IL17RC

protein-coding

interleukin 17 receptor C, the group of Interleukin receptors

Gene summary

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. [provided by RefSeq, Feb 2011]

MANE transcript

NM_153460.4

Inheritance

AR, AD

ClinVar variants

P:9U:427B:243

Top phenotype

Candiasis, familial, 9

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr3:9,917,074-9,933,630

External References & Databases

Ensembl (ENSG00000163702)

Transcript & Mutation Effects

hg38 • Region Span ~16.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

candidiasis, familial, 9LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0014642

Submitter: Labcorp Genetics (formerly Invitae)

candidiasis, familial, 9STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014642

Submitter: PanelApp Australia

chronic mucocutaneous candidiasisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015279

Submitter: Orphanet

Clinical Genomic Database (CGD)

Candiasis, familial, 9AR

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: Individuals have been described as susceptible to Candida albicansinfections, and awareness may allow early detection and early treatment of infections

Refs: 25918342

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IL17RC variants in ClinVar

4 Conditions Cataloged

Candidiasis, familial, 9Total: 821

not specifiedTotal: 184

not providedTotal: 52

IL17RC-related disorderTotal: 14

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153460.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			9 clinvar	203 clinvar	7 clinvar	219
missense			376 clinvar	28 clinvar	4 clinvar	408
nonsense	1 clinvar	4 clinvar	14 clinvar			19
start loss						0
frameshift		2 clinvar	12 clinvar			14
splice donor/acceptor (+/-2bp)		2 clinvar	16 clinvar	1 clinvar		19
Total	1	8	427	232	11	679

Highest pathogenic variant AF is 0.0003079194

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 341 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153460.4	RefSeq	NP_703190.2	19	MANE Select
ENST00000403601.8	Ensembl	ENSP00000384969.3	19	MANE Select
NM_001203263.2	RefSeq	NP_001190192.2	18	Standard
NM_001203264.2	RefSeq	NP_001190193.2	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

IL-17 signaling pathway - Homo sapiens (human)
Cytokine-cytokine receptor interaction - Homo sapiens (human)
IL17 signaling pathway

Biological Process

defense response to fungus
granulocyte chemotaxis
interleukin-17-mediated signaling pathway
positive regulation of cytokine production involved in inflammatory response
positive regulation of interleukin-6 secretion

Molecular Function

signaling receptor binding
interleukin-17 receptor activity

Cellular Component

plasma membrane
cell surface
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000295981
Coding exons: 19
Length: 16557
Individuals with no LoFs: 124302
Homozygous LoFs: 10
Heterozygous LoFs: 1436
Defined: 125748
p: 0.00577

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0924	441	447	0.988	0.0000237	4973
Missense (PolyPhen)		81	91.844	0.88193		1166
Synonymous	-1.26	224	201	1.11	0.0000117	1679
Loss of Function	2.28	29	45.6	0.636	0.00000241	447

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0026	0.0023	notable
Latino/Admixed American	0.0049	0.0039	notable
Ashkenazi Jewish	0.0016	0.00099	notable
East Asian	0.00044	0.00044	rare
Finnish	0.0057	0.0050	notable
European (Non-Finnish)	0.011	0.0093	notable
South Asian	0.0020	0.0015	notable
Other	0.011	0.0083	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RA (PubMed:16785495). Receptor for the heterodimer formed by IL17A and IL17B as part of a heterodimeric complex with IL17RA (PubMed:18684971). Has also been shown to be the cognate receptor for IL17F and to bind IL17A with high affinity without the need for IL17RA (PubMed:17911633). Activation of IL17RC leads to induction of expression of inflammatory chemokines and cytokines such as CXCL1 (PubMed:16785495). {ECO:0000269|PubMed:16785495, ECO:0000269|PubMed:17911633, ECO:0000269|PubMed:18684971}.; FUNCTION: Isoform 6: Does not bind IL17A or IL17F. {ECO:0000269|PubMed:16785495}.; FUNCTION: Isoform 8: Receptor for both IL17A and IL17F. {ECO:0000269|PubMed:16785495}.;
Disease: DISEASE: 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. {ECO:0000269|PubMed:25918342}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.931
RVIS EVS: 2.09
RVIS percentile EVS: 97.87

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.252

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium