CCL3L3

Summary

CCL3L3 (C-C motif chemokine ligand 3 like 3, HGNC:30554) is a protein-coding gene on chromosome 17q12, encoding C-C motif chemokine 3-like 1 (P16619). Chemotactic for lymphocytes and monocytes.

This gene is one of several cytokine genes that are clustered on the q-arm of chromosome 17. Cytokines are a family of secreted proteins that function in inflammatory and immunoregulatory processes. The protein encoded by this gene binds to several chemokine receptors, including chemokine binding protein 2 and chemokine (C-C motif) receptor 5 (CCR5). CCR5 is a co-receptor for HIV, and binding of this protein to CCR5 inhibits HIV entry. The copy number of this gene varies among individuals, where most individuals have one to six copies, and a minority of individuals have zero or more than six copies. There are conflicting reports about copy number variation of this gene and its correlation to disease susceptibility.

Source: NCBI Gene 414062 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 11 total
• MANE Select transcript: NM_001001437

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30554
Approved symbol	CCL3L3
Name	C-C motif chemokine ligand 3 like 3
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	MGC12815
Ensembl gene	ENSG00000276085
Ensembl biotype	protein_coding
OMIM	609468
Entrez	414062

Gene structure

Transcript identifiers

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

ENST00000612839, ENST00000616702, ENST00000619989

RefSeq mRNA: 1 — MANE Select: NM_001001437 NM_001001437

CCDS: CCDS32626

Canonical transcript exons

ENST00000612067 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 90.75.

FANTOM5 (CAGE): breadth broad, TPM avg 189.9090 / max 19018.7799, expressed in 467 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
208148	189.9090	467

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	90.75	gold quality
monocyte	CL:0000576	85.84	gold quality
bone marrow cell	CL:0002092	85.75	gold quality
leukocyte	CL:0000738	85.66	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.89	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.99	gold quality
lymph node	UBERON:0000029	78.60	gold quality
vermiform appendix	UBERON:0001154	77.02	gold quality
blood	UBERON:0000178	76.99	gold quality
granulocyte	CL:0000094	75.88	gold quality
spleen	UBERON:0002106	75.54	gold quality
gall bladder	UBERON:0002110	74.10	gold quality
superior frontal gyrus	UBERON:0002661	71.65	gold quality
mucosa of transverse colon	UBERON:0004991	69.49	gold quality
placenta	UBERON:0001987	68.53	gold quality
prefrontal cortex	UBERON:0000451	68.01	gold quality
duodenum	UBERON:0002114	66.78	gold quality
smooth muscle tissue	UBERON:0001135	66.76	gold quality
rectum	UBERON:0001052	66.66	gold quality
right ovary	UBERON:0002118	66.44	gold quality
frontal cortex	UBERON:0001870	66.07	gold quality
ovary	UBERON:0000992	64.48	gold quality
liver	UBERON:0002107	64.44	gold quality
primary visual cortex	UBERON:0002436	64.29	gold quality
left ovary	UBERON:0002119	63.58	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	63.33	gold quality
right lobe of liver	UBERON:0001114	63.28	gold quality
small intestine Peyer’s patch	UBERON:0003454	62.93	gold quality
small intestine	UBERON:0002108	62.86	gold quality
right frontal lobe	UBERON:0002810	62.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	2147.16
E-ANND-3	yes	11.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting CCL3L3, 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-5692A	100.00	74.40	6850
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4458	99.96	71.64	1650
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-182-5P	99.87	74.03	2589
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4687-3P	99.48	66.41	968
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-603	98.58	68.28	1603
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-6773-5P	97.04	64.30	595
HSA-MIR-7847-3P	96.63	64.58	952
HSA-MIR-6724-5P	96.41	63.11	507
HSA-MIR-7976	95.75	65.67	1186

Literature-anchored findings (GeneRIF, showing 1)

• 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)

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), CCL14 (ENSG00000276409), CCL3 (ENSG00000277632)

Protein

Protein identifiers

C-C motif chemokine 3-like 1 — P16619 (reviewed: P16619)

Alternative names: G0/G1 switch regulatory protein 19-2, LD78-beta(1-70), PAT 464.2, Small-inducible cytokine A3-like 1, Tonsillar lymphocyte LD78 beta protein

All UniProt accessions (1): P16619

UniProt curated annotations — full annotation on UniProt →

Function. Chemotactic for lymphocytes and monocytes. Is a ligand for CCR1, CCR3 and CCR5. Is an inhibitor of HIV-1-infection. The processed form LD78-beta(3-70) shows a 20-fold to 30-fold higher chemotactic activity and is a very potent inhibitor of HIV-1-infection. LD78-beta(3-70) is also a ligand for CCR1, CCR3 and CCR5.

Subcellular location. Secreted.

Post-translational modifications. The N-terminal processed forms LD78-beta(3-70) and LD78-beta(5-70) are produced by proteolytic cleavage after secretion from peripheral blood monocytes. The cleavage to yield LD78-beta(3-70) is probably achieved by DPP4.

Polymorphism. The copy number of the CCL3L1 gene varies among individuals; most individuals have 1-6 copies in the diploid genome, although rare individuals have zero or more than 6 copies.

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

RefSeq proteins (1): NP_001001437* (*=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 (8 total): chain 3, disulfide bond 2, signal peptide 1, site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16619-F1	90.15	0.67

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 (1): 25–26 (cleavage; by dpp4)

Disulfide bonds (2): 34–58, 35–74

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-6783783	Interleukin-10 signaling

MSigDB gene sets: 66 (showing top): GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_CELL_CHEMOTAXIS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_TAXIS, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_HUMORAL_IMMUNE_RESPONSE, GOMF_CHEMOKINE_ACTIVITY, GOMF_CYTOKINE_ACTIVITY, GOMF_G_PROTEIN_COUPLED_RECEPTOR_BINDING, GOMF_SIGNALING_RECEPTOR_BINDING, GEORGES_TARGETS_OF_MIR192_AND_MIR215, REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS

GO Biological Process (8): inflammatory response (GO:0006954), negative regulation of cell population proliferation (GO:0008285), positive regulation of cell migration (GO:0030335), cell chemotaxis (GO:0060326), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), chemokine-mediated signaling pathway (GO:0070098), chemotaxis (GO:0006935), immune response (GO:0006955)

GO Molecular Function (4): chemokine activity (GO:0008009), CCR chemokine receptor binding (GO:0048020), cytokine activity (GO:0005125), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Peptide ligand-binding receptors	1
Signaling by Interleukins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell migration	2
chemokine receptor binding	2
defense response	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
regulation of cell migration	1
positive regulation of cell motility	1
chemotaxis	1
cellular response to chemical stimulus	1
antimicrobial humoral response	1
G protein-coupled receptor signaling pathway	1
cytokine-mediated signaling pathway	1
cellular response to chemokine	1
response to chemical	1
taxis	1
immune system process	1
response to stimulus	1
cytokine activity	1
cell chemotaxis	1
receptor ligand activity	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1552 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCL3L3	CCR5	P51681	998
CCL3L3	CCR1	P32246	975
CCL3L3	CCR3	P51677	971
CCL3L3	CCR2	P41597	804
CCL3L3	ACKR2	O00590	774
CCL3L3	CXCL8	P10145	706
CCL3L3	CCL5	P13501	694
CCL3L3	IL1B	P01584	668
CCL3L3	TNF	P01375	668
CCL3L3	CX3CR1	P49238	643
CCL3L3	CCL20	P78556	638
CCL3L3	CCR7	P32248	629
CCL3L3	CXCL1	P09341	622
CCL3L3	CXCL10	P02778	617
CCL3L3	CD4	P01730	614

IntAct

14 interactions, top by confidence:

A	B	Type	Score
CCL3L1	SLC41A3	psi-mi:“MI:0915”(physical association)	0.560
CCL3L1	SGTB	psi-mi:“MI:0915”(physical association)	0.560
CCL3L1	MGST2	psi-mi:“MI:0915”(physical association)	0.560
CCL3L1	TMEM179B	psi-mi:“MI:0915”(physical association)	0.560
CCL3L1	QSOX1	psi-mi:“MI:0914”(association)	0.350
CCL3L1	SLC41A3	psi-mi:“MI:0915”(physical association)	0.000
CCL3L1	SGTB	psi-mi:“MI:0915”(physical association)	0.000
CCL3L1	TMEM179B	psi-mi:“MI:0915”(physical association)	0.000
CCL3L1	MGST2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (40): CCL3L3 (Two-hybrid), CCL3L3 (Two-hybrid), CCL3L3 (Two-hybrid), CCL3L3 (Two-hybrid), CCR5 (Reconstituted Complex), CTSV (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), IDE (Affinity Capture-MS), ARSB (Affinity Capture-MS), PCOLCE2 (Affinity Capture-MS), H6PD (Affinity Capture-MS), SEMA3C (Affinity Capture-MS), TLN2 (Affinity Capture-MS), ADAMTS1 (Affinity Capture-MS), SULF2 (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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

253 predictions. Top by Δscore:

Variant	Effect	Δscore
17:36195372:GGAAG:G	acceptor_gain	1.0000
17:36195375:AG:A	acceptor_gain	1.0000
17:36195377:C:CC	acceptor_gain	1.0000
17:36195795:TAC:T	donor_loss	1.0000
17:36195796:A:AC	donor_gain	1.0000
17:36195797:C:A	donor_loss	1.0000
17:36195797:C:CG	donor_gain	1.0000
17:36195797:C:CT	donor_gain	1.0000
17:36195797:CA:C	donor_gain	1.0000
17:36195797:CAT:C	donor_gain	1.0000
17:36195797:CATG:C	donor_gain	1.0000
17:36195797:CATGA:C	donor_gain	1.0000
17:36195908:AGCAA:A	acceptor_gain	1.0000
17:36195909:GCAA:G	acceptor_gain	1.0000
17:36195910:CAA:C	acceptor_gain	1.0000
17:36195910:CAAC:C	acceptor_gain	1.0000
17:36195911:AA:A	acceptor_gain	1.0000
17:36195913:C:CC	acceptor_gain	1.0000
17:36195297:G:C	donor_gain	0.9900
17:36195373:GAAG:G	acceptor_gain	0.9900
17:36195374:AAG:A	acceptor_gain	0.9900
17:36195376:GCT:G	acceptor_loss	0.9900
17:36195377:C:CA	acceptor_loss	0.9900
17:36195379:G:C	acceptor_gain	0.9900
17:36195791:CACT:C	donor_loss	0.9900
17:36195791:CACTT:C	donor_gain	0.9900
17:36195792:ACTT:A	donor_gain	0.9900
17:36195793:CTT:C	donor_gain	0.9900
17:36195794:TTA:T	donor_gain	0.9900
17:36195795:TACA:T	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1010790555 (17:36197455 G>A,C), RS1022174028 (17:36197770 A>G), RS113266921 (17:36198514 T>A,C), RS1156645499 (17:36196598 G>A), RS1156678616 (17:36195462 G>C), RS1158869375 (17:36197081 C>G,T), RS1159080511 (17:36194624 A>G), RS1159621745 (17:36197065 T>C), RS1159880558 (17:36195333 C>T), RS1160043729 (17:36195001 C>T), RS1160358441 (17:36194462 G>T), RS1160558457 (17:36198352 A>G), RS1160986448 (17:36195927 G>A,C), RS1161455255 (17:36195489 C>G,T), RS1161508516 (17:36196146 T>C)

Disease associations

OMIM: gene MIM:609468 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_15	Body mass index	3.000000e-13

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)

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
15-acetyldeoxynivalenol	increases expression	1
Pioglitazone	decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects binding, decreases expression	1
Lipopolysaccharides	affects response to substance, affects cotreatment, increases expression	1
Malathion	increases expression	1
Zinc	decreases expression	1
Aflatoxin B1	decreases methylation	1
beta-Naphthoflavone	decreases expression	1

Clinical trials (associated diseases)

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