IL17D

Summary

IL17D (interleukin 17D, HGNC:5984) is a protein-coding gene on chromosome 13q12.11, encoding Interleukin-17D (Q8TAD2). Induces expression of IL6, CXCL8/IL8, and CSF2/GM-CSF from endothelial cells.

The protein encoded by this gene is a cytokine that shares the sequence similarity with IL17. The treatment of endothelial cells with this cytokine has been shown to stimulate the production of other cytokines including IL6, IL8 and CSF2/ GM-CSF. The increased expression of IL8 induced by this cytokine was found to be NF-kappa B-dependent.

Source: NCBI Gene 53342 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_001385224

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5984
Approved symbol	IL17D
Name	interleukin 17D
Location	13q12.11
Locus type	gene with protein product
Status	Approved
Aliases	IL-27, IL-17D, IL27, FLJ30846
Ensembl gene	ENSG00000172458
Ensembl biotype	protein_coding
OMIM	607587
Entrez	53342

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 nonsense_mediated_decay

ENST00000304920, ENST00000468605, ENST00000498088, ENST00000682841, ENST00000962835, ENST00000962836

RefSeq mRNA: 5 — MANE Select: NM_001385224 NM_001385221, NM_001385222, NM_001385223, NM_001385224, NM_138284

CCDS: CCDS9292

Canonical transcript exons

ENST00000682841 — 2 exons

Exon	Start	End
ENSE00001146420	20721636	20723098
ENSE00003920250	20703699	20704291

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 97.69.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3696 / max 117.7784, expressed in 305 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
134314	0.7215	195
134311	0.2278	98
134316	0.1871	23
134313	0.1742	80
134315	0.0296	13
134312	0.0294	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vastus lateralis	UBERON:0001379	97.69	gold quality
nucleus accumbens	UBERON:0001882	97.58	gold quality
medial globus pallidus	UBERON:0002477	97.51	gold quality
caudate nucleus	UBERON:0001873	97.49	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.49	gold quality
putamen	UBERON:0001874	97.48	gold quality
quadriceps femoris	UBERON:0001377	97.29	gold quality
biceps brachii	UBERON:0001507	97.19	gold quality
amygdala	UBERON:0001876	97.07	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.00	gold quality
globus pallidus	UBERON:0001875	96.89	gold quality
right frontal lobe	UBERON:0002810	96.84	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.83	gold quality
deltoid	UBERON:0001476	96.70	gold quality
spinal cord	UBERON:0002240	96.29	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.26	gold quality
hypothalamus	UBERON:0001898	96.14	gold quality
anterior cingulate cortex	UBERON:0009835	96.14	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.82	gold quality
skeletal muscle tissue	UBERON:0001134	95.67	gold quality
substantia nigra	UBERON:0002038	95.49	gold quality
prefrontal cortex	UBERON:0000451	95.28	gold quality
Ammon’s horn	UBERON:0001954	95.15	gold quality
lateral globus pallidus	UBERON:0002476	95.09	gold quality
tendon of biceps brachii	UBERON:0008188	94.98	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.81	gold quality
midbrain	UBERON:0001891	94.80	gold quality
temporal lobe	UBERON:0001871	94.75	gold quality
frontal cortex	UBERON:0001870	94.71	gold quality
neocortex	UBERON:0001950	94.60	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.75

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

31 targeting IL17D, 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-4795-3P	100.00	74.62	4024
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-4744	99.01	69.91	1581
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-6877-3P	98.98	65.83	560
HSA-MIR-6819-3P	98.95	65.57	572
HSA-MIR-1245B-3P	98.01	68.91	1387
HSA-MIR-4637	97.69	68.14	632
HSA-MIR-6781-3P	97.44	66.85	970
HSA-MIR-2682-3P	97.10	66.16	840
HSA-MIR-873-3P	96.84	66.09	786
HSA-MIR-324-5P	95.68	65.20	560
HSA-MIR-3672	94.46	65.67	646

Literature-anchored findings (GeneRIF, showing 9)

• IL-17D stimulates production of cytokines in endothelial cells in vitro and suppresses proliferation of myeloid progenitors in colony formation assays. (PMID:12097364)
• IL-27 priming results in enhanced lipopolysaccharide-induced IL-6, tumor necrosis factor (TNF)-alpha, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta expression in human primary monocytes. (PMID:22156348)
• These experiments were designed to investigate the effects of IL-17 upon the phenotype and function of human Natural Killer (NK) cells. (PMID:23490420)
• Utilizing gene microarray analysis, authors found the cytokine interleukin 17D (IL-17D) was highly expressed in certain unedited tumors. (PMID:24794441)
• Nrf2 Induces IL-17D to mediate tumor and virus surveillance. (PMID:27545889)
• Study of the expression of IL-17 provides theoretical support for the clinical treatment and prognosis prediction of ovarian epithelial tumor. (PMID:28685546)
• Nuclear factor erythroid 2-related factor 2 potentiates the generation of inflammatory cytokines by intestinal epithelial cells during hyperoxia by inducing the expression of interleukin 17D. (PMID:34023435)
• Interleukin-17D promotes lung cancer progression by inducing tumor-associated macrophage infiltration via the p38 MAPK signaling pathway. (PMID:35939336)
• Interleukin-17D produced by alveolar epithelial type II cells alleviates LPS-induced acute lung injury via the Nrf2 pathway. (PMID:37708335)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	il17d	ENSDARG00000010700
mus_musculus	Il17d	ENSMUSG00000050222
rattus_norvegicus	Il17d	ENSRNOG00000079865

Paralogs (5): IL17A (ENSG00000112115), IL17F (ENSG00000112116), IL17C (ENSG00000124391), IL17B (ENSG00000127743), IL25 (ENSG00000166090)

Protein

Protein identifiers

Interleukin-17D — Q8TAD2 (reviewed: Q8TAD2)

Alternative names: Interleukin-27

All UniProt accessions (3): A0A087WW17, A0A087WWZ4, Q8TAD2

UniProt curated annotations — full annotation on UniProt →

Function. Induces expression of IL6, CXCL8/IL8, and CSF2/GM-CSF from endothelial cells.

Subcellular location. Secreted.

Tissue specificity. Expressed preferentially in adipose, skeletal muscle and CNS.

Similarity. Belongs to the IL-17 family.

RefSeq proteins (5): NP_001372150, NP_001372151, NP_001372152, NP_001372153, NP_612141 (=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): glycosylation site 2, signal peptide 1, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAD2-F1	78.81	0.52

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (2): 68, 181

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 221 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, CREL_01, GCM_MAP4K4, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE

GO Biological Process (7): inflammatory response (GO:0006954), positive regulation of granulocyte macrophage colony-stimulating factor production (GO:0032725), positive regulation of interleukin-6 production (GO:0032755), positive regulation of interleukin-8 production (GO:0032757), positive regulation of cytokine production involved in inflammatory response (GO:1900017), negative regulation of hemopoiesis (GO:1903707), signal transduction (GO:0007165)

GO Molecular Function (3): cytokine activity (GO:0005125), protein homodimerization activity (GO:0042803), receptor ligand activity (GO:0048018)

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
positive regulation of cytokine production	4
defense response	1
granulocyte macrophage colony-stimulating factor production	1
regulation of granulocyte macrophage colony-stimulating factor production	1
positive regulation of protein metabolic process	1
interleukin-6 production	1
regulation of interleukin-6 production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
cytokine production involved in inflammatory response	1
regulation of cytokine production involved in inflammatory response	1
negative regulation of immune system process	1
negative regulation of cell development	1
hemopoiesis	1
negative regulation of multicellular organismal process	1
regulation of hemopoiesis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
receptor ligand activity	1
identical protein binding	1
protein dimerization activity	1
signaling receptor binding	1
signal transduction	1
signaling receptor activator activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

550 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL17D	IL25	Q9H293	976
IL17D	IL17RB	Q9NRM6	944
IL17D	IL17RA	Q96F46	886
IL17D	IL17RC	Q8NAC3	818
IL17D	IL17RE	Q8NFR9	817
IL17D	IL17RD	Q8NFM7	784
IL17D	IL17B	Q9UHF5	641
IL17D	CD4	P01730	626
IL17D	IL17C	Q9P0M4	563
IL17D	CD93	Q9NPY3	542
IL17D	IL6R	P08887	531
IL17D	CSF2	P04141	530
IL17D	IL22	Q9GZX6	507
IL17D	SORBS2	O94875	481
IL17D	IL6	P05231	473

IntAct

3 interactions, top by confidence:

A	B	Type	Score
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
IL17D	CCNH	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): HSP90AA4P (Affinity Capture-MS), CCNH (Affinity Capture-MS), IL17D (Affinity Capture-MS), IL17D (Affinity Capture-MS)

ESM2 similar proteins: D3YZZ2, E7ERA6, F2Z333, H3BV60, O00292, O18796, O43508, O43612, O54907, O55232, O55241, O60391, O75462, O75610, O77668, O95633, O95685, P13224, P41155, P56717, Q02833, Q06643, Q14626, Q1LZB9, Q2TBM7, Q4V892, Q5RF19, Q5TM22, Q6IA17, Q6UXT9, Q6ZMM2, Q862Z7, Q86VR8, Q86YD3, Q8BQB4, Q8NBV8, Q8TAD2, Q99640, Q99MF4, Q9BZR6

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

586 predictions. Top by Δscore:

Variant	Effect	Δscore
13:20703453:A:T	donor_gain	1.0000
13:20704289:CAGG:C	donor_loss	1.0000
13:20704292:GTGAG:G	donor_loss	1.0000
13:20703452:G:GT	donor_gain	0.9900
13:20704292:G:GG	donor_gain	0.9900
13:20721634:A:AG	acceptor_gain	0.9900
13:20721635:G:GA	acceptor_gain	0.9900
13:20721635:GA:G	acceptor_gain	0.9900
13:20721635:GAAT:G	acceptor_gain	0.9900
13:20703464:G:GT	donor_gain	0.9800
13:20705245:G:T	donor_gain	0.9800
13:20720672:G:GT	donor_gain	0.9800
13:20720730:GGACT:G	donor_gain	0.9800
13:20721630:CTGCA:C	acceptor_loss	0.9800
13:20721631:TGCA:T	acceptor_loss	0.9800
13:20721632:GCAG:G	acceptor_loss	0.9800
13:20721633:CA:C	acceptor_loss	0.9800
13:20721634:AGA:A	acceptor_loss	0.9800
13:20720176:G:T	donor_gain	0.9700
13:20721635:GAA:G	acceptor_gain	0.9700
13:20721635:GAATC:G	acceptor_gain	0.9700
13:20703441:CCGGG:C	donor_loss	0.9600
13:20703442:CGGG:C	donor_loss	0.9600
13:20703443:GG:G	donor_gain	0.9600
13:20703444:GG:G	donor_gain	0.9600
13:20703444:GGTAC:G	donor_loss	0.9600
13:20703445:GTA:G	donor_loss	0.9600
13:20703446:TA:T	donor_loss	0.9600
13:20706466:GGCC:G	donor_gain	0.9600
13:20705233:G:GT	donor_gain	0.9500

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000010430 (13:20713673 C>T), RS1000238343 (13:20707347 A>C,G), RS1000275110 (13:20722084 C>CTT), RS1000297552 (13:20719785 C>A,T), RS1000536640 (13:20703955 C>T), RS1000568853 (13:20707022 G>A), RS1000678006 (13:20701451 C>T), RS1000949925 (13:20703718 C>G), RS1000974312 (13:20708846 A>C), RS1001204106 (13:20716185 A>G), RS1001493198 (13:20699621 G>C,T), RS1001553182 (13:20704180 TGG>T), RS1001574641 (13:20713252 G>A), RS1001578025 (13:20717054 G>A), RS1001714253 (13:20706864 G>A)

Disease associations

OMIM: gene MIM:607587 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002456_1	PR segment duration	2.000000e-08
GCST010796_25	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-14
GCST010796_76	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-10
GCST010796_77	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-12
GCST010796_78	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-12
GCST010796_79	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005095	PR segment
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression, decreases expression	5
Benzo(a)pyrene	affects methylation, increases methylation	2
Smoke	decreases expression	2
Tretinoin	increases expression	2
bisphenol A	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
2-tert-butylhydroquinone	increases expression, increases reaction	1
CGP 52608	affects binding, increases reaction	1
belinostat	decreases expression	1
Temozolomide	increases expression	1
Vorinostat	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Endosulfan	increases expression	1
Estradiol	increases expression	1
Oxygen	increases expression, increases reaction	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1
Tunicamycin	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases expression	1

Clinical trials (associated diseases)

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