CKLF

Summary

CKLF (chemokine like factor, HGNC:13253) is a protein-coding gene on chromosome 16q21, encoding Chemokine-like factor (Q9UBR5). May play an important role in inflammation and regeneration of skeletal muscle.

The product of this gene is a cytokine. Cytokines are small proteins that have an essential role in the immune and inflammatory responses. This gene is one of several chemokine-like factor genes located in a cluster on chromosome 16. The protein encoded by this gene is a potent chemoattractant for neutrophils, monocytes and lymphocytes. It also can stimulate the proliferation of skeletal muscle cells. This protein may play important roles in inflammation and in the regeneration of skeletal muscle. Alternatively spliced transcript variants encoding different isoforms have been identified. Naturally occurring read-through transcription occurs between this locus and the neighboring locus CMTM1 (CKLF-like MARVEL transmembrane domain containing 1).

Source: NCBI Gene 51192 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_016951

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13253
Approved symbol	CKLF
Name	chemokine like factor
Location	16q21
Locus type	gene with protein product
Status	Approved
Aliases	UCK-1, CKLF3, CKLF4, HSPC224, C32
Ensembl gene	ENSG00000217555
Ensembl biotype	protein_coding
OMIM	616074
Entrez	51192

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000264001, ENST00000345436, ENST00000351137, ENST00000362093, ENST00000417030, ENST00000526149, ENST00000534692, ENST00000563092

RefSeq mRNA: 5 — MANE Select: NM_016951 NM_001040138, NM_016326, NM_016951, NM_181640, NM_181641

CCDS: CCDS10806, CCDS10807, CCDS10808, CCDS10809, CCDS45502

Canonical transcript exons

ENST00000264001 — 4 exons

Exon	Start	End
ENSE00000000343	66565886	66566068
ENSE00001104113	66558190	66558348
ENSE00001853920	66552576	66552793
ENSE00003710527	66563122	66563217

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 98.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.1365 / max 649.3255, expressed in 1822 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154514	39.1365	1822

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.89	gold quality
leukocyte	CL:0000738	98.82	gold quality
granulocyte	CL:0000094	97.79	gold quality
blood	UBERON:0000178	97.06	gold quality
vermiform appendix	UBERON:0001154	96.55	gold quality
lymph node	UBERON:0000029	95.94	gold quality
spleen	UBERON:0002106	95.41	gold quality
left testis	UBERON:0004533	95.31	gold quality
right testis	UBERON:0004534	95.22	gold quality
islet of Langerhans	UBERON:0000006	95.05	gold quality
rectum	UBERON:0001052	95.02	gold quality
gall bladder	UBERON:0002110	94.96	gold quality
testis	UBERON:0000473	94.90	gold quality
bone marrow	UBERON:0002371	94.21	gold quality
bone marrow cell	CL:0002092	94.17	gold quality
mucosa of transverse colon	UBERON:0004991	93.92	gold quality
smooth muscle tissue	UBERON:0001135	93.67	gold quality
right lung	UBERON:0002167	93.30	gold quality
ventricular zone	UBERON:0003053	93.16	gold quality
stromal cell of endometrium	CL:0002255	92.75	gold quality
duodenum	UBERON:0002114	92.67	gold quality
fallopian tube	UBERON:0003889	92.00	gold quality
upper lobe of left lung	UBERON:0008952	91.70	gold quality
ganglionic eminence	UBERON:0004023	91.62	gold quality
right adrenal gland	UBERON:0001233	91.57	gold quality
left adrenal gland	UBERON:0001234	91.50	gold quality
left uterine tube	UBERON:0001303	91.46	gold quality
left adrenal gland cortex	UBERON:0035825	91.43	gold quality
lung	UBERON:0002048	91.39	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.33	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-MTAB-7381	yes	249.70
E-MTAB-6701	yes	114.69
E-HCAD-1	yes	57.18
E-MTAB-10287	yes	33.19
E-CURD-122	yes	31.65
E-GEOD-134144	yes	29.15
E-HCAD-10	yes	26.71
E-CURD-46	yes	22.98
E-GEOD-125970	yes	22.40
E-MTAB-8410	yes	20.58
E-CURD-88	yes	16.49
E-ANND-3	yes	10.20
E-MTAB-10042	yes	4.37
E-MTAB-7606	no	552.38
E-GEOD-99795	no	64.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting CKLF, 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-4682	100.00	68.89	1258
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-4424	98.91	70.33	1145
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-4771	97.43	67.69	596
HSA-MIR-509-3-5P	97.21	67.74	1517
HSA-MIR-509-5P	97.21	67.90	1512
HSA-MIR-4418	97.04	67.16	1372
HSA-MIR-4491	96.53	66.20	935
HSA-MIR-4657	96.53	66.57	895

Literature-anchored findings (GeneRIF, showing 17)

• CKLF1 could increase the proliferation of human bone marrow hematopoietic progenitor cells and colony formation (PMID:12411060)
• Results confirm that the secreted peptides of CKLF1, C27 and C19, have functional activation via CCR4. (PMID:18069042)
• Chemokine-like factor expression is differentially regulated in myoblasts and myotubes and thrombin could be a strong regulator for its expression (PMID:18294340)
• The expression of CKLF1 is up-regulated in atherosclerotic plaques. (PMID:20137403)
• CKLF1-C19 and -C27 can stimulate antigen-presenting capability of dendritic cells (PMID:20392439)
• CKLF1 can induce proliferation and inhibit apoptosis of human vascular smooth muscle cell through the down-regulation of Bax and Caspase-3 and the up-regulation of Bcl-2 expression. (PMID:23253812)
• Chemokine-like factor 1 is over-expressed in patients with atopic dermatitis. (PMID:23983609)
• role in the pathogenesis of psoriasis by promoting the proliferation of microvascular endothelial cells (PMID:25915746)
• CKLF1 expression was up-regulated in synovim from rheumatoid arthritis and ankylosing spondylitis patients. (PMID:26838743)
• expression elevated in the skin of keloid patients (PMID:26986142)
• Data indicate that leukocyte-infiltrate derived chemokine-like factor (CKLF) expression is a candidate biomarker of favorable prognosis. (PMID:27153559)
• Chemokine-like factor 1 (CKLF1) aggravates neointimal hyperplasia through activating the NF-kappaB /VCAM-1 pathway. (PMID:32741140)
• Kanglaite enhances the efficacy of cisplatin in suppression of hepatocellular carcinoma via inhibiting CKLF1 mediated NF-kappaB pathway and regulating transporter mediated drug efflux. (PMID:32918990)
• CKLF and IL1B transcript levels at diagnosis are predictive of relapse in children with pre-B-cell acute lymphoblastic leukaemia. (PMID:33620089)
• Neuronal chemokine-like-factor 1 (CKLF1) up-regulation promotes M1 polarization of microglia in rat brain after stroke. (PMID:34385606)
• Research insights into the chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTM): their roles in various tumors. (PMID:38223763)
• CKLF instigates a “cold” microenvironment to promote MYCN-mediated tumor aggressiveness. (PMID:38489372)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cklf	ENSMUSG00000054400
rattus_norvegicus	Cklf	ENSRNOG00000012752
caenorhabditis_elegans	F28H1.4	WBGENE00017909
caenorhabditis_elegans	F47B3.3	WBGENE00018527

Paralogs (14): CMTM1 (ENSG00000089505), CMTM6 (ENSG00000091317), PLP2 (ENSG00000102007), PLLP (ENSG00000102934), CMTM3 (ENSG00000140931), CMTM2 (ENSG00000140932), MALL (ENSG00000144063), MAL2 (ENSG00000147676), CMTM7 (ENSG00000153551), MARVELD1 (ENSG00000155254), CMTM5 (ENSG00000166091), CMTM8 (ENSG00000170293), MAL (ENSG00000172005), CMTM4 (ENSG00000183723)

Protein

Protein identifiers

Chemokine-like factor — Q9UBR5 (reviewed: Q9UBR5)

Alternative names: C32

All UniProt accessions (3): Q9UBR5, E9PLU7, Q5BJH6

UniProt curated annotations — full annotation on UniProt →

Function. May play an important role in inflammation and regeneration of skeletal muscle. Essential for embryonic development. Has chemotactic response in monocytes, neutrophils and lymphocytes. Binds CCR4.

Subcellular location. Secreted Membrane Membrane.

Tissue specificity. Isoform 1, isoform 2, isoform 3 and isoform 4 have highest expression levels in adult spleen, lung, testis, ovary, peripheral blood leukocyte, placenta, pancreas, and in fetal brain, skeletal muscle, thymus and heart. Lower expression levels in adult skeletal muscle, liver, thymus colon, prostate and fetal spleen and liver.

Activity regulation. Partly inhibited by interleukin 10.

Similarity. Belongs to the chemokine-like factor family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9UBR5-1	2, CKLF2	yes
Q9UBR5-2	1, CKLF1
Q9UBR5-3	3, CKLF3
Q9UBR5-4	4, CKLF4
Q9UBR5-5	5

RefSeq proteins (5): NP_001035228, NP_057410, NP_058647, NP_857591, NP_857592 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008253	Marvel	Domain
IPR050578	MARVEL-CKLF_proteins	Family

UniProt features (9 total): splice variant 4, transmembrane region 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBR5-F1	76.68	0.30

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 209 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, TGCGCANK_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_LEUKOCYTE_CHEMOTAXIS, PATIL_LIVER_CANCER, GOBP_TAXIS, GOBP_LEUKOCYTE_MIGRATION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, GOBP_GRANULOCYTE_MIGRATION

GO Biological Process (7): neutrophil chemotaxis (GO:0030593), secretion by cell (GO:0032940), macrophage chemotaxis (GO:0048246), lymphocyte chemotaxis (GO:0048247), chemotaxis (GO:0006935), signal transduction (GO:0007165), leukocyte chemotaxis (GO:0030595)

GO Molecular Function (3): chemokine activity (GO:0008009), cytokine activity (GO:0005125), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
leukocyte chemotaxis	2
cell chemotaxis	2
cellular anatomical structure	2
granulocyte chemotaxis	1
neutrophil migration	1
secretion	1
export from cell	1
macrophage migration	1
lymphocyte migration	1
response to chemical	1
taxis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
leukocyte migration	1
cytokine activity	1
chemokine receptor binding	1
receptor ligand activity	1
binding	1

Protein interactions and networks

STRING

280 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CKLF	CMTM2	Q8TAZ6	968
CKLF	CMTM3	Q96MX0	967
CKLF	CMTM7	Q96FZ5	964
CKLF	CMTM4	Q8IZR5	963
CKLF	CMTM6	Q9NX76	959
CKLF	CMTM5	Q96DZ9	945
CKLF	CMTM8	Q8IZV2	939
CKLF	PLLP	Q9Y342	845
CKLF	CCL17	Q92583	578
CKLF	CCL22	O00626	538
CKLF	CX3CL1	P78423	475
CKLF	MYADM	Q96S97	457
CKLF	TSPAN1	O60635	447
CKLF	AGER	Q15109	418
CKLF	CMTM1	Q8IZ96	407

IntAct

7 interactions, top by confidence:

A	B	Type	Score
LRP6	CKLF	psi-mi:“MI:0915”(physical association)	0.560
CKLF	HOXB9	psi-mi:“MI:0915”(physical association)	0.400
CKLF	GLIPR1	psi-mi:“MI:0915”(physical association)	0.400
ECE1	CKLF	psi-mi:“MI:0915”(physical association)	0.370
LRP6	CKLF	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): HOXB9 (Affinity Capture-MS), APOB (Affinity Capture-MS), CKLF (Affinity Capture-RNA), CKLF (Two-hybrid), HOXB9 (Affinity Capture-MS), GLIPR1 (Affinity Capture-MS), CKLF (Affinity Capture-RNA)

ESM2 similar proteins: A0A2R8RY99, A0PK11, A1XGB4, A2VDC7, A3KQ86, A7E3W5, A8MWL6, A9CAZ8, B2RVW2, B9SXY8, E9QHT9, H9JBU5, O43759, O43760, O54980, O55100, O55101, P36963, P36965, P49111, P56557, P58418, Q0P442, Q0P467, Q13491, Q3SZL9, Q3T110, Q566G2, Q5R4C3, Q5R603, Q5R703, Q62876, Q63ZU3, Q64302, Q6AYR5, Q6DFR5, Q7T392, Q7Z0Q2, Q8BGA2, Q8BHH8

Diamond homologs: Q8IZ96, Q9DAS1, Q9JK79, Q9UBR5, Q8TAZ6, Q9DAC0, Q9DAR1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

649 predictions. Top by Δscore:

Variant	Effect	Δscore
16:66563215:GGG:G	donor_gain	1.0000
16:66563216:GG:G	donor_gain	1.0000
16:66563216:GGG:G	donor_gain	1.0000
16:66563217:GG:G	donor_gain	1.0000
16:66566000:G:GT	donor_gain	1.0000
16:66563213:GAGGG:G	donor_gain	0.9900
16:66563218:G:C	donor_loss	0.9900
16:66563218:G:GG	donor_gain	0.9900
16:66563219:TAA:T	donor_loss	0.9900
16:66563220:A:T	donor_loss	0.9900
16:66563221:A:AA	donor_loss	0.9900
16:66563222:G:C	donor_loss	0.9900
16:66566003:GTTTT:G	donor_gain	0.9900
16:66566004:T:G	donor_gain	0.9900
16:66552687:A:T	donor_gain	0.9800
16:66552789:GGCTG:G	donor_gain	0.9800
16:66552790:GCTG:G	donor_gain	0.9800
16:66552790:GCTGG:G	donor_gain	0.9800
16:66552794:G:GG	donor_gain	0.9800
16:66558345:GCTT:G	donor_gain	0.9800
16:66558349:G:GG	donor_gain	0.9800
16:66563219:T:TA	donor_loss	0.9800
16:66563221:A:AC	donor_loss	0.9800
16:66563222:G:A	donor_loss	0.9800
16:66565880:TTCCA:T	acceptor_loss	0.9800
16:66565881:TCCA:T	acceptor_loss	0.9800
16:66565882:CCAG:C	acceptor_loss	0.9800
16:66565885:GGT:G	acceptor_gain	0.9800
16:66565942:G:GT	donor_gain	0.9800
16:66552791:CTGG:C	donor_loss	0.9700

AlphaMissense

981 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:66558337:T:A	W76R	0.995
16:66558337:T:C	W76R	0.995
16:66563133:C:A	N83K	0.993
16:66563133:C:G	N83K	0.993
16:66552781:G:C	K22N	0.990
16:66552781:G:T	K22N	0.990
16:66558259:G:A	G50R	0.989
16:66558259:G:C	G50R	0.989
16:66563123:A:C	D80A	0.988
16:66563213:G:A	G110E	0.987
16:66563122:G:C	D80H	0.986
16:66552752:T:C	F13L	0.985
16:66552754:C:A	F13L	0.985
16:66552754:C:G	F13L	0.985
16:66558339:G:C	W76C	0.985
16:66558339:G:T	W76C	0.985
16:66563216:G:A	G111E	0.985
16:66563215:G:A	G111R	0.984
16:66563215:G:C	G111R	0.984
16:66565910:T:C	C120R	0.984
16:66558266:A:T	E52V	0.983
16:66552770:G:C	G19R	0.982
16:66563124:T:A	D80E	0.982
16:66563124:T:G	D80E	0.982
16:66563123:A:G	D80G	0.981
16:66563212:G:A	G110R	0.981
16:66563212:G:C	G110R	0.981
16:66552779:A:G	K22E	0.980
16:66558260:G:A	G50E	0.980
16:66563122:G:A	D80N	0.980

dbSNP variants (sampled 300 via entrez): RS1000375684 (16:66560839 T>A,C), RS1000388020 (16:66552895 C>G,T), RS1000665043 (16:66562398 A>G), RS1000685295 (16:66560529 G>A), RS1000778372 (16:66554411 T>G), RS1000962458 (16:66563673 T>C), RS1001247706 (16:66562893 GT>G,GTT), RS1001506124 (16:66561472 G>A), RS1001545399 (16:66561106 A>G), RS1001839944 (16:66563042 G>C,T), RS1001872541 (16:66562814 G>A,C), RS1001940212 (16:66554907 G>A), RS1003517559 (16:66564749 C>T), RS1003545130 (16:66559115 C>T), RS1003548706 (16:66564571 C>G,T)

Disease associations

OMIM: gene MIM:616074 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
bisphenol A	affects expression, affects cotreatment, increases expression	2
cobaltous chloride	decreases expression	2
Estradiol	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
AM 251	increases expression	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
abrine	decreases expression	1
kang-lai-te	decreases reaction, increases phosphorylation, increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	decreases expression, affects cotreatment	1
Cisplatin	increases expression, decreases reaction, increases phosphorylation	1
Coumestrol	affects cotreatment, increases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Dimethyl Sulfoxide	affects expression	1
Folic Acid	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Indomethacin	affects cotreatment, increases expression	1
Mitoxantrone	affects response to substance	1

Clinical trials (associated diseases)

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