukocyte chemotaxis	1
dendritic cell migration	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
defense response	1
immune system process	1
response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
regulation of biological quality	1
central nervous system development	1
animal organ development	1
head development	1
response to other organism	1
intracellular signaling cassette	1
nervous system development	1
cell differentiation	1
cell adhesion	1
regulation of cellular process	1
regulation of cell migration	1
positive regulation of cell motility	1
C-X-C chemokine receptor CXCR4 signaling pathway	1
plasma membrane organization	1
myelination	1
positive regulation of glial cell differentiation	1
oligodendrocyte differentiation	1
regulation of oligodendrocyte differentiation	1
chemotaxis	1
cellular response to chemical stimulus	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

132 interactions, top by confidence:

A	B	Type	Score
ACKR3	CXCR4	psi-mi:“MI:2364”(proximity)	0.850
CXCR4	ACKR3	psi-mi:“MI:2364”(proximity)	0.850
CXCR4	ACKR3	psi-mi:“MI:0915”(physical association)	0.850
CXCR4	ACKR3	psi-mi:“MI:0403”(colocalization)	0.850
DBN1	CXCR4	psi-mi:“MI:0915”(physical association)	0.700
CXCR4	DBN1	psi-mi:“MI:0403”(colocalization)	0.700
DBN1	CXCR4	psi-mi:“MI:0914”(association)	0.700
CXCR4	CCR5	psi-mi:“MI:0915”(physical association)	0.670
CXCR4	CCR5	psi-mi:“MI:0407”(direct interaction)	0.670
CCR5	CD4	psi-mi:“MI:0914”(association)	0.670
CCR5	CXCR4	psi-mi:“MI:0403”(colocalization)	0.670
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
ADRA1A	CXCR4	psi-mi:“MI:2364”(proximity)	0.610
CXCR4	ADRA1A	psi-mi:“MI:2364”(proximity)	0.610
CXCR4	ADRA1B	psi-mi:“MI:2364”(proximity)	0.610
CXCR4	ADRA1A	psi-mi:“MI:0914”(association)	0.610

BioGRID (270): CXCR4 (Affinity Capture-Western), CXCR4 (Affinity Capture-Western), B2M (Reconstituted Complex), HLA-B (Affinity Capture-Western), CXCR4 (Affinity Capture-MS), CXCR4 (Affinity Capture-MS), CXCR4 (Affinity Capture-MS), CXCR4 (Affinity Capture-MS), CXCR4 (Affinity Capture-MS), CXCR4 (Affinity Capture-MS), CXCR4 (Affinity Capture-MS), CXCR4 (Affinity Capture-MS), CXCR4 (Affinity Capture-MS), CXCR4 (Affinity Capture-MS), CXCR4 (Affinity Capture-MS)

ESM2 similar proteins: A6QNL7, O00574, O08565, O18793, O18983, O19024, O54814, O55193, O62747, O97571, P25930, P32246, P35343, P35350, P35407, P35411, P49238, P51678, P56491, P56498, P61072, P61073, P70658, P79394, Q07FZ4, Q28474, Q2HJ17, Q2KTE1, Q2YEG0, Q3LSL6, Q5ECR9, Q64H34, Q6WN98, Q764M9, Q7YS92, Q7ZXJ7, Q8HZT9, Q8HZU0, Q8HZU1, Q924I3

Diamond homologs: A4FUQ5, B1PHQ8, B9VR26, O08565, O08790, O35210, O35786, O62747, O70129, O75388, O77590, O88416, O88536, O88537, O97571, O97664, P0C7U4, P0C7U5, P21462, P21730, P25025, P25089, P25090, P25095, P25104, P28646, P29089, P29754, P29755, P30555, P30556, P30872, P30873, P30937, P30992, P30993, P31391, P33766, P34976, P35373

SIGNOR signaling

38 interactions.

A	Effect	B	Mechanism
CXCL12	up-regulates	CXCR4	binding
CD74	up-regulates	CXCR4	binding
1-[[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclotetradecane	down-regulates	CXCR4	“chemical inhibition”
CXCR4	up-regulates	Angiogenesis
ERG	“up-regulates quantity by expression”	CXCR4	“transcriptional regulation”
SNAI2	“up-regulates quantity by expression”	CXCR4	“transcriptional regulation”
YBX1	“up-regulates quantity by expression”	CXCR4	“transcriptional regulation”
PRKCD	“down-regulates activity”	CXCR4	phosphorylation
USP14	“up-regulates quantity by stabilization”	CXCR4	deubiquitination
miR-146a	“up-regulates quantity by expression”	CXCR4	“post transcriptional regulation”
hsa-miR-1-5p	“down-regulates quantity by repression”	CXCR4	“post transcriptional regulation”
has-mir-126-3p	“down-regulates quantity by repression”	CXCR4	“post transcriptional regulation”
hsa-miR-133b	“down-regulates quantity by repression”	CXCR4	“post transcriptional regulation”
hsa-miR-139-5p	“down-regulates quantity by repression”	CXCR4	“post transcriptional regulation”
hsa-miR-146a	“down-regulates quantity by repression”	CXCR4	“post transcriptional regulation”
hsa-miR-150-3p	“down-regulates quantity by repression”	CXCR4	“post transcriptional regulation”
hsa-mir-494-3p	“down-regulates quantity by repression”	CXCR4	“post transcriptional regulation”
hsa-miR-9-5p	“down-regulates quantity by repression”	CXCR4	“post transcriptional regulation”
CXCR4	“up-regulates activity”	GNAI1	binding
CXCR4	“up-regulates activity”	GNAI2	binding
CXCR4	“up-regulates activity”	GNAI3	binding
PIM1	“up-regulates quantity”	CXCR4	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 82 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
G alpha (s) signalling events	7	9.7×	8e-04
G alpha (q) signalling events	8	8.7×	8e-04
Class A/1 (Rhodopsin-like receptors)	6	8.4×	5e-03
GPCR ligand binding	6	7.3×	7e-03
GPCR downstream signalling	7	5.7×	7e-03
Signaling by GPCR	7	5.3×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	7	33.2×	4e-07
receptor internalization	6	27.4×	9e-06
calcium-mediated signaling	6	15.5×	2e-04
positive regulation of cytosolic calcium ion concentration	9	14.8×	1e-06
adenylate cyclase-activating G protein-coupled receptor signaling pathway	9	14.3×	2e-06
cell chemotaxis	5	13.0×	2e-03
calcium ion transport	5	12.8×	2e-03
cell surface receptor signaling pathway	12	10.8×	4e-07

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 4 cancer types — DLBCLNOS, MLYM, PAAD, PCM.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	30
Likely pathogenic	9
Uncertain significance	105
Likely benign	73
Benign	10

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1036381	NM_003467.3(CXCR4):c.969dup (p.Ser324fs)	Pathogenic
1067193	NM_003467.3(CXCR4):c.959_960del (p.Val320fs)	Pathogenic
1163801	NM_003467.3(CXCR4):c.988_989del (p.Ser330fs)	Pathogenic
1338437	NM_003467.3(CXCR4):c.1012_1015dup (p.Ser339fs)	Pathogenic
1390084	NM_003467.3(CXCR4):c.963dup (p.Arg322fs)	Pathogenic
1393639	NM_003467.3(CXCR4):c.1014del (p.Ser339fs)	Pathogenic
14020	NM_003467.3(CXCR4):c.1000C>T (p.Arg334Ter)	Pathogenic
14022	NM_003467.3(CXCR4):c.1027G>T (p.Glu343Ter)	Pathogenic
14023	NM_003467.3(CXCR4):c.1013C>G (p.Ser338Ter)	Pathogenic
1453229	NM_003467.3(CXCR4):c.1006G>T (p.Gly336Ter)	Pathogenic
146815	GRCh38/hg38 2q21.3-22.2(chr2:136045480-142845159)x3	Pathogenic
1494228	NM_003467.3(CXCR4):c.1025_1026del (p.Thr342fs)	Pathogenic
1513755	NM_003467.3(CXCR4):c.893_1034dup (p.Glu345_Ser346insProHisProLeuCysPheProTrpSerGlnIleTer)	Pathogenic
3901266	NM_003467.3(CXCR4):c.1037_1040del (p.Glu345_Ser346insTer)	Pathogenic
3902802	NM_003467.3(CXCR4):c.1032_1033del (p.Glu345fs)	Pathogenic
3902803	NM_003467.3(CXCR4):c.976dup (p.Leu326fs)	Pathogenic
3902804	NM_003467.3(CXCR4):c.970del (p.Ser324fs)	Pathogenic
3902805	NM_003467.3(CXCR4):c.970_971insTCCT (p.Ser324fs)	Pathogenic
3902806	NM_003467.3(CXCR4):c.969del (p.Ser324fs)	Pathogenic
3902807	NM_003467.3(CXCR4):c.966_967del (p.Gly323fs)	Pathogenic
3902808	NM_003467.3(CXCR4):c.954del (p.Ser319fs)	Pathogenic
3902809	NM_003467.3(CXCR4):c.951del (p.Thr318fs)	Pathogenic
3902811	NM_003467.3(CXCR4):c.1021del (p.Ser341fs)	Pathogenic
3902812	NM_003467.3(CXCR4):c.1016_1017dup (p.Val340fs)	Pathogenic
3902814	NM_003467.3(CXCR4):c.986_990del (p.Leu329fs)	Pathogenic
3902815	NM_003467.3(CXCR4):c.979_980insG (p.Lys327fs)	Pathogenic
3902816	NM_003467.3(CXCR4):c.977_978del (p.Leu326fs)	Pathogenic
574352	NM_003467.3(CXCR4):c.994G>T (p.Gly332Ter)	Pathogenic
835055	NM_003467.3(CXCR4):c.956_957del (p.Ser319fs)	Pathogenic
988527	NM_003467.3(CXCR4):c.952dup (p.Thr318fs)	Pathogenic

SpliceAI

132 predictions. Top by Δscore:

Variant	Effect	Δscore
2:136116083:T:A	donor_gain	0.9700
2:136116110:T:TA	donor_gain	0.9700
2:136116077:CAA:C	donor_gain	0.9500
2:136116077:CAACT:C	donor_gain	0.9400
2:136116115:ATAT:A	donor_gain	0.8900
2:136116192:G:C	donor_gain	0.8100
2:136116118:T:TA	donor_gain	0.7800
2:136116198:T:TA	donor_gain	0.7400
2:136116014:G:A	donor_gain	0.7200
2:136115909:ATATC:A	acceptor_loss	0.7100
2:136115912:TC:T	acceptor_loss	0.7100
2:136115913:C:CA	acceptor_loss	0.7100
2:136115913:C:CC	acceptor_gain	0.7100
2:136115914:T:C	acceptor_loss	0.7100
2:136115915:G:C	acceptor_loss	0.7000
2:136115925:C:CT	acceptor_loss	0.7000
2:136115926:A:T	acceptor_loss	0.6900
2:136116018:T:A	donor_gain	0.6900
2:136116088:C:A	donor_gain	0.6900
2:136116117:AT:A	donor_gain	0.6800
2:136115908:TATAT:T	acceptor_gain	0.6600
2:136115910:TAT:T	acceptor_gain	0.6600
2:136116087:C:CA	donor_gain	0.6500
2:136116169:A:AC	donor_gain	0.6500
2:136116170:C:CC	donor_gain	0.6500
2:136115999:A:T	donor_gain	0.6400
2:136116137:A:AC	donor_gain	0.6400
2:136116198:T:C	donor_gain	0.6300
2:136115997:A:C	donor_gain	0.6200
2:136116196:CAT:C	donor_gain	0.6200

AlphaMissense

2321 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:136115535:A:C	S131R	0.999
2:136115535:A:T	S131R	0.999
2:136115537:T:G	S131R	0.999
2:136115184:G:C	F248L	0.998
2:136115184:G:T	F248L	0.998
2:136115186:A:G	F248L	0.998
2:136115371:C:T	C186Y	0.998
2:136115447:A:G	W161R	0.998
2:136115447:A:T	W161R	0.998
2:136115527:C:G	R134P	0.998
2:136115602:C:G	C109S	0.998
2:136115603:A:T	C109S	0.998
2:136115622:C:A	W102C	0.998
2:136115622:C:G	W102C	0.998
2:136115653:G:C	P92R	0.998
2:136115774:C:G	G52R	0.998
2:136115148:G:C	S260R	0.997
2:136115148:G:T	S260R	0.997
2:136115150:T:G	S260R	0.997
2:136115167:G:C	P254R	0.997
2:136115167:G:T	P254H	0.997
2:136115371:C:G	C186S	0.997
2:136115372:A:T	C186S	0.997
2:136115562:G:C	S122R	0.997
2:136115562:G:T	S122R	0.997
2:136115564:T:G	S122R	0.997
2:136115601:G:C	C109W	0.997
2:136115602:C:T	C109Y	0.997
2:136115653:G:T	P92H	0.997
2:136115689:A:G	L80P	0.997

dbSNP variants (sampled 300 via entrez): RS1000243153 (2:136117131 C>G), RS1000587550 (2:136118212 T>C,G), RS1001191197 (2:136114584 T>C,G), RS1001278766 (2:136115555 G>C), RS1003252967 (2:136116867 C>T), RS1003585012 (2:136114026 G>A), RS1003641017 (2:136117180 C>T), RS1004309769 (2:136119162 T>C), RS1004710294 (2:136119045 G>A), RS1004721666 (2:136118707 G>A), RS1005373439 (2:136116612 C>T), RS1005714854 (2:136117439 G>A), RS1006306548 (2:136116236 A>G), RS1006878970 (2:136119795 A>G,T), RS1006931429 (2:136119514 A>G,T)

Disease associations

OMIM: gene MIM:162643 | disease phenotypes: MIM:193670

GenCC curated gene-disease

Disease	Classification	Inheritance
WHIM syndrome	Definitive	Autosomal dominant
WHIM syndrome 1	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
WHIM syndrome	Definitive	AD

Mondo (3): WHIM syndrome (MONDO:0023880), WHIM syndrome 1 (MONDO:8000006), (MONDO:0008674)

Orphanet (1): WHIM syndrome (Orphanet:51636)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000055	Abnormal female external genitalia morphology
HP:0000166	Severe periodontitis
HP:0000246	Sinusitis
HP:0000388	Otitis media
HP:0001045	Vitiligo
HP:0001250	Seizure
HP:0001287	Meningitis
HP:0001636	Tetralogy of Fallot
HP:0001875	Decreased total neutrophil count
HP:0001888	Decreased total lymphocyte count
HP:0002070	Limb ataxia
HP:0002090	Pneumonia
HP:0002110	Bronchiectasis
HP:0002167	Abnormal speech pattern
HP:0002172	Postural instability
HP:0002244	Abnormal small intestine morphology
HP:0002718	Recurrent bacterial infections
HP:0002788	Recurrent upper respiratory tract infections
HP:0002840	Lymphadenitis
HP:0003593	Infantile onset
HP:0004313	Decreased circulating immunoglobulin concentration
HP:0004315	Decreased circulating IgG concentration
HP:0005561	Abnormal bone marrow cell morphology
HP:0006532	Recurrent pneumonia
HP:0007010	Poor fine motor coordination
HP:0011850	Parotitis
HP:0011947	Respiratory tract infection
HP:0011992	Abnormal neutrophil morphology

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST000424_7	Multiple sclerosis	1.000000e-07
GCST000669_4	Telomere length	2.000000e-06
GCST002337_113	Amyotrophic lateral sclerosis (sporadic)	3.000000e-06
GCST003424_1	Arthritis (juvenile idiopathic)	3.000000e-14
GCST005150_19	Colorectal cancer	1.000000e-06
GCST005951_44	Body mass index	1.000000e-09
GCST005987_29	Albumin-globulin ratio	2.000000e-11
GCST005990_43	Non-albumin protein levels	1.000000e-11
GCST007327_48	Smoking status (ever vs never smokers)	1.000000e-08
GCST008058_273	Estimated glomerular filtration rate	8.000000e-08
GCST008664_10	Lung function (low FEV1 vs high FEV1)	4.000000e-09
GCST009066_4	Mosaic loss of chromosome Y (Y chromosome dosage)	9.000000e-13
GCST009597_122	Multiple sclerosis	4.000000e-10
GCST010222_1	Attention deficit hyperactivity disorder	2.000000e-06
GCST90002393_204	Monocyte count	2.000000e-11
GCST90002407_65	White blood cell count	2.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0005128	albumin:globulin ratio measurement
EFO:0004318	smoking behavior
EFO:0004314	forced expiratory volume
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0005091	monocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536697	WHIM syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2107 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 111,829 (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
CHEMBL518924	MAVORIXAFOR	4	791
CHEMBL76	CHLOROQUINE	4	58,679
CHEMBL853	ZALCITABINE	4	41,219
CHEMBL1668019	APLAVIROC HYDROCHLORIDE	3	41

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 2 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
CXCR4 EXPRESSION	Docetaxel	Gastric Adenocarcinoma	Resistance	CIViC B	EID949
CXCR4 EXPRESSION	Cisplatin	Lung Non-small Cell Carcinoma	Resistance	CIViC D	EID2912

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2228014	Efficacy	3	bevacizumab	Colorectal Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2228014	CXCR4	3	3.00	1	bevacizumab

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Chemokine receptors

Most potent curated ligand interactions (27 total), top 25:

Ligand	Action	Affinity	Parameter
CXCL12α	Agonist	9.3	pIC50
motixafortide	Antagonist	9.04	pIC50
ulocuplumab	Binding	8.65	pEC50
T140	Inverse agonist	8.6	pIC50
compound XVI [PMID: 38863440]	Antagonist	8.49	pIC50
T134	Antagonist	8.4	pIC50
vMIP-II	Antagonist	8.2	pIC50
TIQ-15	Antagonist	8.2	pIC50
isothiourea-1t	Antagonist	8.1	pIC50
SDF1 P2G	Antagonist	8.05	pKd
mavorixafor	Antagonist	7.96	pKi
[125I]CXCL12β (human)	Full agonist	7.9	pKd
CXCL12β	Full agonist	7.86	pKd
CXCL12H25R (monomer)	Agonist	7.82	pKd
compound 46c [PMID: 29350534]	Antagonist	7.81	pIC50
[125I]CXCL12α (human)	Full agonist	7.45	pKd
isothiourea-1a	Antagonist	7.32	pIC50
CX549	Antagonist	7.3	pIC50
T22	Antagonist	7.3	pIC50
CXCR4 antagonist 22	Antagonist	6.3	pIC50
plerixafor	Antagonist	6.19	pIC50
CXCL12-(1-17)	Full agonist	6.1	pKi
CXCL12-(1-9) dimer	Full agonist	6.1	pKi
ALX40-4C	Partial agonist	6.1	pIC50
CXCL122 (dimer)	Partial agonist	6.0	pKd

Binding affinities (BindingDB)

124 measured of 124 human assays (124 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
tert-butyl 2-[1-[[4-aminobutyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]pyrido[3,4-b]indol-9-yl]acetate	IC50	1 nM	US-9314468: Chemokine receptor modulators
(8S)-N-[[9-[2-(oxan-4-yl)ethyl]pyrido[3,4-b]indol-1-yl]methyl]-N-(3-piperazin-1-ylpropyl)-5,6,7,8-tetrahydroquinolin-8-amine	IC50	1 nM	US-9314468: Chemokine receptor modulators
N’-[[9-(2-morpholin-4-ylethyl)pyrido[3,4-b]indol-1-yl]methyl]-N’-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine	IC50	4 nM	US-9314468: Chemokine receptor modulators
4-[3-[1-[[4-aminobutyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]pyrido[3,4-b]indol-9-yl]propyl]piperazin-2-one	IC50	4 nM	US-9314468: Chemokine receptor modulators
N’-[[9-(cyclopropylmethyl)pyrido[3,4-b]indol-1-yl]methyl]-N’-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine	IC50	4 nM	US-9314468: Chemokine receptor modulators
(8S)-N-[[9-(3-aminopropyl)pyrido[3,4-b]indol-1-yl]methyl]-N-(3-piperazin-1-ylpropyl)-5,6,7,8-tetrahydroquinolin-8-amine	IC50	5 nM	US-9314468: Chemokine receptor modulators
N’-[(9-prop-2-ynylpyrido[3,4-b]indol-1-yl)methyl]-N’-(5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine	IC50	5.5 nM	US-9314468: Chemokine receptor modulators
2-[1-[[4-aminobutyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]pyrido[3,4-b]indol-9-yl]-1-morpholin-4-ylethanone	IC50	5.6 nM	US-9314468: Chemokine receptor modulators
N’-[[9-(2-piperazin-1-ylethyl)pyrido[3,4-b]indol-1-yl]methyl]-N’-(5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine	IC50	5.7 nM	US-9314468: Chemokine receptor modulators
2-[1-[[4-aminobutyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]pyrido[3,4-b]indol-9-yl]acetamide	IC50	5.8 nM	US-9314468: Chemokine receptor modulators
N’-[[9-(3-aminopropyl)pyrido[3,4-b]indol-1-yl]methyl]-N’-(5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine	IC50	7.3 nM	US-9314468: Chemokine receptor modulators
N’-[[9-(2-morpholin-4-ylethyl)pyrido[3,4-b]indol-1-yl]methyl]-N’-(5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine	IC50	7.7 nM	US-9314468: Chemokine receptor modulators
2-[1-[[4-aminobutyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]pyrido[3,4-b]indol-9-yl]-1-iodosylethanone	IC50	8.1 nM	US-9314468: Chemokine receptor modulators
N’-[[9-(3-piperazin-1-ylpropyl)pyrido[3,4-b]indol-1-yl]methyl]-N’-(5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine	IC50	8.3 nM	US-9314468: Chemokine receptor modulators
N’-[(9-prop-2-ynylpyrido[3,4-b]indol-1-yl)methyl]-N’-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine	IC50	9 nM	US-9314468: Chemokine receptor modulators
2-[1-[[3-piperazin-1-ylpropyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]pyrido[3,4-b]indol-9-yl]acetamide	IC50	9 nM	US-9314468: Chemokine receptor modulators
2-[1-[[4-aminobutyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]pyrido[3,4-b]indol-9-yl]-1-[(2S,6R)-2,6-dimethylmorpholin-4-yl]ethanone	IC50	9.9 nM	US-9314468: Chemokine receptor modulators
N’-[(9-methylpyrido[3,4-b]indol-1-yl)methyl]-N’-(5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine	IC50	10 nM	US-9314468: Chemokine receptor modulators
2-[1-[[4-aminobutyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]pyrido[3,4-b]indol-9-yl]ethanol	IC50	11 nM	US-9314468: Chemokine receptor modulators
2-[1-[[4-aminobutyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]pyrido[3,4-b]indol-9-yl]-1-(4-methylpiperazin-1-yl)ethanone	IC50	11 nM	US-9314468: Chemokine receptor modulators
2-[1-[[4-aminobutyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]pyrido[3,4-b]indol-9-yl]-1-morpholin-4-ylethanone	IC50	12 nM	US-9314468: Chemokine receptor modulators
2-[1-[[4-aminobutyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]pyrido[3,4-b]indol-9-yl]-N-piperidin-4-ylacetamide	IC50	12 nM	US-9314468: Chemokine receptor modulators
2-[1-[[4-aminobutyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]pyrido[3,4-b]indol-9-yl]-1-(4-hydroxypiperidin-1-yl)ethanone	IC50	12 nM	US-9314468: Chemokine receptor modulators
2-[1-[[3-piperazin-1-ylpropyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]pyrido[3,4-b]indol-9-yl]ethanol	IC50	12 nM	US-9314468: Chemokine receptor modulators
N’-[[9-[2-(oxan-4-yl)ethyl]pyrido[3,4-b]indol-1-yl]methyl]-N’-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine	IC50	13 nM	US-9314468: Chemokine receptor modulators
(8S)-N-[[9-(cyclopropylmethyl)pyrido[3,4-b]indol-1-yl]methyl]-N-(3-piperazin-1-ylpropyl)-5,6,7,8-tetrahydroquinolin-8-amine	IC50	14 nM	US-9314468: Chemokine receptor modulators
ethyl 2-[1-[[4-aminobutyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]pyrido[3,4-b]indol-9-yl]acetate	IC50	15 nM	US-9314468: Chemokine receptor modulators
N’-[[9-(3-piperazin-1-ylpropyl)pyrido[3,4-b]indol-1-yl]methyl]-N’-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine	IC50	15 nM	US-9314468: Chemokine receptor modulators
1-morpholin-4-yl-2-[1-[[3-piperazin-1-ylpropyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]pyrido[3,4-b]indol-9-yl]ethanone	IC50	15 nM	US-9314468: Chemokine receptor modulators
2-[1-[[4-aminobutyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]pyrido[3,4-b]indol-9-yl]acetamide	IC50	17 nM	US-9314468: Chemokine receptor modulators
N-(3-piperazin-1-ylpropyl)-N-(9H-pyrido[3,4-b]indol-1-ylmethyl)-5,6,7,8-tetrahydroquinolin-8-amine	IC50	18 nM	US-9314468: Chemokine receptor modulators
1-[3-[1-[[4-aminobutyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]pyrido[3,4-b]indol-9-yl]propyl]piperazin-2-one	IC50	20 nM	US-9314468: Chemokine receptor modulators
N’-[[9-(2-methoxyethyl)pyrido[3,4-b]indol-1-yl]methyl]-N’-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine	IC50	20 nM	US-9314468: Chemokine receptor modulators
N’-[[9-(3-aminopropyl)pyrido[3,4-b]indol-1-yl]methyl]-N’-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine	IC50	21 nM	US-9314468: Chemokine receptor modulators
2-[1-[[4-aminobutyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]pyrido[3,4-b]indol-9-yl]-N-(oxan-4-yl)acetamide	IC50	21 nM	US-9314468: Chemokine receptor modulators
N’-[(9-methylpyrido[3,4-b]indol-1-yl)methyl]-N’-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine	IC50	22 nM	US-9314468: Chemokine receptor modulators
2-[1-[[4-aminobutyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]pyrido[3,4-b]indol-9-yl]acetic acid	IC50	22 nM	US-9314468: Chemokine receptor modulators
(8S)-N-[[9-(2-morpholin-4-ylethyl)pyrido[3,4-b]indol-1-yl]methyl]-N-(3-piperazin-1-ylpropyl)-5,6,7,8-tetrahydroquinolin-8-amine	IC50	24 nM	US-9314468: Chemokine receptor modulators
N-[[9-(2-morpholin-4-ylethyl)pyrido[3,4-b]indol-1-yl]methyl]-N-(3-piperazin-1-ylpropyl)-5,6,7,8-tetrahydroquinolin-8-amine	IC50	24 nM	US-9314468: Chemokine receptor modulators
N-(oxan-4-yl)-2-[1-[[3-piperazin-1-ylpropyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]pyrido[3,4-b]indol-9-yl]acetamide	IC50	26 nM	US-9314468: Chemokine receptor modulators
2-[1-[[3-piperazin-1-ylpropyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]pyrido[3,4-b]indol-9-yl]acetic acid	IC50	26 nM	US-9314468: Chemokine receptor modulators
N’-(9H-pyrido[3,4-b]indol-1-ylmethyl)-N’-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine	IC50	30 nM	US-9314468: Chemokine receptor modulators
2-[1-[[4-aminobutyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]pyrido[3,4-b]indol-9-yl]-1-(4-methylpiperazin-1-yl)ethanone	IC50	30 nM	US-9314468: Chemokine receptor modulators
4-[3-[[9-(3-aminopropyl)pyrido[3,4-b]indol-1-yl]methyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]propyl]piperazin-2-one	IC50	30 nM	US-9314468: Chemokine receptor modulators
N’-[[9-(pyridin-2-ylmethyl)pyrido[3,4-b]indol-1-yl]methyl]-N’-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine	IC50	31 nM	US-9314468: Chemokine receptor modulators
tert-butyl 2-[1-[[3-piperazin-1-ylpropyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]pyrido[3,4-b]indol-9-yl]acetate	IC50	37 nM	US-9314468: Chemokine receptor modulators
1,1-dimethyl-3-[4-[9H-pyrido[3,4-b]indol-1-ylmethyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]butyl]urea	IC50	38 nM	US-9314468: Chemokine receptor modulators
1-morpholin-4-yl-2-[1-[[3-piperazin-1-ylpropyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]pyrido[3,4-b]indol-9-yl]ethanone	IC50	44 nM	US-9314468: Chemokine receptor modulators
2-[3-[1-[[3-piperazin-1-ylpropyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]pyrido[3,4-b]indol-9-yl]propyl]isoindole-1,3-dione	IC50	44 nM	US-9314468: Chemokine receptor modulators
1-[3-[1-[[3-piperazin-1-ylpropyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]pyrido[3,4-b]indol-9-yl]propyl]piperazin-2-one	IC50	44 nM	US-9314468: Chemokine receptor modulators

ChEMBL bioactivities

1376 potent at pChembl≥5 of 1476 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	IC50	0.02	nM	CHEMBL4751485
9.92	EC50	0.12	nM	CHEMBL5612607
9.72	EC50	0.19	nM	CHEMBL5611972
9.72	EC50	0.19	nM	CHEMBL5612623
9.62	EC50	0.24	nM	CHEMBL5613902
9.60	IC50	0.25	nM	CHEMBL4799439
9.52	IC50	0.3	nM	CHEMBL237830
9.52	EC50	0.3	nM	CHEMBL237830
9.47	IC50	0.34	nM	CHEMBL1242210
9.40	IC50	0.4	nM	CHEMBL4792975
9.40	EC50	0.4	nM	CHEMBL2372985
9.30	EC50	0.5	nM	CHEMBL2372997
9.30	IC50	0.5	nM	CHEMBL2062277
9.22	EC50	0.6	nM	CHEMBL2372993
9.22	IC50	0.6	nM	CHEMBL393882
9.21	IC50	0.61	nM	CHEMBL1242211
9.21	Ki	0.61	nM	CHEMBL1242211
9.21	IC50	0.61	nM	CHEMBL2062277
9.14	IC50	0.73	nM	CHEMBL4203703
9.10	IC50	0.8	nM	CHEMBL2062277
9.10	IC50	0.8	nM	CHEMBL1802333
9.09	IC50	0.81	nM	PLERIXAFOR
9.06	IC50	0.87	nM	CHEMBL1242210
9.00	IC50	1	nM	CHEMBL3091683
9.00	IC50	1	nM	CHEMBL3956608
9.00	IC50	1	nM	CHEMBL3938042
9.00	IC50	1	nM	CHEMBL4163246
9.00	EC50	1	nM	CHEMBL4074140
9.00	EC50	1	nM	CHEMBL5614258
9.00	EC50	1	nM	CHEMBL5613857
9.00	IC50	1	nM	CHEMBL5612681
9.00	ED50	1	nM	CHEMBL513863
9.00	IC50	1	nM	CHEMBL1202231
9.00	IC50	1	nM	CHEMBL2062277
8.97	IC50	1.07	nM	CHEMBL1242210
8.96	IC50	1.1	nM	CHEMBL4799191
8.96	IC50	1.1	nM	CHEMBL460491
8.92	EC50	1.2	nM	CHEMBL2373004
8.92	IC50	1.2	nM	CHEMBL2062277
8.89	EC50	1.3	nM	CHEMBL5613412
8.89	IC50	1.3	nM	CHEMBL1644092
8.89	IC50	1.3	nM	CHEMBL2062277
8.87	IC50	1.36	nM	CHEMBL2012527
8.82	IC50	1.5	nM	CHEMBL4078698
8.82	IC50	1.5	nM	CHEMBL6175379
8.82	IC50	1.5	nM	CHEMBL2062277
8.81	IC50	1.56	nM	CHEMBL2012525
8.80	IC50	1.6	nM	CHEMBL4457992
8.80	IC50	1.6	nM	CHEMBL5172755
8.80	IC50	1.6	nM	CHEMBL2062277

PubChem BioAssay actives

1220 with measured affinity, of 3503 total; 50 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
(8S)-N-methyl-N-[[2-methyl-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine	1702401: Antagonist activity at CXCR4 in human CD4-positive T cells assessed as inhibition of CXCL12-induced calcium signal incubated for 20 mins by FLIPR assay	ic50	<0.0001	uM
1-[[6-methyl-5-(5-methylsulfanyl-1,3,4-oxadiazol-2-yl)-2-pyridinyl]methyl]-3-(4-nitrophenyl)urea	2124396: Antagonist activity at CXCR4 (unknown origin) expressed in human HEK293T cells assessed as intracellular calcium flux by FLIPR assay	ec50	0.0001	uM
N-methyl-N-[[2-methyl-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]methyl]quinolin-8-amine	2124396: Antagonist activity at CXCR4 (unknown origin) expressed in human HEK293T cells assessed as intracellular calcium flux by FLIPR assay	ec50	0.0002	uM
6-methyl-5-(5-methylsulfanyl-1,3,4-oxadiazol-2-yl)pyridin-2-amine;2,2,2-trifluoroacetic acid	2124396: Antagonist activity at CXCR4 (unknown origin) expressed in human HEK293T cells assessed as intracellular calcium flux by FLIPR assay	ec50	0.0002	uM
[6-methyl-5-(5-methylsulfanyl-1,3,4-oxadiazol-2-yl)-2-pyridinyl]methyl N-(4-nitrophenyl)carbamate	2124396: Antagonist activity at CXCR4 (unknown origin) expressed in human HEK293T cells assessed as intracellular calcium flux by FLIPR assay	ec50	0.0002	uM
N-[[4-[(pyridin-2-ylamino)methyl]phenyl]methyl]pyridin-2-amine	1501134: Binding affinity to CXCR4 in human MDA-MB-231 cells preincubated for 15 mins followed by biotinylated TN41003 addition measured after 30 mins by rhodamine staining-based assay	ic50	0.0003	uM
[5-(4-methylpiperazin-1-yl)-2-[[methyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]imidazo[1,2-a]pyridin-3-yl]methanol	508869: Inhibition of CXCR4-mediated chemotaxis in SDF1-stimulated human U937 cells treated 15 mins before SDF1 challenge measured after 2 hrs by luminescence assay	ic50	0.0003	uM
2-methyl-4-(4-methylpiperazin-1-yl)-6-[[(2S)-2-(3-methyl-2-pyridinyl)pyrrolidin-1-yl]methyl]pyrimidine	1742058: Antagonist activity at CXCR4 in human CD4-positive T cells assessed as inhibition of CXCL12-induced cytosolic calcium flux preincubated for 20 mins followed by CXCL12 addition by calcium 4 dye based FLIPR TETRA analysis	ic50	0.0003	uM
1-methyl-4-[2-methyl-6-[[(2S)-2-(3-methyl-2-pyridinyl)pyrrolidin-1-yl]methyl]pyrimidin-4-yl]-1,4-diazepane	1742058: Antagonist activity at CXCR4 in human CD4-positive T cells assessed as inhibition of CXCL12-induced cytosolic calcium flux preincubated for 20 mins followed by CXCL12 addition by calcium 4 dye based FLIPR TETRA analysis	ic50	0.0004	uM
(3S,6R,9S,12R,15S,20S,23S,26S,29S,32R)-6-(4-aminobutyl)-N-[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-15-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-2-naphthalen-2-ylacetyl]amino]-3,9,23-tris[3-(carbamoylamino)propyl]-26-[3-(diaminomethylideneamino)propyl]-12,29-bis[(4-hydroxyphenyl)methyl]-2,5,8,11,14,22,25,28,31-nonaoxo-17,18-dithia-1,4,7,10,13,21,24,27,30-nonazabicyclo[30.3.0]pentatriacontane-20-carboxamide	104272: Effective concentration for 50% protection of HIV-induced cytopathogenicity in MT-4 cells on the MTT assay	ec50	0.0004	uM
2,3-dihydroxybutanedioic acid;N-[[4-[[1H-imidazol-2-ylmethyl-[(1-methylimidazol-2-yl)methyl]amino]methyl]phenyl]methyl]-N-methyl-N’,N’-dipropylbutane-1,4-diamine	559981: Inhibition of Mab 12G5 binding to CXCR4 D181A mutant expressed in HEK293 cells	ic50	0.0005	uM
(2S)-2-[[(3S,6R,9S,12R,15S,20S,23S,26S,29S,32R)-6-(4-aminobutyl)-15-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-2-naphthalen-2-ylacetyl]amino]-3,9,23-tris[3-(carbamoylamino)propyl]-26-[3-(diaminomethylideneamino)propyl]-12,29-bis[(4-hydroxyphenyl)methyl]-2,5,8,11,14,22,25,28,31-nonaoxo-17,18-dithia-1,4,7,10,13,21,24,27,30-nonazabicyclo[30.3.0]pentatriacontane-20-carbonyl]amino]-5-(diaminomethylideneamino)pentanoic acid	104272: Effective concentration for 50% protection of HIV-induced cytopathogenicity in MT-4 cells on the MTT assay	ec50	0.0005	uM
N-[[4-[[1H-imidazol-2-ylmethyl-[(1-methylimidazol-2-yl)methyl]amino]methyl]phenyl]methyl]-N-methyl-N’,N’-dipropylbutane-1,4-diamine	1383297: Displacement of [125I]SDF-1alpha from CXCR4 (unknown origin) expressed in CHO cells by scintillation counting analysis	ic50	0.0006	uM
(3R,6S,9S,12S,15R,20R,23S,26S,29S,32S)-3,6-bis(4-aminobutyl)-N-[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]-15-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-26-(3-carbamimidamidopropyl)-9,23-bis[3-(carbamoylamino)propyl]-12,29-bis[(4-hydroxyphenyl)methyl]-2,5,8,11,14,22,25,28,31-nonaoxo-17,18-dithia-1,4,7,10,13,21,24,27,30-nonazabicyclo[30.3.0]pentatriacontane-20-carboxamide	303360: Inhibition of CXCR4 in MDA-MB-231 cells	ic50	0.0006	uM
(3S,6R,9S,12R,15S,20S,23S,26S,29S,32R)-3,6-bis(4-aminobutyl)-N-[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-15-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-2-naphthalen-2-ylacetyl]amino]-9,23-bis[3-(carbamoylamino)propyl]-26-[3-(diaminomethylideneamino)propyl]-12,29-bis[(4-hydroxyphenyl)methyl]-2,5,8,11,14,22,25,28,31-nonaoxo-17,18-dithia-1,4,7,10,13,21,24,27,30-nonazabicyclo[30.3.0]pentatriacontane-20-carboxamide	104272: Effective concentration for 50% protection of HIV-induced cytopathogenicity in MT-4 cells on the MTT assay	ec50	0.0006	uM
(8S)-N-methyl-N-[[6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine	1383114: Antagonist activity at CXCR4 in human CD4+ T cells assessed as inhibition of CXCL12-mediated cytosolic calcium level preincubated with compounds followed by CXCL12 stimulation by calcium 4 dye-based FLIPR assay	ic50	0.0007	uM
4-N-[[4-[[(2-chloro-5-fluoropyrimidin-4-yl)amino]methyl]phenyl]methyl]-2-N-(2-morpholin-4-ylethyl)pyrimidine-2,4-diamine	604427: Antagonist activity at human CXCR4 expressed in human U87 cells expressing CD4 assessed as inhibition of CXCL12-induced cAMP production pretreated for 15 mins before forskolin challenge by TR-FRET analysis	ic50	0.0008	uM
Plerixafor	1957039: Inhibition of CXCR4 (unknown origin)	ic50	0.0008	uM
(3R,6S,9S,12S,15R,20R,23S,26S,29S,32S)-3,6-bis(4-aminobutyl)-N-[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]-15-[[(2S)-2-[[(2S)-5-carbamimidamido-2-[[(2S)-5-carbamimidamido-2-[(4-fluorobenzoyl)amino]pentanoyl]amino]pentanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-9,26-bis(3-carbamimidamidopropyl)-23-[3-(carbamoylamino)propyl]-12,29-bis[(4-hydroxyphenyl)methyl]-2,5,8,11,14,22,25,28,31-nonaoxo-17,18-dithia-1,4,7,10,13,21,24,27,30-nonazabicyclo[30.3.0]pentatriacontane-20-carboxamide	1501130: Antagonist activity at CXCR4 (unknown origin)	ic50	0.0010	uM
N-[[4-[[(2,4-difluorophenyl)sulfonylamino]methyl]phenyl]methyl]pyrimidine-5-carboxamide	2124396: Antagonist activity at CXCR4 (unknown origin) expressed in human HEK293T cells assessed as intracellular calcium flux by FLIPR assay	ec50	0.0010	uM
(4S,7S,10S,13S,16S)-16-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]-13-[3-(diaminomethylideneamino)propyl]-7-(1H-imidazol-5-ylmethyl)-3,3-dimethyl-10-(naphthalen-2-ylmethyl)-6,9,12,15-tetraoxo-1,2-dithia-5,8,11,14-tetrazacycloheptadecane-4-carboxylic acid	2125784: Antagonist activity at CXCR4 in human CCRF-CEM cells assessed as inhibition of anti-CXCR4 binding preincubated with compound for 45 mins followed by anti-CXCR4 PE antibody addition and measured after 30 mins by fluorescence based competitive binding assay	ic50	0.0010	uM
3-[3-(5-methylsulfanyl-1,3,4-oxadiazol-2-yl)-2-pyridinyl]propan-1-ol	2124396: Antagonist activity at CXCR4 (unknown origin) expressed in human HEK293T cells assessed as intracellular calcium flux by FLIPR assay	ec50	0.0010	uM
N-[[6-methyl-5-(5-methylsulfanyl-1,3,4-oxadiazol-2-yl)-2-pyridinyl]methyl]benzamide	2124396: Antagonist activity at CXCR4 (unknown origin) expressed in human HEK293T cells assessed as intracellular calcium flux by FLIPR assay	ec50	0.0010	uM
7-[[4-(4,7,10,17-tetrazabicyclo[11.3.1]heptadeca-1(17),13,15-trien-7-ylmethyl)phenyl]methyl]-4,7,10,17-tetrazabicyclo[11.3.1]heptadeca-1(17),13,15-triene;hydrobromide	47536: Inhibitory activity against CX3C chemokine receptor 4-specific monoclonal antibody 12G5 (mAb-12G5) binding to human chemokinin receptor CXCR4 in lymphocytic SUP-T1 cells	ic50	0.0010	uM
N-(pyridin-2-ylmethyl)-N’-[[(3R)-1,2,3,4-tetrahydroisoquinolin-3-yl]methyl]-N’-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine	1056194: Antagonist activity at CXCR4 in human Chem-1 cells assessed as inhibition of SDF-1alpha-mediated calcium flux preincubated for 10 mins by FLIPR assay	ic50	0.0010	uM
5-fluoro-2-methyl-4-(4-methylpiperazin-1-yl)-6-[[(2S)-2-(3-methyl-2-pyridinyl)pyrrolidin-1-yl]methyl]pyrimidine	1742058: Antagonist activity at CXCR4 in human CD4-positive T cells assessed as inhibition of CXCL12-induced cytosolic calcium flux preincubated for 20 mins followed by CXCL12 addition by calcium 4 dye based FLIPR TETRA analysis	ic50	0.0011	uM
(6,6-dimethyl-5H-imidazo[2,1-b][1,3]thiazol-3-yl)methyl N,N’-dicyclohexylcarbamimidothioate	1957045: Inhibition of wild type CXCR4 (unknown origin)	ic50	0.0011	uM
(3S,6R,9S,12R,15S,20S,23S,26S,29S,32R)-6-(4-aminobutyl)-15-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-(carbamoylamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-2-naphthalen-2-ylacetyl]amino]-N-[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-3,23-bis[3-(carbamoylamino)propyl]-9,26-bis[3-(diaminomethylideneamino)propyl]-12,29-bis[(4-hydroxyphenyl)methyl]-2,5,8,11,14,22,25,28,31-nonaoxo-17,18-dithia-1,4,7,10,13,21,24,27,30-nonazabicyclo[30.3.0]pentatriacontane-20-carboxamide	104272: Effective concentration for 50% protection of HIV-induced cytopathogenicity in MT-4 cells on the MTT assay	ec50	0.0012	uM
7-fluoro-N-methyl-N-[[2-methyl-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]methyl]-5,6-dihydroquinolin-8-amine	2124396: Antagonist activity at CXCR4 (unknown origin) expressed in human HEK293T cells assessed as intracellular calcium flux by FLIPR assay	ec50	0.0013	uM
N-[[4-(aminomethyl)-1,3-oxazol-5-yl]methyl]-N-(1H-benzimidazol-2-ylmethyl)-5,6,7,8-tetrahydroquinolin-8-amine	551533: Antagonist activity at CXCR4 in human CEM-CCRF cells expressing CD4 assessed as inhibition of SDF-1-induced Ca2+ signaling	ic50	0.0013	uM
(2S)-2-[[(3R,6S,9S,12S,15R,20R,23S,26S,29S,32S)-3,6-bis(4-aminobutyl)-15-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-23-[4-[[(2S)-5-carbamimidamido-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]pentanoyl]amino]butyl]-9,26-bis(3-carbamimidamidopropyl)-12,29-bis[(4-hydroxyphenyl)methyl]-2,5,8,11,14,22,25,28,31-nonaoxo-17,18-dithia-1,4,7,10,13,24,27,30-octazabicyclo[30.3.0]pentatriacontane-20-carbonyl]amino]-5-carbamimidamidopentanoic acid	652464: Displacement of [125I]-SDF-1alpha from human CXCR4 receptor expressed in HEK293 cells after 1 hr by gamma counting	ic50	0.0014	uM
(4R,7S,10S,13S,16S)-16-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]-10-benzyl-13-[3-(diaminomethylideneamino)propyl]-3,3-dimethyl-7-(naphthalen-2-ylmethyl)-6,9,12,15-tetraoxo-1,2-dithia-5,8,11,14-tetrazacycloheptadecane-4-carboxylic acid	1477220: Inhibition of anti-CXCR4 PE antibody clone 12G5 binding to CXCR4 in human CCRF-CEM cells preincubated for 30 mins followed by anti-CXCR4 PE antibody clone 12G5 addition measured after 30 mins by flow cytometric method	ic50	0.0015	uM
(2S)-N-[[4-[[3-(cyclohexylamino)propylamino]methyl]phenyl]methyl]-5-(diaminomethylideneamino)-2-(pyridin-2-ylmethylamino)pentanamide	1902006: Antagonist activity at CXCR4 receptor in SDF-1alpha-stimulated human SUP-T1 cells measured by calcium mobilization assay	ic50	0.0016	uM
N,N-bis(pyridin-2-ylmethyl)-1-[5-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)naphthalen-2-yl]methanamine	1572815: Competitive inhibition of TAMRAAc-TZ14011 binding to CXCR4 (unknown origin) expressed in CHO cells in presence of ZnCl2 by NanoBRET assay relative to control	ic50	0.0016	uM
(2S)-2-[[(3R,6S,9S,12S,15R,20R,23S,26S,29S,32S)-3,6-bis(4-aminobutyl)-15-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-9,26-bis(3-carbamimidamidopropyl)-23-[3-(carbamoylamino)propyl]-12,29-bis[(4-hydroxyphenyl)methyl]-2,5,8,11,14,22,25,28,31-nonaoxo-17,18-dithia-1,4,7,10,13,24,27,30-octazabicyclo[30.3.0]pentatriacontane-20-carbonyl]amino]-5-carbamimidamidopentanoic acid	652464: Displacement of [125I]-SDF-1alpha from human CXCR4 receptor expressed in HEK293 cells after 1 hr by gamma counting	ic50	0.0016	uM
2-methyl-4-(4-methylpiperazin-1-yl)-6-[[(2S)-2-(3-methyl-2-pyridinyl)pyrrolidin-1-yl]methyl]pyrimidine-5-carbonitrile	1742058: Antagonist activity at CXCR4 in human CD4-positive T cells assessed as inhibition of CXCL12-induced cytosolic calcium flux preincubated for 20 mins followed by CXCL12 addition by calcium 4 dye based FLIPR TETRA analysis	ic50	0.0018	uM
2-[3-[(2R,5S,8S,14R)-5-[3-(diaminomethylideneamino)propyl]-14-[(4-hydroxyphenyl)methyl]-1-methyl-8-(naphthalen-2-ylmethyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]propyl]guanidine	646504: Displacement of [125I]-CPCR4 from CXCR4 receptor in human Jurkat cells after 2 hrs by gamma counting	ic50	0.0020	uM
N’-[[(2S)-4-(benzenesulfonyl)piperazin-2-yl]methyl]-N’-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine	1252137: Antagonist activity at CXCR4 in human Chem-1 cells assessed as inhibition of CXCL12-induced calcium flux	ic50	0.0020	uM
N’-[[(2S)-4-(4-chlorophenyl)sulfonylpiperazin-2-yl]methyl]-N’-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine	1252137: Antagonist activity at CXCR4 in human Chem-1 cells assessed as inhibition of CXCL12-induced calcium flux	ic50	0.0020	uM
(8S)-N-methyl-N-[[1-[(1-propan-2-ylpiperidin-3-yl)methyl]benzimidazol-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine	2124393: Inhibition of CXCR4 receptor (unknown origin)	ic50	0.0020	uM
N,N’-bis[3-[(2R,5S,8S,14R)-5-(3-carbamimidamidopropyl)-14-[(4-hydroxyphenyl)methyl]-1-methyl-8-(naphthalen-2-ylmethyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]propyl]decanediamide	646504: Displacement of [125I]-CPCR4 from CXCR4 receptor in human Jurkat cells after 2 hrs by gamma counting	ic50	0.0020	uM
[(3S)-3-[[4-aminobutyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]piperazin-1-yl]-phenylmethanone	1252137: Antagonist activity at CXCR4 in human Chem-1 cells assessed as inhibition of CXCL12-induced calcium flux	ic50	0.0020	uM
N-[[4-(benzenesulfonamidomethyl)phenyl]methyl]-4-fluorobenzamide	2124396: Antagonist activity at CXCR4 (unknown origin) expressed in human HEK293T cells assessed as intracellular calcium flux by FLIPR assay	ec50	0.0021	uM
(6,6-dimethyl-5H-imidazo[2,1-b][1,3]thiazol-3-yl)methyl N,N’-di(cycloheptyl)carbamimidothioate	408926: Activity at CXCR4 in human CEM cells assessed as inhibition of CXCL12-induced calcium mobilization	ic50	0.0021	uM
(2S)-2-[[(3R,6S,9S,12S,15R,20R,23S,26S,29S,32S)-3,6-bis(4-aminobutyl)-15-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-9,26-bis(3-carbamimidamidopropyl)-23-[4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]butyl]-12,29-bis[(4-hydroxyphenyl)methyl]-2,5,8,11,14,22,25,28,31-nonaoxo-17,18-dithia-1,4,7,10,13,24,27,30-octazabicyclo[30.3.0]pentatriacontane-20-carbonyl]amino]-5-carbamimidamidopentanoic acid	652464: Displacement of [125I]-SDF-1alpha from human CXCR4 receptor expressed in HEK293 cells after 1 hr by gamma counting	ic50	0.0022	uM
N-methyl-N-[[6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine;hydrochloride	1383114: Antagonist activity at CXCR4 in human CD4+ T cells assessed as inhibition of CXCL12-mediated cytosolic calcium level preincubated with compounds followed by CXCL12 stimulation by calcium 4 dye-based FLIPR assay	ic50	0.0023	uM
6-[3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-5-yl)propanoylamino]-N-[3-[3-[[methyl-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]isoquinolin-4-yl]propyl]hexanamide	2029422: Binding affinity to Nluc-CXCR4 (unknown origin) stably expressed in HEK293G cells using furimazine as substrate incubated for 2 hrs followed by substrate addition in presence of (6,6-dimethyl-5,6-dihydroimidazo[2,1-b]thiazol-3-yl)methyl (Z)-N,N’-dicyclohexylcarbamimidothioate by NanoBRET assay	ki	0.0026	uM
2-methyl-6-[[(2S)-2-(3-methyl-2-pyridinyl)pyrrolidin-1-yl]methyl]-N-(2-morpholin-4-ylethyl)pyrimidin-4-amine	1742058: Antagonist activity at CXCR4 in human CD4-positive T cells assessed as inhibition of CXCL12-induced cytosolic calcium flux preincubated for 20 mins followed by CXCL12 addition by calcium 4 dye based FLIPR TETRA analysis	ic50	0.0027	uM
2-methyl-4-(4-methylpiperazin-1-yl)-6-[[(2S)-2-pyridin-2-ylpyrrolidin-1-yl]methyl]pyrimidine	1742058: Antagonist activity at CXCR4 in human CD4-positive T cells assessed as inhibition of CXCL12-induced cytosolic calcium flux preincubated for 20 mins followed by CXCL12 addition by calcium 4 dye based FLIPR TETRA analysis	ic50	0.0027	uM
(3S,6R,9S,12R,15S,20S,23S,26S,29S,32R)-6-(4-aminobutyl)-N-[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-15-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-2-naphthalen-2-ylacetyl]amino]-3,23,26-tris[3-(carbamoylamino)propyl]-9-[3-(diaminomethylideneamino)propyl]-12,29-bis[(4-hydroxyphenyl)methyl]-2,5,8,11,14,22,25,28,31-nonaoxo-17,18-dithia-1,4,7,10,13,21,24,27,30-nonazabicyclo[30.3.0]pentatriacontane-20-carboxamide	104272: Effective concentration for 50% protection of HIV-induced cytopathogenicity in MT-4 cells on the MTT assay	ec50	0.0027	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases reaction, increases expression, decreases response to substance, decreases expression	6
Valproic Acid	decreases expression, affects expression, increases expression, affects cotreatment	6
Oxygen	decreases reaction, increases expression	5
trichostatin A	increases expression, decreases expression, affects cotreatment	4
nickel sulfate	affects expression, increases expression	4
Decitabine	decreases expression, decreases reaction, affects expression, affects methylation, affects cotreatment (+1 more)	4
Cadmium	increases expression, decreases expression, increases abundance, affects cotreatment	4
Tetrachlorodibenzodioxin	decreases reaction, increases expression, affects cotreatment, decreases expression	4
plerixafor	affects localization, decreases expression, affects binding, decreases activity, decreases reaction (+1 more)	3
(+)-JQ1 compound	decreases expression	3
Resveratrol	decreases reaction, increases expression, decreases expression	3
Arsenic Trioxide	affects expression, decreases reaction, increases expression, decreases expression, affects reaction	3
Vorinostat	affects cotreatment, decreases expression	3
Benzo(a)pyrene	affects expression, increases expression, increases methylation	3
Cisplatin	affects cotreatment, increases expression, affects expression	3
Dexamethasone	decreases reaction, increases expression	3
Dinitrochlorobenzene	decreases expression, increases expression	3
Tretinoin	affects expression, decreases expression, increases expression	3
methylmercuric chloride	decreases expression	2
bisphenol A	decreases reaction, increases expression, decreases response to substance	2
deoxynivalenol	increases expression	2
lead acetate	decreases expression, affects cotreatment	2
tributyltin	increases expression	2
mangiferin	affects expression, affects reaction, decreases reaction, increases expression	2
3,3’-diindolylmethane	affects methylation, decreases reaction, increases expression	2
sodium arsenite	affects cotreatment, decreases expression	2
cobaltous chloride	increases expression, decreases reaction	2
mercuric bromide	decreases expression, affects cotreatment	2
deguelin	decreases reaction, increases expression, decreases expression	2
entinostat	decreases expression, affects cotreatment	2

ChEMBL screening assays

560 unique, capped per target: 386 binding, 174 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1010853	Binding	Inhibition of CXCR4 receptor	Discovery of a potent, selective and orally bioavailable 3,9-diazaspiro[5.5]undeca-2-one CCR5 antagonist. — Bioorg Med Chem Lett
CHEMBL1031464	Functional	Antagonist activity at CXCR4 in human Jurkat cells assessed as inhibition of SDF1-induced cell migration	64Cu-AMD3100–a novel imaging agent for targeting chemokine receptor CXCR4. — Bioorg Med Chem

Cellosaurus cell lines

34 cell lines: 21 cancer cell line, 8 spontaneously immortalized cell line, 5 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1D99	HOS-CD4-Fusin	Cancer cell line	Female
CVCL_1E08	GHOST(3).R3/X4/R5	Cancer cell line	Female
CVCL_1E10	GHOST(3).X4/R5	Cancer cell line	Female
CVCL_1E16	3T3.T4.CXCR4	Transformed cell line	Male
CVCL_1F86	U373-MAGI-CXCR4	Cancer cell line	Male
CVCL_1G51	Cf2Th-CXCR4	Spontaneously immortalized cell line	Female
CVCL_1H18	HOS-CXCR4	Cancer cell line	Female
CVCL_1R23	NP-2/CXCR4	Cancer cell line	Male
CVCL_1R29	NP-2/CD4/CXCR4	Cancer cell line	Male
CVCL_B1PP	Abcam HeLa CXCR4 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03995108	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety Study of Mavorixafor in Participants With Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) Syndrome
NCT03005327	PHASE2	COMPLETED	A Dose Determination and Safety Study of X4P-001 (Mavorixafor) in Participants With Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) Syndrome
NCT03087370	Not specified	WITHDRAWN	A Retrospective and Prospective Natural History Study of Patients With WHIM Syndrome