CYTL1

Summary

CYTL1 (cytokine like 1, HGNC:24435) is a protein-coding gene on chromosome 4p16.2, encoding Cytokine-like protein 1 (Q9NRR1).

C17 is a cytokine-like protein specifically expressed in bone marrow and cord blood mononuclear cells that bear the CD34 (MIM 142230) surface marker (Liu et al., 2000 [PubMed 10857752]).

Source: NCBI Gene 54360 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_018659

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24435
Approved symbol	CYTL1
Name	cytokine like 1
Location	4p16.2
Locus type	gene with protein product
Status	Approved
Aliases	C17, C4orf4
Ensembl gene	ENSG00000170891
Ensembl biotype	protein_coding
OMIM	607930
Entrez	54360

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000307746, ENST00000506508, ENST00000509419, ENST00000917270

RefSeq mRNA: 1 — MANE Select: NM_018659 NM_018659

CCDS: CCDS3379

Canonical transcript exons

ENST00000307746 — 4 exons

Exon	Start	End
ENSE00001134932	5014586	5015234
ENSE00001640572	5017135	5017179
ENSE00001740726	5019293	5019458
ENSE00001746109	5016836	5016964

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 99.52.

FANTOM5 (CAGE): breadth broad, TPM avg 8.2687 / max 730.5290, expressed in 682 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51210	8.1063	676
51211	0.1624	81

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.52	gold quality
trachea	UBERON:0003126	98.89	gold quality
ascending aorta	UBERON:0001496	96.29	gold quality
thoracic aorta	UBERON:0001515	96.16	gold quality
descending thoracic aorta	UBERON:0002345	95.02	gold quality
cartilage tissue	UBERON:0002418	90.00	gold quality
aorta	UBERON:0000947	88.08	gold quality
trabecular bone tissue	UBERON:0002483	82.91	gold quality
endocervix	UBERON:0000458	82.20	gold quality
popliteal artery	UBERON:0002250	82.14	gold quality
tibial artery	UBERON:0007610	82.12	gold quality
ectocervix	UBERON:0012249	81.86	gold quality
body of uterus	UBERON:0009853	80.26	gold quality
left uterine tube	UBERON:0001303	78.17	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.71	gold quality
right coronary artery	UBERON:0001625	77.19	gold quality
left coronary artery	UBERON:0001626	76.99	gold quality
right uterine tube	UBERON:0001302	76.55	gold quality
placenta	UBERON:0001987	76.27	gold quality
coronary artery	UBERON:0001621	75.44	gold quality
spinal cord	UBERON:0002240	74.41	gold quality
gall bladder	UBERON:0002110	73.98	gold quality
prostate gland	UBERON:0002367	73.33	gold quality
muscle layer of sigmoid colon	UBERON:0035805	72.93	gold quality
seminal vesicle	UBERON:0000998	72.76	gold quality
lymph node	UBERON:0000029	72.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	72.44	gold quality
lower esophagus	UBERON:0013473	72.30	gold quality
vagina	UBERON:0000996	72.20	gold quality
urinary bladder	UBERON:0001255	71.92	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-10137	yes	758.88
E-MTAB-9067	yes	551.10
E-MTAB-10432	yes	384.50
E-MTAB-7407	yes	276.24
E-HCAD-4	yes	235.48
E-MTAB-8207	yes	94.78
E-HCAD-6	yes	51.35
E-HCAD-1	yes	13.52
E-MTAB-6701	yes	13.42
E-CURD-112	yes	10.14
E-MTAB-8884	no	651.77
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting CYTL1, 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-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-100-3P	99.20	67.33	672
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-937-5P	97.43	68.39	667

Literature-anchored findings (GeneRIF, showing 17)

• We report a structural-functional characterization of cytokine-like protein 1 (Cytl1) by a combination of different computational structure-based techniques. (PMID:21322034)
• C17orf62-L could induce cell death accompanied with rising of cleaved PARP. (PMID:21503106)
• C17 as a cytokine that s contributes to immune homeostasis systemically or in a tissue-specific manner in the joint (PMID:21799806)
• The DNA methylation pattern of the CYTL1 promoter region was significantly different between early and advanced stages of squamous cell carcinoma. (PMID:22011669)
• evidence suggests that ANKRD7 and CYTL1 genes may play an important role in the variance in alcohol drinking risk (PMID:22613542)
• our results showed the first evidence of CYTL1 expression in SH-SY5Y neuroblastoma cells and human NB tissues, revealed a possible link between CYTL1 and NB development (PMID:22797702)
• Cytl1 is highly expressed in the endometrium during the embryo implantation and its expression is regulated by ovarian hormones. Cytl1 enhances endometrial proliferation, induces the secretion of endometrial LIF and HB-EGF, and even enhances endometrial cell adhesion to trophoblastic cells. These indicate that Cytl1 is a potential molecular mediator of embryo is a potential molecular mediator in embryo implantation. (PMID:26800213)
• role in regulation embryo implantation (PMID:26800213)
• when the native signal peptide of CYTL1 was replaced by IgGkappaSP, the expression and secretion was increased by 4 fold. (PMID:26922322)
• this study shows that CYTL1 possesses chemotactic activity and demonstrates that its functional receptor is CCR2B (PMID:27084102)
• Circular dichroism analysis showed that, like chemokines, CYTL1has a higher content of beta-sheet than alpha-helix secondary structure; recombinant CYTL1 promoted calcium flux in chondrocytes; unlike chemokines, CYTL1 had limited affinity to proteoglycans; together, these properties further support cytokine-like properties for CYTL1 with some overlap with the chemokines (PMID:28478073)
• CYTL1 can mediate proangiogenic functions ascribed to endothelial progenitors and may be a candidate to support vessel formation and tissue regeneration in ischemic pathologies. (PMID:30582450)
• Results collectively suggest that CYTL1 negatively regulates the osteogenesis of MSCs and positively regulates osteoclastogenesis to modulate bone mass. (PMID:30718470)
• The involvement of cytokine-like 1 (Cytl1) in chondrogenesis and cartilage metabolism. (PMID:32736681)
• Cytokine-like protein 1-induced survival of monocytes suggests a combined strategy targeting MCL1 and MAPK in CMML. (PMID:33690800)
• Intracellular CYTL1, a novel tumor suppressor, stabilizes NDUFV1 to inhibit metabolic reprogramming in breast cancer. (PMID:35115484)
• Cytokine-Like Protein 1 (CYTL1) as a Key Target of M-Stage Immune Infiltration in Stomach Adenocarcinoma. (PMID:36825034)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cytl1	ENSDARG00000110744
mus_musculus	Cytl1	ENSMUSG00000062329
rattus_norvegicus	Cytl1	ENSRNOG00000028108

Protein

Protein identifiers

Cytokine-like protein 1 — Q9NRR1 (reviewed: Q9NRR1)

Alternative names: Protein C17

All UniProt accessions (3): Q9NRR1, H0Y8Q4, H0Y9X7

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Specifically expressed in CD34+ hematopoietic cells.

RefSeq proteins (1): NP_061129* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029253	CYTL1	Family

Pfam: PF15153

UniProt features (4 total): sequence variant 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRR1-F1	85.86	0.59

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 110 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, HORIUCHI_WTAP_TARGETS_DN, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CHONDROITIN_SULFATE_PROTEOGLYCAN_BIOSYNTHETIC_PROCESS, GOBP_EAR_DEVELOPMENT, ROZANOV_MMP14_TARGETS_UP, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_CHONDROCYTE_DIFFERENTIATION, chr4p16, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, SABATES_COLORECTAL_ADENOMA_DN, GOBP_CONNECTIVE_TISSUE_DEVELOPMENT

GO Biological Process (7): chondrocyte differentiation (GO:0002062), transcription by RNA polymerase II (GO:0006366), signal transduction (GO:0007165), positive regulation of transcription by RNA polymerase II (GO:0045944), inner ear development (GO:0048839), chondroitin sulfate proteoglycan biosynthetic process (GO:0050650), cartilage homeostasis (GO:1990079)

GO Molecular Function (1): signaling receptor binding (GO:0005102)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	1
cartilage development	1
DNA-templated transcription	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
ear development	1
anatomical structure development	1
proteoglycan biosynthetic process	1
chondroitin sulfate proteoglycan metabolic process	1
protein O-linked glycosylation via xylose	1
tissue homeostasis	1
protein binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

632 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYTL1	CD34	P28906	521
CYTL1	FAM167B	Q9BTA0	518
CYTL1	CLEC3A	O75596	481
CYTL1	ACSM4	P0C7M7	436
CYTL1	TEX26	Q8N6G2	416
CYTL1	C22orf39	Q6P5X5	382
CYTL1	CCM2	Q9BSQ5	380
CYTL1	UCMA	Q8WVF2	374
CYTL1	CILP2	Q8IUL8	370
CYTL1	CILP	O75339	358
CYTL1	TNFRSF11B	O00300	354
CYTL1	CFAP100	Q494V2	350
CYTL1	A0A0J9YVX5	A0A0J9YVX5	344
CYTL1	RHNO1	Q9BSD3	344
CYTL1	GOPC	Q9HD26	344

IntAct

0 interactions, top by confidence:

BioGRID (1): CYTL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUA7, A0A3Q1LRJ2, A2T6Z6, E9Q8Q8, O46673, O77049, O88823, P01588, P07865, P22301, P29676, P43480, P46651, P48411, P51496, P51497, P51746, P55029, P79338, Q0Z972, Q25BC1, Q28374, Q28C41, Q2PE73, Q3KNT9, Q4VK74, Q5Q0V6, Q5ZJY9, Q6A2H4, Q6AY06, Q6H8S9, Q6H8T0, Q6H8T1, Q6H8T2, Q6UXV1, Q865X4, Q8BGT0, Q8CGK6, Q8CJ70, Q8IU54

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

411 predictions. Top by Δscore:

Variant	Effect	Δscore
4:5019287:ACTCA:A	donor_loss	1.0000
4:5019288:CT:C	donor_loss	1.0000
4:5019291:A:AC	donor_gain	1.0000
4:5019292:C:CA	donor_loss	1.0000
4:5019292:C:CC	donor_gain	1.0000
4:5015230:AAATC:A	acceptor_gain	0.9900
4:5015231:AATCC:A	acceptor_loss	0.9900
4:5015233:TC:T	acceptor_gain	0.9900
4:5015233:TCCTG:T	acceptor_loss	0.9900
4:5015234:CC:C	acceptor_gain	0.9900
4:5015234:CCT:C	acceptor_loss	0.9900
4:5015235:C:CC	acceptor_gain	0.9900
4:5015236:T:C	acceptor_loss	0.9900
4:5016834:A:AC	donor_gain	0.9900
4:5016834:ACTCT:A	donor_gain	0.9900
4:5016835:C:CC	donor_gain	0.9900
4:5016835:CT:C	donor_gain	0.9900
4:5016835:CTCT:C	donor_gain	0.9900
4:5016835:CTCTC:C	donor_gain	0.9900
4:5017133:A:AC	donor_gain	0.9900
4:5017134:C:CC	donor_gain	0.9900
4:5019292:CCG:C	donor_gain	0.9900
4:5015231:AATC:A	acceptor_gain	0.9800
4:5015232:ATC:A	acceptor_gain	0.9800
4:5015246:G:C	acceptor_gain	0.9800
4:5016838:T:A	donor_gain	0.9800
4:5019292:CCGA:C	donor_gain	0.9800
4:5019301:CCGAG:C	donor_gain	0.9800
4:5015244:A:AC	acceptor_gain	0.9700
4:5016962:ATTC:A	acceptor_loss	0.9700

AlphaMissense

859 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:5015224:A:C	F113C	0.995
4:5016843:C:T	C107Y	0.995
4:5015223:G:C	F113L	0.994
4:5015223:G:T	F113L	0.994
4:5015225:A:G	F113L	0.994
4:5016843:C:G	C107S	0.994
4:5016844:A:T	C107S	0.994
4:5016957:C:G	C69S	0.992
4:5016958:A:T	C69S	0.992
4:5016842:G:C	C107W	0.991
4:5016843:C:A	C107F	0.990
4:5016933:A:C	F77C	0.990
4:5016957:C:T	C69Y	0.990
4:5016962:A:C	N67K	0.990
4:5016962:A:T	N67K	0.990
4:5016844:A:G	C107R	0.989
4:5015209:C:G	C118S	0.986
4:5015210:A:T	C118S	0.986
4:5016942:A:G	L74P	0.985
4:5016915:C:G	C83S	0.984
4:5016916:A:T	C83S	0.984
4:5016956:A:C	C69W	0.983
4:5016957:C:A	C69F	0.983
4:5019366:C:T	C27Y	0.983
4:5016963:T:A	N67I	0.982
4:5015209:C:T	C118Y	0.981
4:5015224:A:G	F113S	0.981
4:5016914:A:C	C83W	0.981
4:5016915:C:T	C83Y	0.981
4:5016933:A:G	F77S	0.980

dbSNP variants (sampled 300 via entrez): RS10002918 (4:5017880 G>A,T), RS10006676 (4:5019359 G>T), RS1000954058 (4:5017211 C>G), RS1001954729 (4:5015329 C>T), RS1002403088 (4:5020572 A>T), RS1002772405 (4:5019601 C>G,T), RS10031270 (4:5015781 T>A,G), RS1003411922 (4:5019022 T>TTG), RS1003517454 (4:5019907 G>C,T), RS1003764106 (4:5019347 G>A,C), RS1004030796 (4:5014192 A>G), RS1004659484 (4:5014295 T>C,G), RS1004834029 (4:5017224 C>A,G), RS1005266462 (4:5019591 C>A,T), RS1006474975 (4:5015764 A>T)

Disease associations

OMIM: gene MIM:607930 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST002647_20	Height	4.000000e-11
GCST003097_37	Pediatric autoimmune diseases	1.000000e-07
GCST006585_2622	Blood protein levels	1.000000e-32
GCST009391_1264	Metabolite levels	9.000000e-06
GCST010244_307	Triglyceride levels	6.000000e-12
GCST90020024_1239	A body shape index	4.000000e-15
GCST90020024_1240	A body shape index	3.000000e-10
GCST90020024_670	A body shape index	1.000000e-08
GCST90020025_1048	Waist-to-hip ratio adjusted for BMI	9.000000e-27
GCST90020025_1049	Waist-to-hip ratio adjusted for BMI	7.000000e-09
GCST90020025_1050	Waist-to-hip ratio adjusted for BMI	2.000000e-09
GCST90020025_301	Waist-to-hip ratio adjusted for BMI	4.000000e-10
GCST90020026_278	Hip index	4.000000e-12
GCST90020027_1872	Waist-hip index	2.000000e-27
GCST90020027_1873	Waist-hip index	1.000000e-08
GCST90020027_1874	Waist-hip index	8.000000e-11
GCST90020027_1875	Waist-hip index	5.000000e-11
GCST90020028_1708	Hip circumference adjusted for BMI	2.000000e-08
GCST90020029_683	Waist circumference adjusted for body mass index	1.000000e-14
GCST90020029_684	Waist circumference adjusted for body mass index	9.000000e-15
GCST90020029_685	Waist circumference adjusted for body mass index	1.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004761	uric acid measurement
EFO:0004530	triglyceride measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	7
trichostatin A	affects cotreatment, increases expression	3
Arsenic Trioxide	affects binding, decreases reaction, decreases expression, affects cotreatment	3
Tretinoin	affects cotreatment, decreases expression	3
Vorinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation	2
Nickel	decreases expression	2
GSK-J4	decreases expression	1
bisphenol A	increases expression	1
deoxynivalenol	decreases expression	1
terbufos	increases methylation	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
beta-methylcholine	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
Carbamazepine	affects expression	1
Fonofos	increases methylation	1
Estradiol	increases expression	1
Hydrogen Peroxide	decreases expression	1
Parathion	increases methylation	1
T-2 Toxin	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Triclosan	increases expression	1
Reactive Oxygen Species	affects expression	1
Palmitic Acid	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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