IL17RA

Summary

IL17RA (interleukin 17 receptor A, HGNC:5985) is a protein-coding gene on chromosome 22q11.1, encoding Interleukin-17 receptor A (Q96F46). Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity.

Interleukin 17A (IL17A) is a proinflammatory cytokine secreted by activated T-lymphocytes. It is a potent inducer of the maturation of CD34-positive hematopoietic precursors into neutrophils. The transmembrane protein encoded by this gene (interleukin 17A receptor; IL17RA) is a ubiquitous type I membrane glycoprotein that binds with low affinity to interleukin 17A. Interleukin 17A and its receptor play a pathogenic role in many inflammatory and autoimmune diseases such as rheumatoid arthritis. Like other cytokine receptors, this receptor likely has a multimeric structure. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 23765 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 51 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 35
• Clinical variants (ClinVar): 990 total — 17 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 49
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_014339

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5985
Approved symbol	IL17RA
Name	interleukin 17 receptor A
Location	22q11.1
Locus type	gene with protein product
Status	Approved
Aliases	hIL-17R, IL-17RA, CDw217, CD217
Ensembl gene	ENSG00000177663
Ensembl biotype	protein_coding
OMIM	605461
Entrez	23765

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000319363, ENST00000459971, ENST00000477874, ENST00000612619, ENST00000694948, ENST00000694949, ENST00000694950, ENST00000694951, ENST00000940705, ENST00000962147

RefSeq mRNA: 2 — MANE Select: NM_014339 NM_001289905, NM_014339

CCDS: CCDS13739, CCDS77645

Canonical transcript exons

ENST00000319363 — 13 exons

Exon	Start	End
ENSE00001239593	17107727	17107768
ENSE00001239606	17104726	17104810
ENSE00001239625	17105853	17105954
ENSE00001239646	17103494	17103577
ENSE00001239653	17102139	17102302
ENSE00001239658	17101996	17102043
ENSE00001239660	17100355	17100481
ENSE00001239675	17097062	17097086
ENSE00001656252	17105591	17105602
ENSE00001886659	17108307	17115693
ENSE00003520443	17098775	17098887
ENSE00003629316	17097797	17097943
ENSE00003897468	17085000	17085229

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 95.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.8435 / max 3212.9589, expressed in 1813 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190954	32.7973	1810
190955	11.0461	1335

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	95.79	gold quality
monocyte	CL:0000576	95.21	gold quality
leukocyte	CL:0000738	94.99	gold quality
mononuclear cell	CL:0000842	94.97	gold quality
trabecular bone tissue	UBERON:0002483	93.89	gold quality
granulocyte	CL:0000094	92.85	gold quality
bone marrow	UBERON:0002371	91.53	gold quality
bone marrow cell	CL:0002092	91.05	gold quality
tendon of biceps brachii	UBERON:0008188	90.14	gold quality
medial globus pallidus	UBERON:0002477	88.59	gold quality
globus pallidus	UBERON:0001875	87.28	gold quality
ileal mucosa	UBERON:0000331	86.80	silver quality
secondary oocyte	CL:0000655	86.41	gold quality
thymus	UBERON:0002370	85.42	gold quality
pancreatic ductal cell	CL:0002079	85.28	silver quality
inferior vagus X ganglion	UBERON:0005363	85.20	gold quality
stromal cell of endometrium	CL:0002255	84.86	gold quality
pericardium	UBERON:0002407	84.78	gold quality
lateral globus pallidus	UBERON:0002476	84.33	gold quality
lower lobe of lung	UBERON:0008949	84.28	gold quality
jejunal mucosa	UBERON:0000399	83.90	gold quality
spleen	UBERON:0002106	83.76	gold quality
superficial temporal artery	UBERON:0001614	82.63	silver quality
subthalamic nucleus	UBERON:0001906	82.34	gold quality
oocyte	CL:0000023	82.30	gold quality
layer of synovial tissue	UBERON:0007616	81.90	gold quality
tongue squamous epithelium	UBERON:0006919	81.65	gold quality
upper lobe of lung	UBERON:0008948	81.25	gold quality
upper lobe of left lung	UBERON:0008952	81.13	gold quality
descending thoracic aorta	UBERON:0002345	81.11	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	20.41
E-ANND-3	yes	19.06
E-MTAB-9067	yes	13.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

141 targeting IL17RA, 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-8485	100.00	77.57	4731
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-374C-5P	99.80	72.06	2910

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Expression, modulation and signalling of IL-17 receptor in fibroblast-like synoviocytes of patients with rheumatoid arthritis (PMID:11966773)
• cell membrane IL-17R is required for signaling by both IL-17A and IL-17F (PMID:15972674)
• In this JEG-3 cell model of human trophoblast, the IL-17 receptor may have a regulatory role in trophoblast invasion. (PMID:16533341)
• The biologic activity of IL-17 is dependent on a complex composed of receptors IL-17RA and IL-17RC. (PMID:16785495)
• Both IL-17 and IL-17R displayed specific bands in nasal polyps and turbinates, but the bands of IL-17 and IL-17R in nasal polyps were stronger than those in turbinates. (PMID:16805377)
• IL-17 may have an important role in the occurrence of nasal polyps by specific combination with IL-17R and over-expression in nasal polyps. (PMID:16874957)
• This study, for the first time, reveals a possible molecular mechanism that the initiation of the IL-17F/IL-17R signaling pathway requires the receptor ubiquitination by TRAF6. (PMID:17346928)
• structure-function analysis of a IL-17 superfamily receptor reveals important differences in IL-17RA compared with IL-1/TLR receptors (PMID:17456598)
• IL-17 contributes to osteoclastic bone resoption in RA patients. (PMID:17876645)
• IL-17A-induced IL-6, IL-8, and CCL20 secretion was dependent on both IL-17RA and IL-17RC, which are overexpressed in RA patients. (PMID:18097068)
• IL-2 and IL-15 differentially regulate PI3K and IL-17RA (PMID:18348982)
• Interleukin (IL)-17A activity is inhibited by the IL-17RA receptor, and a combination of soluble IL-17RA/IL-17RC receptors is required for inhibition of heterodimeric IL-17F/IL-17A activity. (PMID:18684971)
• IL-17RA plays a functional role in the human IL-25 receptor complex in vitro that is independent of IL-17A. (PMID:18768888)
• significant association between Crohn disease and the widely replicated IL23R variants is only seen in the presence of IL17A or IL17RA variants (PMID:19235914)
• IL-17 receptor signaling inhibits C/EBPbeta by sequential phosphorylation of the regulatory 2 domain. (PMID:19244213)
• an extended SEFIR domain is required for il-17RA-mediated signal transduction. (PMID:20729198)
• Human periodontal ligament fibroblasts are a target of Th17, and that IL-17 appears to up-regulate the expression of IL-23 p19 via a homeostatic mechanism involving Akt-, p38 MAPK-, and ERK 1/2-dependent NF-kappaB signalling versus the JNK/AP-1 pathway. (PMID:21145111)
• mRNA levels of IL-17, IL-17R and MMP-9 were also higher in the invasive group than in the non-invasive group in human pituitary adenomas. (PMID:21279695)
• IL-17/IL-17RA signaling plays an important role in myocardial collagen metabolism in hypertension-induced diastolic dysfunction. (PMID:21530504)
• Blockage of IL-17RA with an anti-IL-17RA antibody inhibited the production of IL-6, IL-8, and MMP-3; demonstrate the functional significance of IL-17RA in psoriatic arthritis (PMID:21894442)
• IFN-alpha could be associated with the expansion of IL-7Ralpha(low) CD45RA(+) EM CD8(+) T cells in the CMV-uninfected elderly (PMID:22484243)
• Data show that IL-17RA, IL-17RC, IL-22R1, ERK1/2 MAPK and NF-kappaB pathways are involved in Th17 cytokine-induced proliferation. (PMID:22898922)
• Our results might be helpful for explaining the missing heritability of the psoriasis due to epistasis and provide a deep insight into the important role of the IL23/Th17 pathway in the pathogenesis of psoriasis. (PMID:22909235)
• Il-17R SNPs were not associated with psoriatic arthritis susceptibility in northern Italians. (PMID:22955875)
• Two polymorphisms within the IL17E and IL17RA genes are associated with ESRD independent of age and sex. (PMID:23147652)
• IL-17A/IL-17RA interaction promoted the metastasis of OS in nude mice. (PMID:23192273)
• Data suggest that the interleukin 17 receptor A (IL17RA) minor alleles of the three single nucleotide polymorphisms (SNP) may decrease the risk of Aspirin Exacerbated Respiratory Disease (AERD) via attenuation of IL17RA gene expression. (PMID:23220496)
• protein levels of IL-17 and IL-17R positively correlated with the frequency of seizures in focal cortical dysplasias patients patients. (PMID:23334598)
• Our data indicates that serum IL-17 levels are significantly increased in intractable Graves disease and affected thyrocytes show functional IL-17R expression. (PMID:23501056)
• crystal structures of homodimeric IL-17A and its complex with IL-17RA, are reported. (PMID:23695682)
• polymorphism of IL-17R plays no significant role in incidence of chronic periodontitis and Periimplantitis. (PMID:23852838)
• Data show that the interleukin (IL)-17 receptor IL-17RA variant is generated by spliced out of exon 11 encoding the transmembrane region in a variety of tissues. (PMID:24084331)
• Whereas no association was found between the alternative splicing SNP, rs6897932, and multiple sclerosis, a significant link was found between the promoter single nucleotide polymorphism, rs11567685, and the disease. (PMID:24166352)
• The increased IL-25 levels in plasma and the expression of IL-17RA and IL-17RB on eosinophils in allergic asthma patients suggests that IL-25 may activate eosinophils during allergic inflammation. (PMID:24247484)
• Genetic variation in interleukin-17 receptor A is functionally associated with chronic rejection after lung transplantation. (PMID:24263024)
• IL17-dependent retinal degeneration in a mouse model of focal retinal degeneration can be prevented by gene therapy with adeno-associated virus vector encoding soluble IL17 receptor (PMID:24780906)
• Interleukin-17 receptor A crystal structure shows that the downstream motif of IL-17RA SEFIR together with helix alpha C could provide a composite ligand-binding surface for recruiting Act1 during IL-17 signaling. (PMID:24816115)
• IL-17R was almost exclusively expressed by endothelial cells, not by myeloma cells in the masses of skeletal extramedullary disease patients. (PMID:24916639)
• IL17RA polymorphisms, but not those of IL17, can influence both the development and the bilaterality of papillary thyroid carcinoma (PMID:25484349)
• genetic polymorphism is associated with a reduced renal filtration rate, and with the risk of developing end stage renal disease in healthy elderly from Spain (PMID:25636567)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Il17ra	ENSMUSG00000002897
rattus_norvegicus	Il17ra	ENSRNOG00000011153

Paralogs (4): IL17RB (ENSG00000056736), IL17RD (ENSG00000144730), IL17RE (ENSG00000163701), IL17RC (ENSG00000163702)

Protein

Protein identifiers

Interleukin-17 receptor A — Q96F46 (reviewed: Q96F46)

Alternative names: CDw217

All UniProt accessions (3): A0A8Q3WK71, A0A8Q3WKC6, Q96F46

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity. Receptor for IL17A. Receptor for IL17F. Binds to IL17A with higher affinity than to IL17F. Binds IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RC. Also binds heterodimers formed by IL17A and IL17F as part of a heterodimeric complex with IL17RC. Cytokine binding triggers homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter, leading to TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways, ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation. Involved in antimicrobial host defense primarily promoting neutrophil activation and recruitment at infection sites to destroy extracellular bacteria and fungi. In secondary lymphoid organs, contributes to germinal center formation by regulating the chemotactic response of B cells to CXCL12 and CXCL13, enhancing retention of B cells within the germinal centers, B cell somatic hypermutation rate and selection toward plasma cells. Plays a role in the maintenance of the integrity of epithelial barriers during homeostasis and pathogen infection. Stimulates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers. Involved in antiviral host defense through various mechanisms. Enhances immunity against West Nile virus by promoting T cell cytotoxicity. Contributes to Influenza virus clearance by driving the differentiation of B-1a B cells, providing for production of virus-specific IgM antibodies at first line of host defense. Receptor for IL17C as part of a heterodimeric complex with IL17RE. (Microbial infection) Receptor for SARS coronavirus-2/SARS-CoV-2 virus protein ORF8, leading to IL17 pathway activation and an increased secretion of pro-inflammatory factors through activating NF-kappa-B signaling pathway.

Subunit / interactions. Forms heterodimers with IL17RC; the heterodimer binds IL17A and IL17F homodimers as well as the heterodimer formed by IL17A and IL17F. Forms complexes with 2:1 binding stoichiometry: two receptor chains for one interleukin molecule. IL17A homodimer preferentially drives the formation of IL17RA-IL17RC heterodimeric receptor complex, whereas IL17F homodimer forms predominantly complexes with IL17RC homodimer. IL17A homodimer adopts an asymmetrical ternary structure with one IL17RA molecule, allowing for high affinity interactions of one IL17A monomer with one IL17RA molecule (via D1 and D2 domains), while disfavoring binding of a second IL17RA molecule on the other IL17A monomer. IL17A-IL17F forms complexes with IL17RA-IL17RC, but with lower affinity when compared to IL17A homodimer. IL17RA chain cannot distinguish between IL17A and IL17F molecules, potentially enabling the formation of topologically distinct complexes. Interacts with TRAF3IP2. Forms heterodimers with IL17RE; the heterodimer binds IL17C. (Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 virus protein ORF8.

Subcellular location. Cell membrane Secreted.

Tissue specificity. Widely expressed.

Post-translational modifications. Glycosylated.

Disease relevance. Immunodeficiency 51 (IMD51) [MIM:613953] A primary immunodeficiency disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Soluble isoform lacking the transmembrane segment.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96F46-1	1	yes
Q96F46-2	2

RefSeq proteins (2): NP_001276834, NP_055154* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013568	SEFIR_dom	Domain
IPR032356	IL17R_A/B_N	Domain
IPR038683	IL17RA/B_FnIII-like_1_sf	Homologous_superfamily
IPR039465	IL-17_rcpt-like	Family
IPR043046	IL17RA/B_FnIII-like_2_sf	Homologous_superfamily

Pfam: PF08357, PF16556, PF16578

UniProt features (78 total): strand 23, helix 18, glycosylation site 7, turn 7, disulfide bond 6, sequence variant 4, modified residue 2, topological domain 2, region of interest 2, compositionally biased region 2, signal peptide 1, chain 1, splice variant 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
5N9B	X-RAY DIFFRACTION	1.9
4NUX	X-RAY DIFFRACTION	2.29
7UWM	ELECTRON MICROSCOPY	2.5
9OT1	ELECTRON MICROSCOPY	3
7UWN	ELECTRON MICROSCOPY	3.01
4HSA	X-RAY DIFFRACTION	3.15
3JVF	X-RAY DIFFRACTION	3.3
5NAN	X-RAY DIFFRACTION	3.3
7UWL	ELECTRON MICROSCOPY	3.7
7ZAN	X-RAY DIFFRACTION	5.06

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96F46-F1	70.33	0.37

Functional residue map

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

Post-translational modifications (2): 708, 736

Disulfide bonds (6): 43–50, 57–126, 185–196, 245–276, 277–303, 290–294

Glycosylation sites (7): 49, 54, 67, 206, 225, 242, 265

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-448424	Interleukin-17 signaling
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses

MSigDB gene sets: 371 (showing top): GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_KERATINOCYTE_PROLIFERATION, GOBP_GROWTH, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GAURNIER_PSMD4_TARGETS, BROWNE_HCMV_INFECTION_12HR_UP, BILD_SRC_ONCOGENIC_SIGNATURE, HUMMERICH_SKIN_CANCER_PROGRESSION_UP, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS

GO Biological Process (20): inflammatory response (GO:0006954), cell surface receptor signaling pathway (GO:0007166), response to virus (GO:0009615), protein catabolic process (GO:0030163), positive regulation of interleukin-13 production (GO:0032736), positive regulation of interleukin-23 production (GO:0032747), positive regulation of interleukin-5 production (GO:0032754), positive regulation of interleukin-6 production (GO:0032755), interleukin-17A-mediated signaling pathway (GO:0038173), innate immune response (GO:0045087), positive regulation of inflammatory response (GO:0050729), defense response to fungus (GO:0050832), granulocyte chemotaxis (GO:0071621), fibroblast activation (GO:0072537), T-helper 17 type immune response (GO:0072538), interleukin-17-mediated signaling pathway (GO:0097400), positive regulation of cytokine production involved in inflammatory response (GO:1900017), positive regulation of chemokine (C-X-C motif) ligand 1 production (GO:2000340), adaptive immune response (GO:0002250), immune system process (GO:0002376)

GO Molecular Function (3): signaling receptor binding (GO:0005102), interleukin-17 receptor activity (GO:0030368), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Interleukins	1
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of cytokine production	5
defense response	2
cytokine-mediated signaling pathway	2
immune response	2
cellular anatomical structure	2
signal transduction	1
response to other organism	1
macromolecule catabolic process	1
protein metabolic process	1
interleukin-13 production	1
regulation of interleukin-13 production	1
interleukin-23 production	1
regulation of interleukin-23 production	1
interleukin-5 production	1
regulation of interleukin-5 production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
defense response to symbiont	1
inflammatory response	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
response to fungus	1
leukocyte chemotaxis	1
granulocyte migration	1
cell activation	1
adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
cellular response to interleukin-17	1
cytokine production involved in inflammatory response	1
regulation of cytokine production involved in inflammatory response	1
positive regulation of chemokine production	1
chemokine (C-X-C motif) ligand 1 production	1
regulation of chemokine (C-X-C motif) ligand 1 production	1
biological_process	1
protein binding	1
cytokine receptor activity	1
interleukin-17 binding	1
binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1964 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL17RA	IL17A	Q16552	999
IL17RA	IL17F	Q96PD4	999
IL17RA	IL25	Q9H293	997
IL17RA	IL17RE	Q8NFR9	996
IL17RA	IL17RC	Q8NAC3	990
IL17RA	IL17RB	Q9NRM6	988
IL17RA	IL17C	Q9P0M4	982
IL17RA	IL17RD	Q8NFM7	982
IL17RA	IL17B	Q9UHF5	963
IL17RA	TRAF3IP2	O43734	892
IL17RA	IL17D	Q8TAD2	886
IL17RA	IL6	P05231	844
IL17RA	IL22RA1	Q8N6P7	834
IL17RA	TRAF3	Q13114	826
IL17RA	IL22	Q9GZX6	823

IntAct

89 interactions, top by confidence:

A	B	Type	Score
IL17RA	IL17A	psi-mi:“MI:0407”(direct interaction)	0.810
IL17A	IL17RA	psi-mi:“MI:0407”(direct interaction)	0.810
IL17RA	IL17A	psi-mi:“MI:0915”(physical association)	0.810
IL17RA		psi-mi:“MI:0915”(physical association)	0.620
IL17RB	IL17RA	psi-mi:“MI:0403”(colocalization)	0.600
IL17RA	IL17RB	psi-mi:“MI:0407”(direct interaction)	0.600
OS9	AGRN	psi-mi:“MI:0914”(association)	0.530
PRG3	ZNF324	psi-mi:“MI:0914”(association)	0.530
IL17A	IL2	psi-mi:“MI:0914”(association)	0.530
	PLOD2	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
DNASE2B	ARSA	psi-mi:“MI:0914”(association)	0.530
CMA1	MANBA	psi-mi:“MI:0914”(association)	0.530
IGFBP4	MYCBP2	psi-mi:“MI:0914”(association)	0.530
IL17RA	IL25	psi-mi:“MI:0915”(physical association)	0.490
IL17RA	IL17F	psi-mi:“MI:0407”(direct interaction)	0.440
IL17RE	IL17RA	psi-mi:“MI:0915”(physical association)	0.400
IL17RA	IL17RE	psi-mi:“MI:0915”(physical association)	0.400
SUSD4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
IL17RA	DDX11L8	psi-mi:“MI:0914”(association)	0.350
SLAMF1	RTCA	psi-mi:“MI:0914”(association)	0.350
LYZL1	MANBA	psi-mi:“MI:0914”(association)	0.350
DNASE2B		psi-mi:“MI:0914”(association)	0.350
IDS	COCH	psi-mi:“MI:0914”(association)	0.350

BioGRID (173): IL17RA (Affinity Capture-Western), IL17RA (Affinity Capture-Western), IL17RA (Affinity Capture-Western), IL17RA (Affinity Capture-MS), IL17RA (Affinity Capture-MS), IL17RA (Affinity Capture-MS), KIAA0586 (Affinity Capture-MS), RPS6KA3 (Affinity Capture-MS), RPS6KA2 (Affinity Capture-MS), RPS6KA1 (Affinity Capture-MS), TUBB1 (Affinity Capture-MS), DDX11 (Affinity Capture-MS), SIK2 (Affinity Capture-MS), PLCH1 (Affinity Capture-MS), PLEKHA5 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RQ45, A0A1B0GWB2, A2A9T0, A6QPA0, A7MCY6, D3ZFB6, E9PUL5, E9Q0B3, F5GYI3, F5H4A9, J3QNX5, O70142, P0C1G7, P81408, P97764, P98077, Q148V8, Q15654, Q2KI80, Q3SX26, Q3SZL6, Q4V9L6, Q5FVJ4, Q5FW56, Q5RAC1, Q5T7N3, Q6DG50, Q6PAJ3, Q6PJ61, Q6ZMQ8, Q6ZNR0, Q6ZRV2, Q75VX8, Q7Z6L0, Q86UK7, Q86VE0, Q8BGW2, Q8BRJ3, Q8BX43, Q8C0R7

Diamond homologs: Q60943, Q96F46, Q7T2L7, Q8JZL1, Q8NFM7, Q8QHJ9

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
IL17RA	“form complex”	“IL17R complex”	binding
GSK3B	“down-regulates quantity by destabilization”	IL17RA	phosphorylation
GSK3A	“down-regulates quantity by destabilization”	IL17RA	phosphorylation
GSK3B	“down-regulates quantity”	IL17RA	phosphorylation
IL17A	up-regulates	IL17RA	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 107 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Interleukin-17 signaling	6	22.1×	8e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	11
Uncertain significance	497
Likely benign	332
Benign	73

Top pathogenic / likely-pathogenic (28)

Variant ID	HGVS	Classification
1375868	NM_014339.7(IL17RA):c.213dup (p.Ser72fs)	Pathogenic
1386866	NM_014339.7(IL17RA):c.186G>A (p.Trp62Ter)	Pathogenic
2000048	NM_014339.7(IL17RA):c.205del (p.Thr69fs)	Pathogenic
2085281	NM_014339.7(IL17RA):c.680_681insG (p.Thr228fs)	Pathogenic
2794701	NM_014339.7(IL17RA):c.185G>A (p.Trp62Ter)	Pathogenic
2998290	NM_014339.7(IL17RA):c.705del (p.Ser236fs)	Pathogenic
30486	NM_014339.7(IL17RA):c.850C>T (p.Gln284Ter)	Pathogenic
372204	NM_014339.7(IL17RA):c.1302_1318dup (p.Asn440fs)	Pathogenic
372205	NM_014339.7(IL17RA):c.1159G>A (p.Asp387Asn)	Pathogenic
372206	NM_014339.7(IL17RA):c.196C>T (p.Arg66Ter)	Pathogenic
372207	NM_014339.7(IL17RA):c.268del (p.Leu90fs)	Pathogenic
372208	NM_014339.7(IL17RA):c.769_773del (p.Pro257fs)	Pathogenic
3722419	NM_014339.7(IL17RA):c.51del (p.Leu18fs)	Pathogenic
3727635	NM_014339.7(IL17RA):c.650dup (p.Arg218fs)	Pathogenic
580706	NM_014339.7(IL17RA):c.787C>T (p.Arg263Ter)	Pathogenic
649522	NM_014339.7(IL17RA):c.166_169dup (p.Cys57fs)	Pathogenic
857687	NM_014339.7(IL17RA):c.233del (p.Ile78fs)	Pathogenic
1067524	NM_014339.7(IL17RA):c.163+2T>C	Likely pathogenic
1518224	NM_014339.7(IL17RA):c.598+1G>T	Likely pathogenic
1691222	NM_014339.7(IL17RA):c.1173C>G (p.Tyr391Ter)	Likely pathogenic
2671780	NM_014339.7(IL17RA):c.805_808del (p.Thr269fs)	Likely pathogenic
3075957	NM_014339.7(IL17RA):c.599-1G>A	Likely pathogenic
3235884	NM_014339.7(IL17RA):c.292T>C (p.Trp98Arg)	Likely pathogenic
3362564	NM_014339.7(IL17RA):c.721del (p.Glu241fs)	Likely pathogenic
3362583	NM_014339.7(IL17RA):c.112_119del (p.His38fs)	Likely pathogenic
3658695	NM_014339.7(IL17RA):c.931+2T>G	Likely pathogenic
4849413	NM_014339.7(IL17RA):c.139-2_139-1del	Likely pathogenic
578680	NM_014339.7(IL17RA):c.310+2T>C	Likely pathogenic

SpliceAI

2560 predictions. Top by Δscore:

Variant	Effect	Δscore
22:17085335:G:GT	donor_gain	1.0000
22:17097286:A:T	donor_gain	1.0000
22:17097318:A:T	donor_gain	1.0000
22:17097787:T:TA	acceptor_gain	1.0000
22:17097788:G:A	acceptor_gain	1.0000
22:17097791:T:A	acceptor_gain	1.0000
22:17097793:CCAG:C	acceptor_loss	1.0000
22:17097795:A:C	acceptor_loss	1.0000
22:17097796:G:GA	acceptor_loss	1.0000
22:17097939:AGACG:A	donor_gain	1.0000
22:17097940:GACG:G	donor_gain	1.0000
22:17097940:GACGG:G	donor_gain	1.0000
22:17097941:ACG:A	donor_gain	1.0000
22:17097942:CG:C	donor_gain	1.0000
22:17097942:CGGT:C	donor_loss	1.0000
22:17097943:GG:G	donor_gain	1.0000
22:17097944:G:GA	donor_loss	1.0000
22:17097944:G:GG	donor_gain	1.0000
22:17097945:T:G	donor_loss	1.0000
22:17098770:T:A	acceptor_gain	1.0000
22:17098773:A:AG	acceptor_gain	1.0000
22:17098774:G:GT	acceptor_gain	1.0000
22:17098774:GC:G	acceptor_gain	1.0000
22:17098774:GCC:G	acceptor_gain	1.0000
22:17098774:GCCA:G	acceptor_gain	1.0000
22:17098884:GCGG:G	donor_gain	1.0000
22:17098886:GG:G	donor_gain	1.0000
22:17098887:GG:G	donor_gain	1.0000
22:17098888:GTAAG:G	donor_loss	1.0000
22:17098889:T:A	donor_loss	1.0000

AlphaMissense

5650 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:17097925:T:A	W98R	0.997
22:17097925:T:C	W98R	0.997
22:17102149:G:C	W203C	0.997
22:17102149:G:T	W203C	0.997
22:17100413:T:A	V161D	0.996
22:17097927:G:C	W98C	0.995
22:17097927:G:T	W98C	0.995
22:17102147:T:A	W203R	0.994
22:17102147:T:C	W203R	0.994
22:17108403:T:A	V395D	0.994
22:17108421:T:C	F401S	0.994
22:17108725:C:G	C502W	0.994
22:17097842:C:A	P70H	0.993
22:17098777:A:C	S105R	0.993
22:17098779:C:A	S105R	0.993
22:17098779:C:G	S105R	0.993
22:17108360:T:A	W381R	0.993
22:17108360:T:C	W381R	0.993
22:17108503:G:C	W428C	0.993
22:17108503:G:T	W428C	0.993
22:17108562:C:T	S448F	0.993
22:17098778:G:T	S105I	0.992
22:17098856:T:C	F131S	0.992
22:17108550:T:A	I444N	0.992
22:17108581:G:C	K454N	0.992
22:17108581:G:T	K454N	0.992
22:17108714:T:G	Y499D	0.992
22:17100362:T:C	F144S	0.990
22:17108369:T:G	Y384D	0.990
22:17108518:G:C	K433N	0.990

dbSNP variants (sampled 300 via entrez): RS1000069035 (22:17093070 GTT>G,GT,GTTT,GTTTT), RS1000187578 (22:17085931 T>G), RS1000477102 (22:17113128 A>T), RS1000736022 (22:17102859 A>G), RS1000785795 (22:17112917 C>T), RS1000790264 (22:17097539 C>G), RS1000981984 (22:17085840 CG>C), RS1000987472 (22:17091610 G>A), RS1001098260 (22:17086059 T>A), RS1001121095 (22:17107230 T>C), RS1001577926 (22:17096606 C>G,T), RS1001991986 (22:17115677 A>G), RS1002099232 (22:17085008 C>A), RS1002123571 (22:17106205 A>G), RS1002137278 (22:17101619 T>A)

Disease associations

OMIM: gene MIM:605461 | disease phenotypes: MIM:613953, MIM:177900, MIM:114580

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 51	Strong	Autosomal recessive
chronic mucocutaneous candidiasis	Supportive	Autosomal dominant

Mondo (3): immunodeficiency 51 (MONDO:0013500), psoriasis (MONDO:0005083), chronic mucocutaneous candidiasis (MONDO:0015279)

Orphanet (1): Chronic mucocutaneous candidiasis (Orphanet:1334)

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000142	Abnormal vagina morphology
HP:0000153	Abnormality of the mouth
HP:0000159	Abnormal lip morphology
HP:0000403	Recurrent otitis media
HP:0000478	Abnormality of the eye
HP:0000504	Abnormality of vision
HP:0000682	Abnormal dental enamel morphology
HP:0000790	Hematuria
HP:0000951	Abnormality of the skin
HP:0000962	Hyperkeratosis
HP:0000964	Eczematoid dermatitis
HP:0000988	Skin rash
HP:0000989	Pruritus
HP:0001231	Abnormal fingernail morphology
HP:0001250	Seizure
HP:0001581	Recurrent skin infections
HP:0001597	Abnormal nail morphology
HP:0001821	Broad nail
HP:0002090	Pneumonia
HP:0002105	Hemoptysis
HP:0002205	Recurrent respiratory infections
HP:0002715	Abnormality of the immune system
HP:0002719	Recurrent infections
HP:0002726	Recurrent Staphylococcus aureus infections
HP:0002728	Chronic mucocutaneous candidiasis
HP:0002837	Recurrent bronchitis
HP:0004306	Abnormal endocardium morphology
HP:0004332	Abnormal lymphocyte morphology

GWAS associations

35 associations (top):

Study	Trait	p-value
GCST002579_27	Heschl’s gyrus morphology	2.000000e-06
GCST004608_118	Granulocyte percentage of myeloid white cells	3.000000e-78
GCST004609_165	Monocyte percentage of white cells	8.000000e-14
GCST004609_166	Monocyte percentage of white cells	6.000000e-114
GCST004610_100	White blood cell count	5.000000e-12
GCST004625_190	Monocyte count	1.000000e-24
GCST004625_191	Monocyte count	4.000000e-136
GCST004625_192	Monocyte count	7.000000e-12
GCST004626_163	Myeloid white cell count	4.000000e-13
GCST006585_411	Blood protein levels	0.000000e+00
GCST008471_14	Non-alcoholic fatty liver disease activity score in non-alcoholic fatty liver disease	4.000000e-08
GCST90002381_275	Eosinophil count	2.000000e-13
GCST90002381_276	Eosinophil count	3.000000e-25
GCST90002381_437	Eosinophil count	3.000000e-12
GCST90002381_438	Eosinophil count	4.000000e-11
GCST90002382_549	Eosinophil percentage of white cells	7.000000e-11
GCST90002389_432	Lymphocyte percentage of white cells	2.000000e-12
GCST90002393_474	Monocyte count	3.000000e-13
GCST90002393_475	Monocyte count	1.000000e-68
GCST90002393_476	Monocyte count	0.000000e+00
GCST90002393_477	Monocyte count	7.000000e-25
GCST90002393_478	Monocyte count	9.000000e-105
GCST90002393_479	Monocyte count	2.000000e-09
GCST90002394_202	Monocyte percentage of white cells	3.000000e-33
GCST90002394_203	Monocyte percentage of white cells	0.000000e+00
GCST90002394_204	Monocyte percentage of white cells	8.000000e-14
GCST90002394_205	Monocyte percentage of white cells	2.000000e-53
GCST90002398_68	Neutrophil count	4.000000e-17
GCST90002398_69	Neutrophil count	5.000000e-11
GCST90002398_70	Neutrophil count	3.000000e-10

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0008421	non-alcoholic fatty liver disease severity measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004833	neutrophil count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002178	Candidiasis, Chronic Mucocutaneous	C01.150.703.160.088; C01.150.703.302.100; C01.800.200.100; C17.800.838.208.165; C23.550.291.500.250
D011565	Psoriasis	C17.800.859.675

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3580485 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4819554	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Psoriasis

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4819554	IL17RA	3	2.50	1	Tumor necrosis factor alpha (TNF-alpha) inhibitors
rs879577	IL17RA		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — IL-17 receptor family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
brodalumab	Binding	9.16	pKd

Binding affinities (BindingDB)

287 measured of 292 human assays (292 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-cyano-N-((1S)-1- cyclohexyl-2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrrole-2-carboxamide	IC50	5.5 nM	US-20250154138: Small Molecule IL-17A Modulators
N-(1-(4- ethylcyclohexyl)-2-((2- (methylcarbamoyl)-2- (7-oxo-6,8- diazaspiro[3.5]nonan-6- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	5.6 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (7-oxo-6,8- diazaspiro[3.5]nonan-6- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	5.8 nM	US-20250154138: Small Molecule IL-17A Modulators
N-(1-(6-chloro-1,2,3,4- tetrahydronaphthalen-2- yl)-2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	6.3 nM	US-20250154138: Small Molecule IL-17A Modulators
N-(1-(5-chloro-1,2,3,4- tetrahydronaphthalen-2- yl)-2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	6.5 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-((1r,4S)-4- ethylcyclohexyl)-2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	7 nM	US-20250154138: Small Molecule IL-17A Modulators
N-(1-(4- ethylcyclohexyl)-2-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	7.5 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	9.5 nM	US-20250154138: Small Molecule IL-17A Modulators
N-(1-(4- isopropylcyclohexyl)-2- ((2-(methylcarbamoyl)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	10 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-(((R)-1- cyclohexyl-2- hydroxyethyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	10 nM	US-20250154138: Small Molecule IL-17A Modulators
N-(1-(4- ethylcyclohexyl)-2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	10 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl-2- ((2-(5-methyl-2-oxo-5- (trifluoromethyl) tetrahydropyrimidin- 1(2H)-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	10.9 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cycloheptyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide	IC50	11 nM	US-20250154138: Small Molecule IL-17A Modulators
N-(2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1-(3- methylcyclohexyl)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	12 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-(5-ethyl-5-methyl- 2- oxotetrahydropyrimidin- 1(2H)-yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide	IC50	15 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (7-oxo-6,8- diazaspiro[3.5]nonan-6- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide	IC50	15 nM	US-20250154138: Small Molecule IL-17A Modulators
5-((S)-2-cyclohexyl-2- (1-methyl-1H-pyrazole- 5- carboxamido)acetamido)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- indene-2-carboxylic acid	IC50	15.3 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-(4,4- difluorocyclohexyl)-2- oxo-2-((2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2-((pyridazin-3- ylmethyl)carbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)ethyl)-4- methyl-1,2,5- oxadiazole-3- carboxamide	IC50	15.9 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-(((S)-1- cyclohexyl-2- hydroxyethyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	16 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1- cyclopropyl-1H- pyrazole-5-carboxamide	IC50	16 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((2S)-1,1- dicyclopropyl-3-((2- ((dicyclopropylmethyl) carbamoyl)-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide	IC50	16.5 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((2S)-1,1- dicyclopropyl-3-((2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2-((tetrahydrofuran-3- yl)carbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-3-oxopropan- 2-yl)-4-methyl-1,2,5- oxadiazole-3- carboxamide	IC50	17.3 nM	US-20250154138: Small Molecule IL-17A Modulators
N-(2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1-(4- methylcyclohexyl)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	18 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((S)-1,1- dicyclopropyl-3-((2- (cyclopropyl((S)-2-oxo- 4- (trifluoromethyl) imidazolidin- 1-yl)-13-methyl)- 2,3-dihydro-213- benzofuran-6- yl)amino)-3-oxopropan- 2-yl)-1-isopropyl-1H- pyrazole-5-carboxamide	IC50	18.6 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2-((pyridin-2- ylmethyl)carbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	19 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((2S)-1,1- dicyclopropyl-3-((2- (methylcarbamoyl)-2- (7-oxo-6,8- diazaspiro[3.5]nonan-6- yl)-2,3-dihydro-1H- inden-5-yl)amino)-3- oxopropan-2-yl)-1- methyl-1H-pyrazole-5- carboxamide	IC50	19 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2- (isobutylcarbamoyl)-2- ((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	19 nM	US-20250154138: Small Molecule IL-17A Modulators
4-cyano-N-((1S)-1- cyclohexyl-2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrrole-2-carboxamide	IC50	19 nM	US-20250154138: Small Molecule IL-17A Modulators
N-(1-(7-chloro-1,2,3,4- tetrahydronaphthalen-2- yl)-2-((2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	19.8 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2-((4- methoxybenzyl)carbam oyl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	20 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-((R)-4-(4- methoxybenzyl)-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	20 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-(4,4- difluorocyclohexyl)-2- ((2-(2-hydroxypropan- 2-yl)-2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-4-methyl- 1,2,5-oxadiazole-3- carboxamide	IC50	20.9 nM	US-20250154138: Small Molecule IL-17A Modulators
5-((S)-2-cyclohexyl-2- (3- methylbenzamido) acetamido)- 2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- N-methyl-2,3-dihydro- 1H-indene-2- carboxamide	IC50	21 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-2-((2- carbamoyl-2-((R)-4- isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1- cycloheptyl-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	22 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-2-((2-((1- cyclobutyl-2- hydroxyethyl) carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-1- cyclohexyl-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide	IC50	22 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-((2- fluorobenzyl)carbamoyl)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	22.4 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (8-oxo-7,9- diazaspiro[4.5]decan-7- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	22.4 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide	IC50	22.6 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((2S)-1,1- dicyclopropyl-3-((2-((3- fluorophenyl)carbamoyl)- 2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide	IC50	23.3 nM	US-20250154138: Small Molecule IL-17A Modulators
5-((S)-2-benzamido-2- cyclohexylacetamido)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- N-methyl-2,3-dihydro- 1H-indene-2- carboxamide	IC50	24 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-((R)-4-(4- methylbenzyl)-2- oxoimidazolidin-1-yl)- 2-(methylcarbamoyl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	24 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((2S)-1,1- dicyclopropyl-3-((2-((2- ethylphenyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-3- oxopropan-2-yl)-4- methyl-1,2,5- oxadiazole-3- carboxamide	IC50	24.5 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 4-methyl-1,2,5- oxadiazole-3- carboxamide	IC50	25 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-((1-cyclopentyl-2- hydroxyethyl)carbamoyl)- 2-((R)-4-isopropyl-2- oxoimidazolidin-1-yl)- 2,3-dihydro-1H-inden- 5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	25 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-(5,5-dimethyl-2- oxotetrahydropyrimidin- 1(2H)-yl)-2- (methylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide	IC50	26 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-2-((2- (bicyclo[1.1.1]pentan-1- ylcarbamoyl)-2-(6-oxo- 5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-1- cyclohexyl-2-oxoethyl)- 1-methyl-1H-pyrazole- 5-carboxamide	IC50	26.9 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-oxo-2-((2-(((S)-2- oxo-4- (trifluoromethyl) imidazolidin-1-yl) methyl)-2,3- dihydrobenzofuran-6- yl)amino)ethyl)-1- methyl-1H-pyrazole-5- carboxamide	IC50	27.1 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2- (methylcarbamoyl)-2- (6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-ethyl-1H- pyrazole-5-carboxamide	IC50	28 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-(4,4- difluorocyclohexyl)-2- oxo-2-((2-(6-oxo-5,7- diazaspiro[2.5]octan-5- yl)-2-(m- tolylcarbamoyl)-2,3- dihydro-1H-inden-5- yl)amino)ethyl)-4- methyl-1,2,5- oxadiazole-3- carboxamide	IC50	28.6 nM	US-20250154138: Small Molecule IL-17A Modulators
N-((1S)-1-cyclohexyl- 2-((2-((R)-4-isopropyl- 2-oxoimidazolidin-1- yl)-2-((2,2,2- trifluoroethyl)carbamoyl)- 2,3-dihydro-1H- inden-5-yl)amino)-2- oxoethyl)-1-methyl-1H- pyrazole-5-carboxamide	IC50	30 nM	US-20250154138: Small Molecule IL-17A Modulators

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	4
Nickel	decreases expression, increases expression	3
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
sodium arsenite	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
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, affects expression	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Catechin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Environmental Pollutants	affects expression	1
Ozone	affects expression, increases abundance	1
Phthalic Acids	decreases methylation	1
Smoke	decreases expression	1
Thimerosal	decreases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	decreases expression	1
Acrylamide	increases expression	1

Cellosaurus cell lines

6 cell lines: 3 transformed cell line, 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A8CK	HEK-Blue IL-17C	Transformed cell line	Female
CVCL_D1WV	Abcam A-549 IL17RA KO	Cancer cell line	Male
CVCL_E4JD	Genomeditech HEK-293 H_IL17A Reporter	Transformed cell line	Female
CVCL_SS44	HAP1 IL17RA (-) 1	Cancer cell line	Male
CVCL_UF32	HEK-Blue IL-17	Transformed cell line	Female
CVCL_XP77	HAP1 IL17RA (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00096980	PHASE4	COMPLETED	A Study to Evaluate Raptiva in Combination With Topical Psoriasis Therapies
NCT00110981	PHASE4	COMPLETED	Utilization of Narrow Band Ultraviolet B (UVB) Light Therapy and Etanercept for the Treatment of Psoriasis
NCT00111124	PHASE4	COMPLETED	Enbrel® in Psoriatic Arthritis
NCT00150930	PHASE4	UNKNOWN	Home UVB Phototherapy for Psoriasis: Effectiveness, Quality of Life and Cost-Effectiveness
NCT00161655	PHASE4	COMPLETED	Study Evaluating Etanercept and Methotrexate in Plaque Psoriasis
NCT00195507	PHASE4	COMPLETED	Study Evaluating Etanercept in the Treatment of Subjects With Psoriasis
NCT00249808	PHASE4	COMPLETED	A Study of Efalizumab in Participants With Moderate to Severe Chronic Psoriasis Who Have Failed, Have a Contraindication to, or Are Intolerant of Other Systemic Therapies
NCT00287118	PHASE4	COMPLETED	A Multicentre, Open Label Phase IIIb/IV Study of Subcutaneously Administered Raptiva in the Treatment of Adult Subjects With Moderate to Severe Plaque Psoriasis
NCT00312026	PHASE4	COMPLETED	A Study to Evaluate the Safety and Efficacy of Efalizumab in Adult Patients With Plaque Psoriasis Involving the Hands and/or Feet
NCT00332332	PHASE4	COMPLETED	Canadian Assessment of Patient Outcomes and Effectiveness of Etanercept (Enbrel) in Psoriasis
NCT00336973	PHASE4	COMPLETED	A Study to Evaluate Raptiva in Subjects With Chronic Moderate or Worse Plaque Psoriasis Who Have Had an Inadequate Response to an Anti-TNF Agent
NCT00436540	PHASE4	COMPLETED	A Comparison Between Clobetasol Propionate 0.05% (Clobex®) Spray and Clobetasol Propionate 0.05% (Olux®) Foam
NCT00437619	PHASE4	COMPLETED	A Study of Sequential Treatment With Daivobet (Betamethasone Dipropionate Plus Calcipotriol) and Daivonex (Calcipotriol) in Patients With Psoriasis.
NCT00462072	PHASE4	COMPLETED	Centocor Microarray Study of Patients
NCT00581165	PHASE4	COMPLETED	Study Evaluating Safety of Etanercept in Treatment of Patients With Moderate to Severe Psoriasiswith Etanercept
NCT00581555	PHASE4	COMPLETED	Evaluation of Etanercept in Patients With Plaque Psoriasis After Stopping Ciclosporin Therapy
NCT00655564	PHASE4	COMPLETED	Long-Term One Year Use of Alefacept (Amevive®) in Moderate to Severe Chronic Plaque Type Psoriasis
NCT00663052	PHASE4	COMPLETED	Study Evaluating Etanercept for the Treatment of Moderate to Severe Psoriasis
NCT00669123	PHASE4	COMPLETED	Chondroitin Sulphate Efficay/Safety in Patients With Knee Osteoarthritis and Psoriasis
NCT00669214	PHASE4	COMPLETED	A Study to Evaluate the Safety and Efficacy of Efalizumab in Adult Patients With Moderate to Severe Plaque Psoriasis With Involvement of the Scalp
NCT00686595	PHASE4	COMPLETED	A Study to Evaluate the Switch From Etanercept to Infliximab in Subjects With Moderate-to-Severe Psoriasis (Study P05133)
NCT00697034	PHASE4	TERMINATED	Effects of Capsaicin on the Structure, Distribution, and Function of Cutaneous Small Nerve Fibers in Psoriatic Skin
NCT00723437	PHASE4	COMPLETED	Evaluation of the Efficacy of Acitretin Therapy for Nail Psoriasis
NCT00735787	PHASE4	COMPLETED	Controlled Study of Humira in Subjects With Chronic Plaque Psoriasis of the Hands and/or Feet
NCT00748020	PHASE4	COMPLETED	Narrow-Band UVB-Therapy in Psoriasis
NCT00763529	PHASE4	COMPLETED	Elocon vs Fluticasone in Localized Psoriasis (P03197)
NCT00791765	PHASE4	COMPLETED	Moderate to Severe Plaque Psoriasis With Scalp Involvement
NCT00842153	PHASE4	COMPLETED	Evaluation of the Efficacy and Tolerability of Clobetasol Propionate Foam Compared to Vehicle Foam
NCT00932113	PHASE4	COMPLETED	Mechanism of Action Study for Psoriasis
NCT00940862	PHASE4	COMPLETED	Effect of Adalimumab on Vascular Inflammation in Patients With Moderate to Severe Plaque Psoriasis
NCT00967538	PHASE4	COMPLETED	Safety and Efficacy of Etanercept in Patients With Psoriasis Who Failed to Respond to Other Biologic Treatments
NCT00992394	PHASE4	COMPLETED	Study Comparing 2 Different Strategies For Management of Subjects With Plaque Psoriasis Who Have Responded to Etanercept
NCT01039142	PHASE4	COMPLETED	Dose Ranging Study to Assess the Efficacy and Safety of Acitretin in Severe Plaque Type Psoriasis
NCT01053819	PHASE4	COMPLETED	Can We Miss Pigmented Lesions in Psoriasis Patients?
NCT01059773	PHASE4	COMPLETED	A Safety and Efficacy Study of Ustekinumab in Patients With Plaque Psoriasis Who Have Had an Inadequate Response to Methotrexate
NCT01077882	PHASE4	COMPLETED	Analysis of the Quality of Life, the Clinical Effectiveness and Cost-effectiveness of a Novel Educational Programme in Patients With Psoriasis and Atopic Dermatitis
NCT01079988	PHASE4	COMPLETED	Study of Therapeutic Options for Subjects Discontinuing Efalizumab and Experiencing Disease Recurrence
NCT01088165	PHASE4	UNKNOWN	The Influence of Adalimumab on Cardiovascular and Metabolic Risk in Psoriasis
NCT01132235	PHASE4	UNKNOWN	An Open-label Study to Evaluate the Efficacy of Re-treatment for Patients With a History of Etanercept Use
NCT01137032	PHASE4	COMPLETED	Study to Evaluate Effect of Pandel Cream 0.1% on HPA Axis in Pediatric and Adult Population