CCL4L1

Summary

CCL4L1 (C-C motif chemokine ligand 4 like 1, HGNC:10631) is a protein-coding gene on chromosome 17q12 alternate reference locus, encoding C-C motif chemokine 4-like (Q8NHW4). Chemokine that induces chemotaxis of cells expressing CCR5 or CCR1.

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 family member is similar to the chemokine (C-C motif) ligand 4 product, which inhibits HIV entry by binding to the cellular receptor CCR5. The copy number of this gene varies among individuals, where most individuals have one to five copies. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 388372 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_207007

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10631
Approved symbol	CCL4L1
Name	C-C motif chemokine ligand 4 like 1
Location	17q12 alternate reference locus
Locus type	gene with protein product
Status	Approved
Aliases	AT744.2, LAG-1
Ensembl gene	ENSG00000282604
OMIM	603782
Entrez	388372

Gene structure

Transcript identifiers

Ensembl transcripts: 0

RefSeq mRNA: 1 — MANE Select: NM_207007 NM_207007

Canonical transcript exons

ENST00000634014 — 0 exons

Expression profiles

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6411 / max 98.2444, expressed in 134 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160410	0.3887	97
160411	0.1930	60
208154	0.0594	25

Top tissues by expression

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

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-29	yes	54121.34
E-MTAB-9435	yes	17223.80
E-MTAB-7407	yes	4917.37
E-CURD-46	yes	2662.52
E-MTAB-8142	yes	1598.84
E-MTAB-8381	yes	1290.57
E-HCAD-1	yes	1214.35
E-MTAB-9467	yes	1182.09
E-MTAB-6075	yes	1161.34
E-HCAD-4	yes	1065.43
E-MTAB-8221	yes	819.27
E-MTAB-8322	yes	762.91
E-MTAB-8207	yes	295.32
E-MTAB-8530	yes	180.60
E-MTAB-9906	yes	112.61

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• multiple copies of CCL3L1 and CCL4L1 present in a single diploid genome are the result of segmental duplication at chromosome 17q12 (PMID:15028295)
• CCL4L1 allele frequency is higher in severe psoriasis, whereas CCL4L2 is more frequent in patients with a milder disease. (PMID:21614014)
• PCR results show that lower copy numbers of CCL4L1 are observed in the Caucasian population nd higher copy numbers are observed in the Black population of South Africa. (PMID:24727646)
• identified 13 ADCC-activated genes. Six gene expression assays including 8 of the 13 genes (CCL3, CCL4/CCL4L1/CCL4L2, CD160, IFNG, NR4A3 and XCL1/XCL2) were analyzed in 127 kidney biopsies (PMID:25449536)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

C-C motif chemokine 4-like — Q8NHW4 (reviewed: Q8NHW4)

Alternative names: Lymphocyte activation gene 1 protein, Macrophage inflammatory protein 1-beta, Monocyte adherence-induced protein 5-alpha, Small-inducible cytokine A4-like

All UniProt accessions (2): Q8NHW4, A0A0J9YWH4

UniProt curated annotations — full annotation on UniProt →

Function. Chemokine that induces chemotaxis of cells expressing CCR5 or CCR1. Inhibits HIV replication in peripheral blood monocytes that express CCR5.

Subunit / interactions. Interacts with CCR5.

Subcellular location. Secreted.

Tissue specificity. Detected in B-cells.

Polymorphism. The copy number of the CC4L1 gene varies among individuals; most individuals have 1 to 6 copies in the diploid genome.

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

Isoforms (10)

UniProt ID	Names	Canonical?
Q8NHW4-1	1	yes
Q8NHW4-2	2, CCL4L2
Q8NHW4-3	3, CC4L2d
Q8NHW4-4	4, CC4L2f
Q8NHW4-5	5, CC4L2b1, CC4L2b2
Q8NHW4-6	6, CC4L2e
Q8NHW4-7	7, CC4L2d2
Q8NHW4-8	8, CC4L1d2
Q8NHW4-9	9, CC4L2bd2
Q8NHW4-10	10, CC44L2c

RefSeq proteins (1): NP_996890* (*=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 (14 total): splice variant 9, disulfide bond 2, signal peptide 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NHW4-F1	89.93	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.

Disulfide bonds (2): 34–58, 35–74

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-418594	G alpha (i) signalling events
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling

MSigDB gene sets: 0 (showing top):

GO Biological Process (9): inflammatory response (GO:0006954), positive regulation of cell migration (GO:0030335), eosinophil chemotaxis (GO:0048245), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), chemokine-mediated signaling pathway (GO:0070098), chemotaxis (GO:0006935), immune response (GO:0006955), signal transduction (GO:0007165), cell chemotaxis (GO:0060326)

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): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
GPCR downstream signalling	1
Signal Transduction	1
Signaling by GPCR	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell migration	2
chemokine receptor binding	2
defense response	1
regulation of cell migration	1
positive regulation of cell motility	1
granulocyte chemotaxis	1
eosinophil migration	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
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
chemotaxis	1
cellular response to chemical stimulus	1
cytokine activity	1
cell chemotaxis	1
receptor ligand activity	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

104 interactions, top by confidence:

A	B	Type	Score
SLC30A2	CCL4L1	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	SLC30A2	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	ERVFRD-1	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	COMT	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	SLC7A1	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	SSMEM1	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	AQP6	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	SGPL1	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	GPR42	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	CATSPER4	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	TMEM51	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	MFSD14B	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	ITM2C	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
EBP	CCL4L1	psi-mi:“MI:0915”(physical association)	0.560
COQ9	CCL4L1	psi-mi:“MI:0915”(physical association)	0.560
CATSPER4	CCL4L1	psi-mi:“MI:0915”(physical association)	0.560
CPLX4	CCL4L1	psi-mi:“MI:0915”(physical association)	0.560
JAGN1	CCL4L1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (57): CCL4L2 (Two-hybrid), CCL4L2 (Two-hybrid), CCL4L2 (Two-hybrid), CCL4L2 (Two-hybrid), CCL4L2 (Two-hybrid), CCL4L2 (Two-hybrid), CCL4L2 (Two-hybrid), CCL4L2 (Two-hybrid), CCL4L2 (Two-hybrid), CCL4L2 (Two-hybrid), CCL4L2 (Two-hybrid), CCL4L2 (Two-hybrid), CCL4L2 (Two-hybrid), CCL4L2 (Two-hybrid), CCL4L2 (Two-hybrid)

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

1 interactions.

A	Effect	B	Mechanism
maraviroc	down-regulates	CCL4L1	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 117 via entrez): RS1024303240 (17:36213214 G>A,C), RS1159320416 (17:36213159 G>T), RS1171843648 (17:36213172 A>G), RS1172454476 (17:36213298 C>A), RS1175873508 (17:36213277 A>C), RS1177284242 (17:36213237 A>G), RS1186628044 (17:36213179 T>C), RS1188896844 (17:36213310 C>T), RS1204812035 (17:36213325 G>T), RS1215745010 (17:36213284 T>A), RS1218170262 (17:36213182 A>C,G), RS1219877050 (17:36213282 A>C,G), RS1220031143 (17:36213332 G>A,C), RS1220124694 (17:36213194 A>T), RS1226693738 (17:36213226 A>G)

Disease associations

OMIM: gene MIM:603782 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004433_17	Macrophage inflammatory protein 1b levels	2.000000e-173
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

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	increases reaction, affects binding	1
abrine	increases expression	1
gardiquimod	increases expression, decreases reaction	1
Benzo(a)pyrene	increases methylation	1
Diuron	decreases expression	1
Zinc	decreases expression	1
beta-Naphthoflavone	decreases expression	1
Protein Kinase Inhibitors	decreases reaction, increases expression	1

Clinical trials (associated diseases)

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