IL17RC

Summary

IL17RC (interleukin 17 receptor C, HGNC:18358) is a protein-coding gene on chromosome 3p25.3, encoding Interleukin-17 receptor C (Q8NAC3). Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity.

This gene encodes a single-pass type I membrane protein that shares similarity with the interleukin-17 receptor (IL-17RA). Unlike IL-17RA, which is predominantly expressed in hemopoietic cells, and binds with high affinity to only IL-17A, this protein is expressed in nonhemopoietic tissues, and binds both IL-17A and IL-17F with similar affinities. The proinflammatory cytokines, IL-17A and IL-17F, have been implicated in the progression of inflammatory and autoimmune diseases. Multiple alternatively spliced transcript variants encoding different isoforms have been detected for this gene, and it has been proposed that soluble, secreted proteins lacking transmembrane and intracellular domains may function as extracellular antagonists to cytokine signaling.

Source: NCBI Gene 84818 — RefSeq curated summary.

At a glance

• Gene–disease (curated): candidiasis, familial, 9 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 901 total — 1 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 38
• MANE Select transcript: NM_153460

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18358
Approved symbol	IL17RC
Name	interleukin 17 receptor C
Location	3p25.3
Locus type	gene with protein product
Status	Approved
Aliases	IL17-RL
Ensembl gene	ENSG00000163702
Ensembl biotype	protein_coding
OMIM	610925
Entrez	84818

Gene structure

Transcript identifiers

Ensembl transcripts: 143 — 116 protein_coding, 15 nonsense_mediated_decay, 12 retained_intron

ENST00000295981, ENST00000383812, ENST00000403601, ENST00000412901, ENST00000413608, ENST00000416074, ENST00000424206, ENST00000434756, ENST00000436503, ENST00000438091, ENST00000440502, ENST00000451165, ENST00000451231, ENST00000451271, ENST00000455057, ENST00000464406, ENST00000465794, ENST00000466046, ENST00000466712, ENST00000469686, ENST00000476810, ENST00000478206, ENST00000483582, ENST00000490512, ENST00000494365, ENST00000497387, ENST00000498214, ENST00000696815, ENST00000696816, ENST00000696817, ENST00000696818, ENST00000696819, ENST00000696820, ENST00000696821, ENST00000696822, ENST00000696823, ENST00000696824, ENST00000696825, ENST00000696826, ENST00000696827, ENST00000696828, ENST00000696829, ENST00000696830, ENST00000696831, ENST00000696832, ENST00000696833, ENST00000696834, ENST00000869944, ENST00000869945, ENST00000869946, ENST00000869947, ENST00000869948, ENST00000869949, ENST00000869950, ENST00000869951, ENST00000869952, ENST00000869953, ENST00000869954, ENST00000869955, ENST00000869956, ENST00000869957, ENST00000869958, ENST00000869959, ENST00000869960, ENST00000869961, ENST00000869962, ENST00000869963, ENST00000869964, ENST00000869965, ENST00000869966, ENST00000869967, ENST00000869968, ENST00000869969, ENST00000869970, ENST00000869971, ENST00000869972, ENST00000869973, ENST00000869974, ENST00000869975, ENST00000869976, ENST00000869977, ENST00000869978, ENST00000869979, ENST00000869980, ENST00000869981, ENST00000869982, ENST00000869983, ENST00000869984, ENST00000869985, ENST00000869986, ENST00000869987, ENST00000869988, ENST00000869989, ENST00000869990, ENST00000869991, ENST00000869992, ENST00000869993, ENST00000869994, ENST00000869995, ENST00000869996, ENST00000869997, ENST00000869998, ENST00000869999, ENST00000870000, ENST00000870001, ENST00000870002, ENST00000870003, ENST00000870004, ENST00000870005, ENST00000870006, ENST00000870007, ENST00000870008, ENST00000870009, ENST00000870010, ENST00000870011, ENST00000870012, ENST00000870013, ENST00000870014, ENST00000870015, ENST00000870016, ENST00000870017, ENST00000870018, ENST00000870019, ENST00000870020, ENST00000870021, ENST00000870022, ENST00000870023, ENST00000870024, ENST00000870025, ENST00000870026, ENST00000870027, ENST00000870028, ENST00000930661, ENST00000930662, ENST00000930663, ENST00000972532, ENST00000972533, ENST00000972534, ENST00000972535, ENST00000972536, ENST00000972537, ENST00000972538, ENST00000972539

RefSeq mRNA: 10 — MANE Select: NM_153460 NM_001203263, NM_001203264, NM_001203265, NM_001367278, NM_001367279, NM_001367280, NM_001410711, NM_032732, NM_153460, NM_153461

CCDS: CCDS2590, CCDS2591, CCDS46746, CCDS56240, CCDS56241, CCDS74898, CCDS93201, CCDS93202, CCDS93203

Canonical transcript exons

ENST00000403601 — 19 exons

Exon	Start	End
ENSE00001939483	9932953	9933621
ENSE00003478587	9928166	9928220
ENSE00003495269	9917098	9917420
ENSE00003498725	9928305	9928486
ENSE00003506466	9920925	9920969
ENSE00003539240	9924232	9924291
ENSE00003587578	9917713	9917734
ENSE00003594299	9930895	9930943
ENSE00003597527	9930400	9930459
ENSE00003600280	9930028	9930149
ENSE00003640970	9918335	9918409
ENSE00003644258	9932608	9932703
ENSE00003662620	9929852	9929897
ENSE00003674336	9932820	9932858
ENSE00003678196	9923881	9924020
ENSE00003679199	9920491	9920602
ENSE00003693049	9918500	9918609
ENSE00003740417	9917923	9918075
ENSE00003917403	9928580	9928630

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 97.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.0779 / max 314.0853, expressed in 1668 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35256	14.1654	1665
35257	0.6755	319
35258	0.2370	88

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	97.12	gold quality
right lobe of liver	UBERON:0001114	96.28	gold quality
right adrenal gland cortex	UBERON:0035827	96.28	gold quality
right adrenal gland	UBERON:0001233	96.08	gold quality
mucosa of stomach	UBERON:0001199	95.99	gold quality
left adrenal gland cortex	UBERON:0035825	95.83	gold quality
skin of abdomen	UBERON:0001416	95.76	gold quality
pituitary gland	UBERON:0000007	95.51	gold quality
skin of leg	UBERON:0001511	95.50	gold quality
left adrenal gland	UBERON:0001234	95.24	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.17	gold quality
apex of heart	UBERON:0002098	94.84	gold quality
adrenal cortex	UBERON:0001235	94.70	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.25	gold quality
right lobe of thyroid gland	UBERON:0001119	94.17	gold quality
lower esophagus	UBERON:0013473	94.17	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.16	gold quality
minor salivary gland	UBERON:0001830	93.99	gold quality
left uterine tube	UBERON:0001303	93.91	gold quality
lower esophagus mucosa	UBERON:0035834	93.73	gold quality
left lobe of thyroid gland	UBERON:0001120	93.52	gold quality
adrenal gland	UBERON:0002369	93.31	gold quality
saliva-secreting gland	UBERON:0001044	93.00	gold quality
esophagus	UBERON:0001043	92.91	gold quality
ectocervix	UBERON:0012249	92.91	gold quality
right ovary	UBERON:0002118	92.87	gold quality
body of uterus	UBERON:0009853	92.74	gold quality
left ovary	UBERON:0002119	92.71	gold quality
right atrium auricular region	UBERON:0006631	92.71	gold quality
zone of skin	UBERON:0000014	92.55	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.42
E-MTAB-6142	no	90.62
E-CURD-112	no	2.53

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 23)

• IL-17RL exists as multiple isoforms due to extensive alternative splicing. Changes in RNA IL-17RL splicing occur in advanced cancers. (PMID:16688746)
• The biologic activity of IL-17 is dependent on a complex composed of receptors IL-17RA and IL-17RC. (PMID:16785495)
• IL-17RC functions as a receptor for both IL-17A and IL-17F; a soluble version of this protein should be an effective antagonist of IL-17A and IL-17F mediated inflammatory diseases. (PMID:17911633)
• 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)
• Interleukin-17F is inhibited by the IL-17RC receptor, a combination of soluble IL-17RA/IL-17RC receptors is required for inhibition of the IL-17F/IL-17A activity. (PMID:18684971)
• IL-17 and its receptor IL-17RC are involved in rheumatoid arthritis synovial fluid-mediated chemotaxis in human lung microvascular endothelial cell culture. (PMID:20173024)
• Overall, our study found a significant association of IL-17RC gene polymorphisms with AIS in a Chinese Han population, indicating IL-17RC gene may be as a susceptibility gene for AIS. (PMID:22744455)
• 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)
• IL-17RC predisposes to the development of adolescent idiopathic scoliosis in a Chinese Han population. (PMID:22999050)
• results suggested a potential involvement of IL-17RC+CD8+ T cells in pathogenesis of ocular sarcoidosis (PMID:24885153)
• human IL-17RC is essential for mucocutaneous immunity to C. albicans but is otherwise largely redundant. (PMID:25918342)
• methylation of IL17RC could play as a marker in CNV and degeneration of RPE cells in vitro. (PMID:26731132)
• Interleukin 17A (IL17a) and interleukin-23 (IL-23) - dependent interleukin-17 receptor C (IL-17RC) are expressed by sputum and neutrophils in deltaF508-CFTR protein (F508del) cystic fibrosis patients. (PMID:27155366)
• IL-17RC rs708567 polymorphism in A/A genotype, G/G genotype, and G/a genotype did not seem to influence RA susceptibility in Tunisian population. (PMID:29584788)
• Genetic Variants on IL-17 are associated with development of atherosclerotic diseases. (PMID:29695654)
• Five SNPs in the IL17RC (and COL6A1) genes were found to be associated with susceptibility to ossification of the posterior longitudinal ligament in Han Chinese patients. (PMID:29764467)
• Genetic study revealed no association between IL-17RC, and SNPs and acute kidney transplant graft rejection. Nevertheless, a significant improvement of graft survival was found in kidney transplant recipients carrying the IL-17RC*G/G, and *G/A genotypes. (PMID:30024651)
• An increase in IL17RC gene expression levels in peripheral blood samples was found in ossification of the posterior longitudinal ligament patients. (PMID:31291973)
• Interleukin-17 receptor C gene polymorphism reduces treatment effect and promotes poor prognosis of ischemic stroke. (PMID:31481525)
• The crystal structure of the interleukin 17 receptor C (IL-17RC):interleukin 17F (IL-17F) complex provides a structural basis for IL-17F signaling through IL-17RC. (PMID:32187518)
• IL-17 Receptor C Signaling Controls CD4(+) TH17 Immune Responses and Tissue Injury in Immune-Mediated Kidney Diseases. (PMID:35167487)
• IL-17A promotes Helicobacter pylori-induced gastric carcinogenesis via interactions with IL-17RC. (PMID:36125689)
• Associations of IL-17 and IL-17 receptor polymorphisms with Behcet’s disease in Denizli Province of Turkey. (PMID:36701075)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	il17ra1a	ENSDARG00000058244
danio_rerio		ENSDARG00000070299
danio_rerio	il17ra2	ENSDARG00000100137
danio_rerio	il17ra1b	ENSDARG00000103208
mus_musculus	Il17rc	ENSMUSG00000030281
rattus_norvegicus	Il17rc	ENSRNOG00000027376
caenorhabditis_elegans		WBGENE00013415

Paralogs (4): IL17RB (ENSG00000056736), IL17RD (ENSG00000144730), IL17RE (ENSG00000163701), IL17RA (ENSG00000177663)

Protein

Protein identifiers

Interleukin-17 receptor C — Q8NAC3 (reviewed: Q8NAC3)

Alternative names: Interleukin-17 receptor homolog, Interleukin-17 receptor-like protein, ZcytoR14

All UniProt accessions (25): A0A8Q3SIU5, A0A8Q3SIV5, A0A8Q3SJ01, A0A8Q3SJ19, A0A8Q3SJ22, Q8NAC3, A0A8Q3SJ28, A0A8Q3SJ61, A0A8Q3SJJ9, A0A8Q3WLK3, A0A8Q3WLK4, A0A8Q3WLP4, A0A8Q3WM30, A8K3Q5, B4DI24, C9JSZ3, C9K0M1, F6X4Z5, F8WB43, F8WC09, F8WD65, F8WE27, F8WEG5, G3V177, Q8N2D7

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 and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity. Receptor for IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RA. Receptor for the heterodimer formed by IL17A and IL17B as part of a heterodimeric complex with IL17RA. Has also been shown to be the cognate receptor for IL17F and to bind IL17A with high affinity without the need for IL17RA. Upon binding of IL17F homodimer triggers downstream activation of TRAF6 and NF-kappa-B signaling pathway. Induces transcriptional activation of IL33, a potent cytokine that stimulates group 2 innate lymphoid cells and adaptive T-helper 2 cells involved in pulmonary allergic response to fungi. Promotes sympathetic innervation of peripheral organs by coordinating the communication between gamma-delta T cells and parenchymal cells. Stimulates sympathetic innervation of thermogenic adipose tissue by driving TGFB1 expression. Binding of IL17A-IL17F to IL17RA-IL17RC heterodimeric receptor complex triggers homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter through SEFIR domains. This leads to downstream 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. Primarily induces neutrophil activation and recruitment at infection and inflammatory sites. Stimulates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers. Receptor for both IL17A and IL17F. Does not bind IL17A or IL17F. Does not bind IL17A or IL17F. Receptor for both IL17A and IL17F.

Subunit / interactions. Homodimer; disulfide-linked. Heterodimer with IL17RA. Heterodimerization with IL17RA is independent of the cytoplasmic tail. Associates with non-glycosylated IL17RA constitutively. Binding of IL17A and IL17F induces association with glycosylated IL17RA. 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-IL17F forms complexes with IL17RA-IL17RC, but with lower affinity when compared to IL17A homodimer. IL17RC chain cannot distinguish between IL17A and IL17F molecules, potentially enabling the formation of topologically distinct complexes. Interacts (through SEFIR domain and extended downstream region) with TRAF3IP2/ACT1 (phosphorylated).

Subcellular location. Cell membrane.

Tissue specificity. Expressed in prostate, skeletal muscle, kidney and placenta (at protein level). Expressed in brain, cartilage, colon, heart, intestine, kidney, liver, lung, muscle, placenta, and prostate. Also detected in thyroid, trachea and adrenal gland. Low expression in thymus and leukocytes.

Disease relevance. Candidiasis, familial, 9 (CANDF9) [MIM:616445] A disorder characterized by 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.

Induction. By HGF and VEGF.

Isoforms (8)

UniProt ID	Names	Canonical?
Q8NAC3-1	1	yes
Q8NAC3-2	2
Q8NAC3-3	3
Q8NAC3-4	4
Q8NAC3-5	5, IL17RC
Q8NAC3-6	6, IL17RC-delta7,12
Q8NAC3-7	7, IL17RC-delta12
Q8NAC3-8	8, IL17RC-delta7

RefSeq proteins (10): NP_001190192, NP_001190193, NP_001190194, NP_001354207, NP_001354208, NP_001354209, NP_001397640, NP_116121, NP_703190, NP_703191 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013568	SEFIR_dom	Domain
IPR027841	IL-17_rcpt_C/E_N	Domain
IPR039465	IL-17_rcpt-like	Family

Pfam: PF08357, PF15037

UniProt features (77 total): strand 32, glycosylation site 9, helix 8, disulfide bond 7, splice variant 6, turn 4, topological domain 2, sequence conflict 2, signal peptide 1, chain 1, transmembrane region 1, sequence variant 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6HGA	X-RAY DIFFRACTION	2.6
7UWN	ELECTRON MICROSCOPY	3.01
6HG4	X-RAY DIFFRACTION	3.32
6HG9	X-RAY DIFFRACTION	3.62
7ZAN	X-RAY DIFFRACTION	5.06

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NAC3-F1	74.19	0.20

Antibody-complex structures (SAbDab): 1 — 6HGA

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 (7): 265–277, 341–391, 343–359, 400–409, 439–453, 481–488, 515–529

Glycosylation sites (9): 284, 297, 324, 334, 420, 443, 477, 189, 257

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: 204 (showing top): GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOCC_CELL_SURFACE, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_LEUKOCYTE_CHEMOTAXIS, GTGCCTT_MIR506, CTAGGAA_MIR384, GOBP_TAXIS, GOBP_LEUKOCYTE_MIGRATION, TGCTGAY_UNKNOWN, GOBP_PRODUCTION_OF_MOLECULAR_MEDIATOR_INVOLVED_IN_INFLAMMATORY_RESPONSE

GO Biological Process (7): inflammatory response (GO:0006954), positive regulation of interleukin-6 production (GO:0032755), interleukin-17A-mediated signaling pathway (GO:0038173), defense response to fungus (GO:0050832), granulocyte chemotaxis (GO:0071621), positive regulation of cytokine production involved in inflammatory response (GO:1900017), cytokine-mediated signaling pathway (GO:0019221)

GO Molecular Function (4): signaling receptor binding (GO:0005102), coreceptor activity (GO:0015026), interleukin-17 receptor activity (GO:0030368), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), cell surface (GO:0009986), 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
defense response	2
positive regulation of cytokine production	2
cellular anatomical structure	2
interleukin-6 production	1
regulation of interleukin-6 production	1
cytokine-mediated signaling pathway	1
response to fungus	1
leukocyte chemotaxis	1
granulocyte migration	1
cytokine production involved in inflammatory response	1
regulation of cytokine production involved in inflammatory response	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
protein binding	1
signaling receptor activity	1
cytokine receptor activity	1
interleukin-17 binding	1
binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

944 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL17RC	IL17F	Q96PD4	998
IL17RC	IL17A	Q16552	997
IL17RC	IL17RA	Q96F46	990
IL17RC	IL17RD	Q8NFM7	979
IL17RC	IL17RB	Q9NRM6	973
IL17RC	IL17C	Q9P0M4	951
IL17RC	IL17RE	Q8NFR9	951
IL17RC	IL25	Q9H293	908
IL17RC	IL17B	Q9UHF5	843
IL17RC	IL17D	Q8TAD2	818
IL17RC	TRAF3IP2	O43734	813
IL17RC	IL22	Q9GZX6	810
IL17RC	CXCL1	P09341	784
IL17RC	IL22RA1	Q8N6P7	766
IL17RC	TNFRSF1A	P19438	729

IntAct

2 interactions, top by confidence:

A	B	Type	Score
IL17RC	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (74): IL17RC (Affinity Capture-Western), ATP2A3 (Affinity Capture-MS), KCNT2 (Affinity Capture-MS), KCNJ11 (Affinity Capture-MS), GMCL1 (Affinity Capture-MS), DHRS3 (Affinity Capture-MS), ADCK2 (Affinity Capture-MS), PIGQ (Affinity Capture-MS), SLC12A4 (Affinity Capture-MS), LRP12 (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), ECEL1 (Affinity Capture-MS), ABCA3 (Affinity Capture-MS), ACVR2B (Affinity Capture-MS), MAP3K7 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LHF2, A0EQL2, D3YZF7, D7PDD4, O15533, O55237, O70394, O70540, O95866, P04278, P05111, P07994, P08689, P0C6B3, P0DP72, P15196, P17490, P18627, P40238, P55101, P60882, P97497, Q00657, Q08351, Q14393, Q14773, Q16671, Q3SWY4, Q5BK54, Q5NKT8, Q5TJE4, Q61790, Q61826, Q62588, Q6PZD2, Q6UVK1, Q6UWB1, Q7Z7M0, Q7Z7M1, Q86VR7

Diamond homologs: Q8K4C2, Q8NAC3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
IL17RC	“form complex”	“IL17R complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	6
Uncertain significance	494
Likely benign	324
Benign	36

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
372243	NM_153460.4(IL17RC):c.199C>T (p.Gln67Ter)	Pathogenic
1275790	NM_153460.4(IL17RC):c.989G>A (p.Trp330Ter)	Likely pathogenic
2501672	NM_153460.4(IL17RC):c.763-2_764del	Likely pathogenic
3393250	NM_153460.4(IL17RC):c.1059+2T>G	Likely pathogenic
372245	NM_153460.4(IL17RC):c.919C>T (p.Gln307Ter)	Likely pathogenic
3779765	NM_153460.4(IL17RC):c.1328del (p.Gln443fs)	Likely pathogenic
4845831	NM_153460.4(IL17RC):c.1201C>T (p.Arg401Ter)	Likely pathogenic

SpliceAI

2380 predictions. Top by Δscore:

Variant	Effect	Δscore
3:9917711:A:AG	acceptor_gain	1.0000
3:9917711:AG:A	acceptor_gain	1.0000
3:9917712:G:GG	acceptor_gain	1.0000
3:9917712:GG:G	acceptor_gain	1.0000
3:9917735:G:GG	donor_gain	1.0000
3:9918594:GTTTG:G	donor_gain	1.0000
3:9922489:T:TG	donor_gain	1.0000
3:9923876:A:AG	acceptor_gain	1.0000
3:9923877:CCAGC:C	acceptor_loss	1.0000
3:9923878:CAGC:C	acceptor_loss	1.0000
3:9923879:A:AG	acceptor_gain	1.0000
3:9923879:AG:A	acceptor_loss	1.0000
3:9923880:G:GT	acceptor_gain	1.0000
3:9923880:GC:G	acceptor_gain	1.0000
3:9923880:GCC:G	acceptor_gain	1.0000
3:9923880:GCCC:G	acceptor_gain	1.0000
3:9923880:GCCCT:G	acceptor_gain	1.0000
3:9928301:GCAG:G	acceptor_loss	1.0000
3:9928303:A:AG	acceptor_gain	1.0000
3:9928303:A:AT	acceptor_loss	1.0000
3:9928304:G:GT	acceptor_gain	1.0000
3:9928304:GA:G	acceptor_gain	1.0000
3:9928304:GAC:G	acceptor_gain	1.0000
3:9928304:GACC:G	acceptor_gain	1.0000
3:9928304:GACCC:G	acceptor_gain	1.0000
3:9928482:TGGAC:T	donor_gain	1.0000
3:9928483:GGAC:G	donor_gain	1.0000
3:9928483:GGACG:G	donor_gain	1.0000
3:9928484:GAC:G	donor_gain	1.0000
3:9928484:GACG:G	donor_gain	1.0000

AlphaMissense

4597 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:9933289:T:C	F691S	0.996
3:9933415:T:C	F733S	0.995
3:9928417:G:C	W401C	0.994
3:9928417:G:T	W401C	0.994
3:9933370:T:C	F718S	0.994
3:9933172:T:C	F652S	0.993
3:9933163:T:A	V649D	0.991
3:9930451:T:A	C515S	0.988
3:9930452:G:C	C515S	0.988
3:9930924:G:C	W527C	0.988
3:9930924:G:T	W527C	0.988
3:9933330:T:C	F705L	0.988
3:9933331:T:C	F705S	0.988
3:9933332:C:A	F705L	0.988
3:9933332:C:G	F705L	0.988
3:9928212:T:G	F361C	0.987
3:9928171:G:C	W347C	0.986
3:9928171:G:T	W347C	0.986
3:9932980:T:A	L588H	0.986
3:9933130:G:C	R638P	0.986
3:9933331:T:G	F705C	0.986
3:9930451:T:C	C515R	0.985
3:9933166:T:C	L650S	0.985
3:9933114:T:A	W633R	0.984
3:9933114:T:C	W633R	0.984
3:9933116:G:C	W633C	0.984
3:9933116:G:T	W633C	0.984
3:9928622:T:A	C439S	0.983
3:9928623:G:C	C439S	0.983
3:9933169:T:A	L651H	0.983

dbSNP variants (sampled 300 via entrez): RS1000063799 (3:9923325 G>A,T), RS1000128910 (3:9921449 C>T), RS1000365989 (3:9927080 C>T), RS1001014068 (3:9933772 T>A), RS1001054288 (3:9928390 G>A,C,T), RS1001071944 (3:9920018 T>A), RS1001301025 (3:9919096 G>A), RS1001505995 (3:9933023 C>G,T), RS1001537168 (3:9932776 G>A,C), RS1001640531 (3:9925416 G>A), RS1001872511 (3:9933851 C>G,T), RS1002182584 (3:9923747 T>G), RS1002531026 (3:9934047 C>T), RS1002701558 (3:9917042 G>A), RS1002749870 (3:9929553 G>A)

Disease associations

OMIM: gene MIM:610925 | disease phenotypes: MIM:616445

GenCC curated gene-disease

Disease	Classification	Inheritance
candidiasis, familial, 9	Strong	Autosomal recessive
chronic mucocutaneous candidiasis	Supportive	Autosomal dominant

Mondo (2): candidiasis, familial, 9 (MONDO:0014642), chronic mucocutaneous candidiasis (MONDO:0015279)

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

HPO phenotypes

38 total (30 of 38 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: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:0000988	Skin rash
HP:0000989	Pruritus
HP:0001231	Abnormal fingernail morphology
HP:0001250	Seizure
HP:0001597	Abnormal nail morphology
HP:0001821	Broad nail
HP:0002105	Hemoptysis
HP:0002205	Recurrent respiratory infections
HP:0002715	Abnormality of the immune system
HP:0002719	Recurrent infections
HP:0002728	Chronic mucocutaneous candidiasis
HP:0003593	Infantile onset
HP:0004306	Abnormal endocardium morphology
HP:0004370	Abnormality of temperature regulation
HP:0008388	Abnormal toenail morphology
HP:0008872	Feeding difficulties in infancy
HP:0010783	Erythema
HP:0011107	Recurrent aphthous stomatitis
HP:0011463	Childhood onset

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90000025_720	Appendicular lean mass	1.000000e-42

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs708567	IL17RC		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — IL-17 receptor family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Dexamethasone	increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
bufotalin	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	affects cotreatment, increases expression	1
terbufos	increases methylation	1
beta-lapachone	increases expression	1
sodium arsenite	increases abundance, increases expression	1
ochratoxin A	increases acetylation, increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	increases expression	1
Acrolein	decreases expression, increases abundance, affects cotreatment	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Gallic Acid	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Parathion	increases methylation	1
Sarin	increases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1
Cyclosporine	decreases expression	1
Cadmium Chloride	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E4JD	Genomeditech HEK-293 H_IL17A Reporter	Transformed cell line	Female
CVCL_UF32	HEK-Blue IL-17	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01386437	Not specified	RECRUITING	Natural History of Individuals With Immune System Problems That Lead to Fungal Infections
NCT03736252	Not specified	COMPLETED	Effectiveness of a Neoprene CMC Joint Orthosis
NCT05896410	Not specified	UNKNOWN	3D-Printed Hand Orthosis Versus Thermoplastic Orthosis