IL17B

Summary

IL17B (interleukin 17B, HGNC:5982) is a protein-coding gene on chromosome 5q32, encoding Interleukin-17B (Q9UHF5). Stimulates the release of tumor necrosis factor alpha and IL-1-beta from the monocytic cell line THP-1.

The protein encoded by this gene is a T cell-derived cytokine that shares sequence similarity with IL17. This cytokine was reported to stimulate the release of TNF alpha (TNF) and IL1 beta (IL1B) from a monocytic cell line. Immunohistochemical analysis of several nerve tissues indicated that this cytokine is primarily localized to neuronal cell bodies. Alternative splicing results in multiple splice variants.

Source: NCBI Gene 27190 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_014443

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5982
Approved symbol	IL17B
Name	interleukin 17B
Location	5q32
Locus type	gene with protein product
Status	Approved
Aliases	IL-17B, ZCYTO7, IL-20, MGC138900, MGC138901, NIRF
Ensembl gene	ENSG00000127743
Ensembl biotype	protein_coding
OMIM	604627
Entrez	27190

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000261796, ENST00000505432, ENST00000518814

RefSeq mRNA: 2 — MANE Select: NM_014443 NM_001317987, NM_014443

CCDS: CCDS4297

Canonical transcript exons

ENST00000261796 — 3 exons

Exon	Start	End
ENSE00001033062	149379205	149379292
ENSE00001237745	149374267	149374600
ENSE00003572547	149376736	149377025

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 95.38.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4254 / max 387.9363, expressed in 78 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64121	0.4254	78

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	95.38	gold quality
oocyte	CL:0000023	93.00	gold quality
tibial nerve	UBERON:0001323	89.42	gold quality
secondary oocyte	CL:0000655	86.90	gold quality
olfactory bulb	UBERON:0002264	86.53	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.88	gold quality
popliteal artery	UBERON:0002250	84.48	gold quality
tibial artery	UBERON:0007610	84.43	gold quality
aorta	UBERON:0000947	82.66	gold quality
descending thoracic aorta	UBERON:0002345	81.38	gold quality
thoracic aorta	UBERON:0001515	80.49	gold quality
ascending aorta	UBERON:0001496	80.44	gold quality
trigeminal ganglion	UBERON:0001675	75.39	gold quality
blood vessel layer	UBERON:0004797	74.90	silver quality
lower esophagus muscularis layer	UBERON:0035833	74.45	gold quality
lower esophagus	UBERON:0013473	74.40	gold quality
cartilage tissue	UBERON:0002418	73.79	silver quality
right coronary artery	UBERON:0001625	73.73	gold quality
left coronary artery	UBERON:0001626	73.56	gold quality
saphenous vein	UBERON:0007318	73.19	silver quality
dorsal root ganglion	UBERON:0000044	73.04	silver quality
coronary artery	UBERON:0001621	72.79	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	72.55	gold quality
sural nerve	UBERON:0015488	70.93	gold quality
muscle layer of sigmoid colon	UBERON:0035805	70.92	gold quality
body of uterus	UBERON:0009853	70.75	gold quality
right adrenal gland cortex	UBERON:0035827	69.88	gold quality
right adrenal gland	UBERON:0001233	69.65	gold quality
left adrenal gland	UBERON:0001234	68.58	gold quality
mucosa of stomach	UBERON:0001199	68.23	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting IL17B, 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-4697-3P	99.89	67.09	1123
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-18A-5P	99.29	71.05	806
HSA-MIR-18B-5P	99.29	71.05	806
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-4735-3P	99.14	69.85	777
HSA-MIR-1245B-5P	98.88	66.55	576
HSA-MIR-3142	98.88	66.09	529

Literature-anchored findings (GeneRIF, showing 15)

• IL-17 may play an important role in the occurrence of nasal polyps by overexpression. (PMID:16805377)
• expression and functional study of IL-17B (PMID:22394632)
• IL-17A, IL-17B, IL-17F and IL-23 in systemic lupus erythematosus patients were examined and the correlation between levels of the investigated cytokines and VEGF, PIGF, as well as number of endothelial cells, was investigated. (PMID:23661335)
• Results show that amplified signaling of interleukin-17 receptor B (IL-17RB) and its ligand IL-17B promot tumorigenicity in breast cancer cells and impeded acinus formation in immortalized normal mammary epithelial cells. (PMID:23851503)
• IL-17B can enhance the effects of TNF-alpha on the production of cytokines and chemokines that control immune cell trafficking and neutrophil homeostasis in the inflamed tissues. (PMID:24056520)
• IL-17B-IL-17RB signaling promotes pancreatic cancer malignancy. (PMID:25732306)
• Studies indicate that interleukin 17 (IL-17B)/interleukin 17 receptor B (IL-17RB) signaling is essential for pancreatic cancer malignancy. (PMID:26285835)
• The results indicate that the IL-17B/IL-17RB signaling can promote the growth and migration of tumor cells. (PMID:27146881)
• Segregation analysis revealed that variants c.475T>G in SKP1, c.671G>A in PROB1, and c.527G>A in IL17B in the 5q31.1-q35.3 linkage region, and c.850G>A in HKDC1 in the 10q22 locus completely segregated with the phenotype in the studied Keratoconus family (PMID:27703147)
• Our data revealed a new mechanism that IL-17B enhanced the progression of gastric cancer by activating mesenchymal stem cells. (PMID:28145881)
• This comprehensive review details the recognition of activity, signaling, and the roles of IL17B-IL17RB in breast cancer have caused to determination of new therapeutic mechanisms–{REVIEW} (PMID:28160754)
• Gene expression microarray analysis followed by Kaplan-Meier survival curve showed that high expression level of IL-17B was associated with poor survival of patients with lung neoplasm. (PMID:29496538)
• Our data reveal that analogous to other IL-17 family members, IL-17B has an inflammatory role in the human system. (PMID:30770417)
• Potential role of INTERLEUKIN-17 in the pathogenesis of oral lichen planus: a systematic review with META-analysis. (PMID:35570406)
• Variants of IL6, IL10, FCN2, RNASE3, IL12B and IL17B loci are associated with Schistosoma mansoni worm burden in the Albert Nile region of Uganda. (PMID:38033168)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Il17b	ENSMUSG00000024578
rattus_norvegicus	Il17b	ENSRNOG00000019695

Paralogs (5): IL17A (ENSG00000112115), IL17F (ENSG00000112116), IL17C (ENSG00000124391), IL25 (ENSG00000166090), IL17D (ENSG00000172458)

Protein

Protein identifiers

Interleukin-17B — Q9UHF5 (reviewed: Q9UHF5)

Alternative names: Cytokine Zcyto7, Interleukin-20, Neuronal interleukin-17-related factor

All UniProt accessions (1): Q9UHF5

UniProt curated annotations — full annotation on UniProt →

Function. Stimulates the release of tumor necrosis factor alpha and IL-1-beta from the monocytic cell line THP-1.

Subcellular location. Secreted.

Tissue specificity. Expressed in adult pancreas, small intestine, stomach, spinal cord and testis. Less pronounced expression in prostate, colon mucosal lining, and ovary.

Similarity. Belongs to the IL-17 family.

RefSeq proteins (1): NP_055258* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010345	IL-17_fam	Family
IPR020440	IL-17_chr	Family
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF06083

UniProt features (6 total): disulfide bond 2, signal peptide 1, chain 1, region of interest 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHF5-F1	78.34	0.48

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): 121–176, 126–178

Glycosylation sites (1): 75

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 113 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, PAX4_01, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GCANCTGNY_MYOD_Q6, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, GOBP_CELL_CELL_SIGNALING, SRF_Q5_01, SRF_01, SRF_C, GATA3_01, AML_Q6

GO Biological Process (5): inflammatory response (GO:0006954), immune response (GO:0006955), cell-cell signaling (GO:0007267), positive regulation of cytokine production involved in inflammatory response (GO:1900017), signal transduction (GO:0007165)

GO Molecular Function (1): cytokine activity (GO:0005125)

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 communication	2
signaling	2
defense response	1
immune system process	1
response to stimulus	1
positive regulation of cytokine production	1
cytokine production involved in inflammatory response	1
regulation of cytokine production involved in inflammatory response	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
receptor ligand activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

586 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL17B	IL17RB	Q9NRM6	999
IL17B	IL25	Q9H293	991
IL17B	IL17RA	Q96F46	963
IL17B	IL17RE	Q8NFR9	933
IL17B	IL17RD	Q8NFM7	852
IL17B	IL17RC	Q8NAC3	843
IL17B	IL17D	Q8TAD2	641
IL17B	CXCL8	P10145	617
IL17B	CD4	P01730	610
IL17B	IL17C	Q9P0M4	609
IL17B	IL13	P35225	595
IL17B	IL17F	Q96PD4	590
IL17B	IL17A	Q16552	589
IL17B	IL5	P05113	572
IL17B	CCL11	P50877	572

IntAct

5 interactions, top by confidence:

A	B	Type	Score
IL17B	HNRNPA2B1	psi-mi:“MI:0915”(physical association)	0.400
IL17B	DCTN6	psi-mi:“MI:0914”(association)	0.350
IL17B	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
ENO2	IL17B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (78): IL17B (Two-hybrid), IL17B (Proximity Label-MS), IL17B (Reconstituted Complex), ERBB2IP (Affinity Capture-MS), KBTBD7 (Affinity Capture-MS), KBTBD6 (Affinity Capture-MS), HIST1H1C (Affinity Capture-MS), STAU1 (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS), RPL32 (Affinity Capture-MS), RBM28 (Affinity Capture-MS), DPH1 (Affinity Capture-MS), DPH2 (Affinity Capture-MS), DCTN6 (Affinity Capture-MS), LLPH (Affinity Capture-MS)

ESM2 similar proteins: A6N6I9, B0VXV3, B0VXV4, C0K3N1, O40633, O46526, P00683, P0DW98, P24916, P34129, P49764, P50412, P67861, P67862, P67863, Q16552, Q330K6, Q3HRV3, Q3S2X5, Q5BJ95, Q60I29, Q61453, Q62386, Q63434, Q687Y7, Q6J936, Q7TNI7, Q8K4C5, Q8SPN3, Q8SPN4, Q8VD87, Q8VHH8, Q90X23, Q90X24, Q96PD4, Q9D244, Q9P0M4, Q9QXT6, Q9QYX2, Q9QYX3

Diamond homologs: A6N6I9, O40633, P24916, Q16552, Q5BJ95, Q60I29, Q61453, Q62386, Q687Y7, Q7TNI7, Q8TAD2, Q96PD4, Q9EQI6, Q9QXT6, Q9UHF5, A9XE49, Q8K4C5, Q8VHH8, Q9H293, Q9P0M4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
IL17B	up-regulates	IL17RB	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

463 predictions. Top by Δscore:

Variant	Effect	Δscore
5:149374611:C:CT	acceptor_gain	1.0000
5:149374612:A:T	acceptor_gain	1.0000
5:149374596:TGATG:T	acceptor_gain	0.9900
5:149374598:ATG:A	acceptor_gain	0.9900
5:149374598:ATGC:A	acceptor_loss	0.9900
5:149374599:TG:T	acceptor_gain	0.9900
5:149374601:C:CC	acceptor_gain	0.9900
5:149374601:C:T	acceptor_loss	0.9900
5:149376730:GCCTA:G	donor_loss	0.9900
5:149376731:CCTA:C	donor_loss	0.9900
5:149376732:CTACC:C	donor_loss	0.9900
5:149376733:TAC:T	donor_loss	0.9900
5:149376734:A:AT	donor_loss	0.9900
5:149377023:CAG:C	acceptor_gain	0.9900
5:149379200:CGTA:C	donor_loss	0.9900
5:149379203:A:AC	donor_gain	0.9900
5:149379203:ACCA:A	donor_loss	0.9900
5:149379204:C:CC	donor_gain	0.9900
5:149379204:C:CG	donor_loss	0.9900
5:149374597:GATG:G	acceptor_gain	0.9800
5:149374604:C:CT	acceptor_gain	0.9800
5:149376996:C:CT	acceptor_gain	0.9800
5:149376996:C:T	acceptor_gain	0.9800
5:149379204:CCAG:C	donor_gain	0.9800
5:149376997:A:T	acceptor_gain	0.9700
5:149379203:AC:A	donor_gain	0.9700
5:149379204:CC:C	donor_gain	0.9700
5:149379204:CCA:C	donor_gain	0.9700
5:149374598:ATGCT:A	acceptor_gain	0.9600
5:149374605:A:T	acceptor_gain	0.9600

AlphaMissense

1180 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:149376744:C:A	W101C	1.000
5:149376744:C:G	W101C	1.000
5:149374379:C:T	C178Y	0.999
5:149374492:G:C	S140R	0.999
5:149374492:G:T	S140R	0.999
5:149374494:T:G	S140R	0.999
5:149374550:C:G	C121S	0.999
5:149374551:A:T	C121S	0.999
5:149374378:G:C	C178W	0.998
5:149374380:A:G	C178R	0.998
5:149374385:C:G	C176S	0.998
5:149374386:A:G	C176R	0.998
5:149374386:A:T	C176S	0.998
5:149374535:C:G	C126S	0.998
5:149374535:C:T	C126Y	0.998
5:149374536:A:G	C126R	0.998
5:149374536:A:T	C126S	0.998
5:149374581:G:T	R111S	0.998
5:149376746:A:G	W101R	0.998
5:149376746:A:T	W101R	0.998
5:149376756:G:C	S97R	0.998
5:149376756:G:T	S97R	0.998
5:149376758:T:G	S97R	0.998
5:149374379:C:A	C178F	0.997
5:149374379:C:G	C178S	0.997
5:149374380:A:T	C178S	0.997
5:149374384:G:C	C176W	0.997
5:149374385:C:T	C176Y	0.997
5:149374388:C:T	G175D	0.997
5:149374549:G:C	C121W	0.997

dbSNP variants (sampled 300 via entrez): RS1000128387 (5:149375623 A>T), RS1000184978 (5:149402344 C>A,T), RS1000275686 (5:149389978 G>A), RS1000303963 (5:149400939 G>A), RS1000337766 (5:149395693 G>A), RS1000398400 (5:149397054 G>A), RS1000429253 (5:149395405 T>C), RS1000514062 (5:149403495 C>T), RS1000674304 (5:149397902 C>A,T), RS1000698034 (5:149383412 G>A), RS1000710811 (5:149390224 C>A,G,T), RS1000769893 (5:149383573 A>C), RS1001002003 (5:149378142 C>A,G,T), RS1001106924 (5:149386682 A>G), RS1001349194 (5:149395615 C>T)

Disease associations

OMIM: gene MIM:604627 | disease phenotypes: MIM:148300

GenCC curated gene-disease

Mondo (1): keratoconus 1 (MONDO:0007851)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007017_1	Serum bilirubin levels x Mediterranean diet adherence interaction in metabolic syndrome	3.000000e-08
GCST009302_9	Antipsychotic drug-induced weight gain in schizophrenia	1.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004570	bilirubin measurement
EFO:0008111	diet measurement
EFO:0004567	antipsychotic drug related weight gain

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563649	Keratoconus 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Asian ginseng	decreases reaction, increases expression	1
perfluorooctanoic acid	affects cotreatment, increases expression	1
aflatoxin B2	decreases methylation	1
perfluorooctane sulfonic acid	increases expression, affects cotreatment	1
perfluorohexanesulfonic acid	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	decreases methylation	1
Benzo(a)pyrene	increases methylation	1
Bleomycin	decreases expression	1
Diethylhexyl Phthalate	decreases reaction, increases expression	1
Rotenone	increases expression	1
Silicon Dioxide	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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