CCL3

Summary

CCL3 (C-C motif chemokine ligand 3, HGNC:10627) is a protein-coding gene on chromosome 17q12, encoding C-C motif chemokine 3 (P10147). Monokine with inflammatory and chemokinetic properties.

This locus represents a small inducible cytokine. The encoded protein, also known as macrophage inflammatory protein 1 alpha, plays a role in inflammatory responses through binding to the receptors CCR1, CCR4 and CCR5. Polymorphisms at this locus may be associated with both resistance and susceptibility to infection by human immunodeficiency virus type 1.

Source: NCBI Gene 6348 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 19 total
• MANE Select transcript: NM_002983

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10627
Approved symbol	CCL3
Name	C-C motif chemokine ligand 3
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	G0S19-1, LD78ALPHA, MIP-1-alpha, LD78, SCI
Ensembl gene	ENSG00000277632
Ensembl biotype	protein_coding
OMIM	182283
Entrez	6348

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 1 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000613922, ENST00000613928, ENST00000614051

RefSeq mRNA: 1 — MANE Select: NM_002983 NM_002983

CCDS: CCDS11307

Canonical transcript exons

ENST00000613396 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 94.14.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6050 / max 87.3958, expressed in 131 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165437	278.9117	583
208148	189.9090	467
165436	0.1778	74
208145	0.0983	46
208136	0.0924	32
208146	0.0900	34
208144	0.0693	27
165435	0.0607	28
208147	0.0164	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow	UBERON:0002371	94.14	gold quality
granulocyte	CL:0000094	93.02	gold quality
spleen	UBERON:0002106	92.23	gold quality
monocyte	CL:0000576	91.19	gold quality
leukocyte	CL:0000738	90.86	gold quality
bone marrow cell	CL:0002092	90.17	gold quality
gall bladder	UBERON:0002110	89.15	gold quality
placenta	UBERON:0001987	87.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.96	gold quality
lymph node	UBERON:0000029	84.15	gold quality
vermiform appendix	UBERON:0001154	83.64	gold quality
blood	UBERON:0000178	81.89	gold quality
omental fat pad	UBERON:0010414	81.55	gold quality
upper lobe of left lung	UBERON:0008952	81.04	gold quality
liver	UBERON:0002107	80.49	gold quality
rectum	UBERON:0001052	79.84	gold quality
smooth muscle tissue	UBERON:0001135	79.50	gold quality
right lobe of liver	UBERON:0001114	78.79	gold quality
duodenum	UBERON:0002114	78.76	gold quality
lung	UBERON:0002048	78.23	gold quality
ascending aorta	UBERON:0001496	75.51	gold quality
adipose tissue	UBERON:0001013	75.19	gold quality
thoracic aorta	UBERON:0001515	75.17	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	74.01	gold quality
cortex of kidney	UBERON:0001225	73.76	gold quality
right coronary artery	UBERON:0001625	73.40	gold quality
left uterine tube	UBERON:0001303	72.93	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.91	gold quality
right lung	UBERON:0002167	72.53	gold quality
left coronary artery	UBERON:0001626	72.01	gold quality

Single-cell (SCXA)

Detected in 30 experiment(s), a significant marker in 30.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	30986.74
E-MTAB-9435	yes	5700.28
E-MTAB-6678	yes	5649.89
E-MTAB-7407	yes	4972.77
E-MTAB-6075	yes	4790.62
E-MTAB-6701	yes	4199.38
E-HCAD-24	yes	3781.93
E-HCAD-8	yes	2776.97
E-MTAB-9067	yes	2018.08
E-MTAB-6505	yes	1587.30
E-CURD-88	yes	1507.51
E-HCAD-4	yes	1056.15
E-ANND-5	yes	792.37
E-MTAB-8894	yes	590.08
E-HCAD-11	yes	467.76

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

6 targets.

Target	Regulation
BGLAP	Repression
ITGAM	Activation
MBP	Activation
SELE	Activation
SP7	Repression
TNF	Activation

Upstream regulators (CollecTRI, top): ATF3, ATF7, BCL6, CEBPA, CEBPB, CEBPG, CREB1, E2F1, EOMES, FOXL2, HEXB, IRF3, IRF4, IRF5, IRF6, IRF7, KAT6A, KAT6B, MEIS1, NFKB1, NFKB, NFKBIA, NR4A1, NR4A2, NR4A3, PPARG, RELA, RUNX1, SPI1, STAT1, TBX21, TREM2

miRNA regulators (miRDB)

12 targeting CCL3, 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-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-7976	95.75	65.67	1186

Literature-anchored findings (GeneRIF, showing 40)

• Inhibition of macrophage inflammatory protein-1 alpha production by Epstein-Barr virus. (PMID:11861262)
• enhances the migration of bone marrow stromal cells (PMID:12186702)
• role in the development of osteolytic lesions in multiple myeloma (PMID:12200385)
• Expression of MIP-1 alpha is induced by stimulation of monocytic cells through Fc gamma receptors and involves activation of CCAAT/enhancer-binding protein beta sites. (PMID:12218153)
• Burned patients seem to be more susceptible to infectious complications when the production of MIP-1 alpha is impaired. (PMID:12370381)
• role of IL-12 and IFN-gamma on inducing inflammatory chemokine (MIP-1alpha) secretion and down-regulating CCR5 expression in human T cells (PMID:12377943)
• After stimulation via high-affinity FcepsilonRI, the transcriptional levels of I-309 (CCL1), MIP-1alpha (CCL3) and MIP-1beta (CCL4) were found among the 10 most increased human and mouse transcripts from approximately 12 000 genes (PMID:12393595)
• Lymphotactin, (MIP)-1alpha, and MIP-1beta chemokines were all rapidly induced by engagement of CD28 and were calcineurin sensitive. (PMID:12393716)
• MIP-1alpha and MIP-1beta show diverging signaling capacities [review] (PMID:12401480)
• The polymorphisms of the MCP-1 and MIP-1A genes do not play a substantial role in genetic predisposition for sarcoidosis or in clinical manifestations of sarcoidosis in this Japanese population. (PMID:12413001)
• may not only mark a subset of patients with a greater risk of having more severe disease but also may play a relevant pathophysiological role in human schistosomiasis mansoni (PMID:12447751)
• Besides its role in development of osteolytic bone destruction, MIP-1 alpha also directly affects cell signaling pathways mediating growth, survival, and migration in MM cells and might play a pivotal role in the pathogenesis of MM. (PMID:12506012)
• AML-1A and AML-1B regulate the expression of this protein in multiple myeloma cells. (PMID:12560229)
• IL-1beta-induced MIP-1alpha and -1beta expression in NT2-N cells (PMID:12603824)
• Cathepsin D specifically cleaves this protein that is expressed in human breast cancer. (PMID:12651610)
• Potential interaction between CCR1 and its ligand, this protein is enduced by endogenously produced interleukin-1 in human hepatomas. (PMID:12651617)
• Transcriptional activation of the MIP-1alpha promoter by RUNX1 and MOZ. (PMID:12771199)
• Therefore, soluble factors such as prostaglandin E(2) released from lung fibroblasts are responsible for the co-culture-induced inhibition of macrophage-derived MIP-1alpha production. (PMID:14680814)
• MIP-1-alpha is substantially regulated upon monocyte contact with various cell wall components from Gran-positive and Gram-negative bacteria. (PMID:14733721)
• Collagen II-reactive T cells in rheumatoid arthritis joints can increase the production of chemokines such as IL-8, MCP-1, and MIP-1 alpha through interaction with synoviocytes. (PMID:15077296)
• lymphocytes of HIV patients display a disrupted capacity to secrete the beta-chemokines MIP-1 alpha and MIP-1 beta, which may constitute a mechanism of immune dysfunction in progressive HIV infection (PMID:15585099)
• produced by neonatal natural killer cells and contributes to suppession of HIV replication (PMID:15588341)
• Role in the development of bronchiolitis associated with influenza and RSV infections in infants and children. (PMID:15602730)
• severe periodontal tissue destruction in Papillon-Lefevre syndrome may be related to excess accumulation of LD78beta and LD78alpha and dysregulation of the microbial-induced inflammatory response in the periodontium (PMID:15728180)
• Involvement of the 3 10 helical-turn motif in chemokine function identifies a novel, functionally essential motif within chemokines. (PMID:16234357)
• Higher amounts of MIP-1alpha, MIP-1beta, and RANTES were detected in plasma of HIV-1-positive individuals, particularly those with concomitant pulmonary tuberculosis, although the increase was not found to be statistically significant. (PMID:16379602)
• HIV p17 was able to reduce MIP-1alpha secretion in IL-15 stimulated monocytes (PMID:16427155)
• Levels of MIP-1alpha are low in plasma and follicular fluid of both menstrual and in vitro fertilization (IVF) cycles. (PMID:16439481)
• High levels of CCL3 are present in synovial fluid of children with juvenile idiopathic arthritis. (PMID:16507178)
• MIP-1 alpha promoter function, gene expression, and protein secretion were each down-regulated following inhibition of FGFR3 signaling. (PMID:16849642)
• findings show that CCL3, CCL4 and CCL5 bind on the Leishmania promastigotes (PMID:17005260)
• MIP-1alpha and other chemokines may constitute a link between the innate immune system and familial Mediterranean fever (PMID:17270460)
• CCL3 concentration was much lower in CSF than in serum of the tickborne encephalitis patients, which argues against its significant role as chemoattractant in this condition. (PMID:17357337)
• found a negative correlation between the tear levels of MIP-1alpha and clinical severity in Cystic fibrosis (CF) patients and a positive correlation between the tear levels of MIP-1alpha and the presence of dry eye findings in CF patients (PMID:17572013)
• brain Alzheimer’s disease-derived microvessels express high levels of MIP-1alpha mRNA and release high levels of MIP-1alpha protein (PMID:17656823)
• Significantly higher expression of CCL3 is associated with tumor metastasis and local host defense in oral squamous cell carcinoma (PMID:17914560)
• CCL2 and CCL3 induce both immediate and delayed skin reactions in atopics and nonatopics, and evoke a similar profile of local T cell/macrophage and granulocyte recruitment (PMID:18070228)
• The strong upregulation of CCL3 and CCL4 implicates these chemokines in the etiology and pathogenesis of TLE. (PMID:18076643)
• TNF-alpha unveils a previously unknown capacity of neutrophils to migrate to CCL3 through the intervention of Mac-1. (PMID:18164590)
• Plasma soluble CD40 ligand and stimulated MIP-1alpha production were both reduced (p < or = 0.05) by systemic beta-adrenergic stimulation. (PMID:18196935)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccl35.2	ENSDARG00000070378
danio_rerio	ccl35.1	ENSDARG00000103466
mus_musculus	Ccl3	ENSMUSG00000000982
rattus_norvegicus	Ccl3	ENSRNOG00000011205

Paralogs (26): CX3CL1 (ENSG00000006210), CCL26 (ENSG00000006606), CCL22 (ENSG00000102962), CCL17 (ENSG00000102970), CCL24 (ENSG00000106178), CCL7 (ENSG00000108688), CCL2 (ENSG00000108691), CCL8 (ENSG00000108700), CCL1 (ENSG00000108702), CCL20 (ENSG00000115009), CCL25 (ENSG00000131142), CCL21 (ENSG00000137077), XCL1 (ENSG00000143184), XCL2 (ENSG00000143185), CCL11 (ENSG00000172156), CCL19 (ENSG00000172724), CCL13 (ENSG00000181374), CCL5 (ENSG00000271503), CCL23 (ENSG00000274736), CCL16 (ENSG00000275152), CCL4 (ENSG00000275302), CCL18 (ENSG00000275385), CCL15 (ENSG00000275718), CCL4L2 (ENSG00000276070), CCL3L3 (ENSG00000276085), CCL14 (ENSG00000276409)

Protein

Protein identifiers

C-C motif chemokine 3 — P10147 (reviewed: P10147)

Alternative names: G0/G1 switch regulatory protein 19-1, Macrophage inflammatory protein 1-alpha, PAT 464.1, SIS-beta, Small-inducible cytokine A3, Tonsillar lymphocyte LD78 alpha protein

All UniProt accessions (2): P10147, A0N0R1

UniProt curated annotations — full annotation on UniProt →

Function. Monokine with inflammatory and chemokinetic properties. Binds to CCR1, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-alpha induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV).

Subunit / interactions. Self-associates. Also heterodimer of MIP-1-alpha(4-69) and MIP-1-beta(3-69). Interacts with CCR1.

Subcellular location. Secreted.

Post-translational modifications. N-terminal processed form LD78-alpha(4-69) is produced by proteolytic cleavage after secretion from HTLV1-transformed T-cells.

Induction. By TPA or PHA (TPA = 12-O-tetradecanoyl phorbol-13 acetate (tumor promoter); PHA = phytohemagglutinin (T-cell mitogen)).

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

RefSeq proteins (1): NP_002974* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00048

UniProt features (24 total): strand 7, mutagenesis site 5, helix 3, site 3, chain 2, disulfide bond 2, signal peptide 1, sequence variant 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
3FPU	X-RAY DIFFRACTION	1.76
2X6G	X-RAY DIFFRACTION	2.18
5COR	X-RAY DIFFRACTION	2.55
4RA8	X-RAY DIFFRACTION	2.6
7F1T	X-RAY DIFFRACTION	2.6
2X69	X-RAY DIFFRACTION	2.65
3KBX	X-RAY DIFFRACTION	2.65
4ZKB	X-RAY DIFFRACTION	2.9
7F1Q	ELECTRON MICROSCOPY	2.9
3H44	X-RAY DIFFRACTION	3
5D65	X-RAY DIFFRACTION	3.1
1B50	SOLUTION NMR
1B53	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10147-F1	89.58	0.68

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 (3): 40 (involved in gag binding); 68 (involved in gag binding); 70 (involved in gag binding)

Disulfide bonds (2): 33–57, 34–73

Mutagenesis-validated functional residues (5):

Position	Phenotype
49	reduces self-association; in bb-10010: improved pharmaceutical properties.
68	strongly reduces heparin binding.
70	reduces heparin binding.
89	reduces self-association.
40	slightly reduces heparin binding.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-6783783	Interleukin-10 signaling
R-HSA-9942503	Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-168256	Immune System
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-449147	Signaling by Interleukins
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 468 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_REGULATION_OF_CELL_ACTIVATION, MODULE_92, FUNG_IL2_SIGNALING_2, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_BEHAVIOR, GOBP_POSITIVE_REGULATION_OF_MACROPHAGE_ACTIVATION, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, MCLACHLAN_DENTAL_CARIES_UP, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, MODULE_169

GO Biological Process (54): MAPK cascade (GO:0000165), osteoblast differentiation (GO:0001649), cell activation (GO:0001775), monocyte chemotaxis (GO:0002548), calcium ion transport (GO:0006816), intracellular calcium ion homeostasis (GO:0006874), exocytosis (GO:0006887), chemotaxis (GO:0006935), inflammatory response (GO:0006954), cytoskeleton organization (GO:0007010), cell-cell signaling (GO:0007267), regulation of cell shape (GO:0008360), response to toxic substance (GO:0009636), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), T cell chemotaxis (GO:0010818), release of sequestered calcium ion into cytosol by sarcoplasmic reticulum (GO:0014808), calcium-mediated signaling (GO:0019722), signaling (GO:0023052), positive regulation of cell migration (GO:0030335), negative regulation of bone mineralization (GO:0030502), neutrophil chemotaxis (GO:0030593), positive regulation of interleukin-1 beta production (GO:0032731), positive regulation of tumor necrosis factor production (GO:0032760), eosinophil degranulation (GO:0043308), positive regulation of neuron apoptotic process (GO:0043525), astrocyte cell migration (GO:0043615), host-mediated suppression of viral transcription (GO:0043922), negative regulation of osteoclast differentiation (GO:0045671), eosinophil chemotaxis (GO:0048245), macrophage chemotaxis (GO:0048246), lymphocyte chemotaxis (GO:0048247), positive regulation of inflammatory response (GO:0050729), regulation of behavior (GO:0050795), positive regulation of calcium-mediated signaling (GO:0050850), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of calcium ion transport (GO:0051928), regulation of sensory perception of pain (GO:0051930), cell chemotaxis (GO:0060326), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844)

GO Molecular Function (11): protein kinase activity (GO:0004672), chemokine activity (GO:0008009), phospholipase activator activity (GO:0016004), kinase activity (GO:0016301), CCR1 chemokine receptor binding (GO:0031726), CCR5 chemokine receptor binding (GO:0031730), chemoattractant activity (GO:0042056), identical protein binding (GO:0042802), CCR chemokine receptor binding (GO:0048020), cytokine activity (GO:0005125), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Peptide ligand-binding receptors	1
Signaling by Interleukins	1
Differentiation of T cells	1
Immune System	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Cytokine Signaling in Immune system	1
Signaling by GPCR	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular signaling cassette	2
response to chemical	2
gene expression	2
regulation of gene expression	2
chemokine receptor binding	2
CCR chemokine receptor binding	2
receptor ligand activity	2
ossification	1
cell differentiation	1
cellular process	1
multicellular organismal process	1
leukocyte chemotaxis	1
mononuclear cell migration	1
myeloid leukocyte migration	1
metal ion transport	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
taxis	1
defense response	1
organelle organization	1
cell communication	1
signaling	1
regulation of cell morphogenesis	1
regulation of biological quality	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
lymphocyte chemotaxis	1
T cell migration	1
sarcoplasmic reticulum calcium ion transport	1
release of sequestered calcium ion into cytosol by endoplasmic reticulum	1
regulation of biological process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1

Protein interactions and networks

STRING

3194 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCL3	CCR5	P51681	999
CCL3	CCR1	P32246	998
CCL3	CCR2	P41597	997
CCL3	CCR3	P51677	996
CCL3	CXCR3	P49682	992
CCL3	CXCR4	P30991	979
CCL3	ACKR2	O00590	967
CCL3	CXCR2	P25025	955
CCL3	CXCR1	P25024	945
CCL3	IL10	P22301	945
CCL3	CCL4	P13236	943
CCL3	CCRL2	O00421	942
CCL3	CCL20	P78556	939
CCL3	CXCL8	P10145	932
CCL3	CCR6	P51684	927

IntAct

16 interactions, top by confidence:

A	B	Type	Score
CCL3	CCL3	psi-mi:“MI:0407”(direct interaction)	0.620
IDE	CCL3	psi-mi:“MI:0407”(direct interaction)	0.620
IDE	CCL3	psi-mi:“MI:0194”(cleavage reaction)	0.620
CCL3	IDE	psi-mi:“MI:0407”(direct interaction)	0.620
	CCL3	psi-mi:“MI:0407”(direct interaction)	0.560
CCL3	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
CCL3	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
CCL3	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
CCL3	UBQLN1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (171): CCL3 (Affinity Capture-RNA), CCL3 (Two-hybrid), CCL3 (Two-hybrid), CCR5 (Reconstituted Complex), CCL3 (Reconstituted Complex), CCL4 (Affinity Capture-MS), CCL3 (Affinity Capture-MS), EMILIN3 (Affinity Capture-MS), B3GALTL (Affinity Capture-MS), B4GALT4 (Affinity Capture-MS), B4GALT3 (Affinity Capture-MS), BCHE (Affinity Capture-MS), SLIT2 (Affinity Capture-MS), LARP4 (Affinity Capture-MS), CRISPLD1 (Affinity Capture-MS)

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

Diamond homologs: F5HET8, O00175, O00585, O00626, O55145, O88430, O97919, P10147, P10148, P10855, P13236, P13500, P13501, P14097, P14844, P16619, P27784, P28291, P28292, P30882, P42831, P46632, P47993, P49873, P50229, P50230, P50231, P51670, P51671, P52203, P55773, P55774, P61274, P61275, P78423, P80075, P80098, P80343, P82943, P97272

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
maraviroc	down-regulates	CCL3	“chemical inhibition”
KAT6A	“up-regulates quantity by expression”	CCL3	“transcriptional regulation”
RUNX1	“up-regulates quantity by expression”	CCL3	“transcriptional regulation”
CCL3	up-regulates	CCR1	binding
CCL3	“up-regulates activity”	CCR1	binding
CCL3	“up-regulates activity”	CCR2	binding
CCL3	“up-regulates activity”	CCR5	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

132 predictions. Top by Δscore:

Variant	Effect	Δscore
17:36088758:GGAAG:G	acceptor_gain	1.0000
17:36088759:GAAG:G	acceptor_gain	1.0000
17:36088761:AG:A	acceptor_gain	1.0000
17:36088763:C:CC	acceptor_gain	1.0000
17:36088763:CT:C	acceptor_loss	1.0000
17:36089178:CTT:C	donor_loss	1.0000
17:36089181:A:AC	donor_gain	1.0000
17:36089182:C:CT	donor_gain	1.0000
17:36089182:CA:C	donor_gain	1.0000
17:36089182:CATGA:C	donor_gain	1.0000
17:36089184:TGAC:T	donor_gain	1.0000
17:36089293:AGCAA:A	acceptor_gain	1.0000
17:36089294:GCAA:G	acceptor_gain	1.0000
17:36089295:CAA:C	acceptor_gain	1.0000
17:36089295:CAAC:C	acceptor_gain	1.0000
17:36089296:AA:A	acceptor_gain	1.0000
17:36089297:ACTGT:A	acceptor_loss	1.0000
17:36089298:C:CC	acceptor_gain	1.0000
17:36089300:G:C	acceptor_gain	1.0000
17:36088760:AAG:A	acceptor_gain	0.9900
17:36088765:G:C	acceptor_gain	0.9900
17:36089182:CAT:C	donor_gain	0.9900
17:36089182:CATG:C	donor_gain	0.9900
17:36089300:G:GC	acceptor_gain	0.9900
17:36089982:TCA:T	donor_loss	0.9900
17:36089983:CAC:C	donor_loss	0.9900
17:36089984:A:AC	donor_gain	0.9900
17:36089984:AC:A	donor_loss	0.9900
17:36089985:C:CC	donor_gain	0.9900
17:36088765:G:GC	acceptor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000276697 (17:36089061 G>A,C,T), RS1001267821 (17:36088048 G>C), RS1002466957 (17:36092101 G>C,T), RS1002867209 (17:36091891 G>A), RS1004867390 (17:36090686 C>T), RS1005422327 (17:36091000 C>G,T), RS1008877297 (17:36087780 A>C), RS1008995758 (17:36091800 C>T), RS1010294883 (17:36088025 C>T), RS1011104207 (17:36091840 G>C), RS1011982823 (17:36090656 C>T), RS1012466913 (17:36090346 G>A), RS1013399921 (17:36089556 G>A), RS1013986556 (17:36088578 C>T), RS1014472741 (17:36088291 A>C)

Disease associations

OMIM: gene MIM:182283 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005951_15	Body mass index	3.000000e-13
GCST006585_1580	Blood protein levels	3.000000e-73
GCST009731_59	Blood protein levels in cardiovascular risk	8.000000e-35

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

Binding affinities (BindingDB)

5 measured of 7 human assays (7 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CC-220 (Compound 6)	IC50	28 nM	US-9694015: Methods for the treatment of locally advanced breast cancer
3-(4-((4-(morpholinomethyl)benzyl)-oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione	IC50	190 nM	US-9694015: Methods for the treatment of locally advanced breast cancer
19171-19-8	IC50	230 nM	US-9694015: Methods for the treatment of locally advanced breast cancer
3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione	IC50	300 nM	US-9694015: Methods for the treatment of locally advanced breast cancer
(R)-3-(4-((4-(morpholinomethyl)benzyl)-oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione	IC50	450 nM	US-9694015: Methods for the treatment of locally advanced breast cancer

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	increases reaction, decreases expression, affects response to substance, decreases reaction, increases secretion (+2 more)	16
Resveratrol	affects cotreatment, decreases expression, decreases reaction, increases expression, affects localization	6
nickel sulfate	affects expression, increases expression	4
Tetradecanoylphorbol Acetate	increases reaction, affects cotreatment, decreases reaction, increases expression, increases secretion	4
ferric oxide	decreases reaction, increases secretion, increases expression	3
Tretinoin	increases expression	3
Ionomycin	affects cotreatment, decreases reaction, increases expression, increases secretion	3
stearic acid	increases expression	2
perfluorooctane sulfonic acid	increases expression	2
lipopolysaccharide, E. coli O26-B6	increases expression, decreases reaction	2
lipopolysaccharide, E coli O55-B5	decreases reaction, increases secretion, increases reaction	2
Asbestos	increases expression	2
Vehicle Emissions	decreases expression, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Dexamethasone	decreases reaction, increases secretion, increases expression	2
Dinitrochlorobenzene	increases expression	2
Eugenol	increases expression, increases secretion	2
Isoproterenol	decreases reaction, increases expression	2
Methotrexate	decreases expression, decreases reaction	2
Oxygen	increases reaction, affects reaction, increases expression	2
Prednisolone	increases expression, decreases reaction, increases secretion	2
Dinoprostone	decreases reaction, increases secretion, increases reaction, decreases expression	2
Ritonavir	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases expression	2
coagulin-L	decreases reaction, increases expression	1
coralyne	decreases expression	1
TL8-506	affects cotreatment, increases expression, increases secretion	1
alexidine	decreases expression	1
7-ketocholesterol	decreases reaction, increases expression	1
2-anisidine	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1AA	Abcam THP-1 CCL3 KO	Cancer cell line	Male
CVCL_B8CJ	Abcam HCT 116 CCL3 KO	Cancer cell line	Male
CVCL_B9EQ	Abcam A-549 CCL3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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