Candidiasis, familial, 9

Summary

Candidiasis, familial, 9 (MONDO:0014642) is a disease caused by IL17RC (GenCC Strong), with 4 cohort genes.

At a glance

• Causal gene: IL17RC (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 838

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	candidiasis, familial, 9
Mondo ID	MONDO:0014642
OMIM	616445
UMLS	C4225324
MedGen	906897
GARD	0016114
Is cancer (heuristic)	no

Also known as: CANDF9 · candidiasis, familial, 9 · candidiasis, familial, type 9 · chronic mucocutaneous candidiasis (disease) caused by mutation in IL17RC · IL17RC chronic mucocutaneous candidiasis (disease)

Data availability: 838 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › chronic mucocutaneous candidiasis › candidiasis, familial, 9

Related subtypes (11): candidiasis, familial, 1, chronic mucocutaneous candidiasis due to inhibition of lymphoblastic transformation, chronic mucocutaneous candidiasis due to intrinsic defect in lymphoblastic transformation, chronic mucocutaneous candidiasis due to lymphokine deficiency, chronic mucocutaneous candidiasis due to monocyte chemotactic disorder, candidiasis, familial, 3, candidiasis, familial, 4, immunodeficiency 51, candidiasis, familial, 6, autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome, candidiasis, familial, 8

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

325 uncertain significance, 246 likely benign, 14 benign, 9 conflicting classifications of pathogenicity, 4 likely pathogenic, 1 benign/likely benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
372243	NM_153460.4(IL17RC):c.199C>T (p.Gln67Ter)	IL17RC	Pathogenic	no assertion criteria provided
2501672	NM_153460.4(IL17RC):c.763-2_764del	IL17RC	Likely pathogenic	criteria provided, single submitter
3393250	NM_153460.4(IL17RC):c.1059+2T>G	IL17RC	Likely pathogenic	criteria provided, single submitter
372245	NM_153460.4(IL17RC):c.919C>T (p.Gln307Ter)	IL17RC	Likely pathogenic	criteria provided, single submitter
3779765	NM_153460.4(IL17RC):c.1328del (p.Gln443fs)	IL17RC	Likely pathogenic	criteria provided, single submitter
1004864	NM_153460.4(IL17RC):c.160G>A (p.Val54Met)	IL17RC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1060817	NM_153460.4(IL17RC):c.105+145C>T	IL17RC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1398542	NM_153460.4(IL17RC):c.170C>T (p.Pro57Leu)	IL17RC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1909238	NM_153460.4(IL17RC):c.1770C>G (p.Ser590Arg)	IL17RC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2084207	NM_153460.4(IL17RC):c.745C>T (p.Arg249Trp)	IL17RC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2201268	NM_153460.4(IL17RC):c.2057G>A (p.Arg686Gln)	IL17RC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2379690	NM_153460.4(IL17RC):c.185C>T (p.Ala62Val)	IL17RC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2383051	NM_153460.4(IL17RC):c.2155G>C (p.Gly719Arg)	IL17RC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2814302	NM_153460.4(IL17RC):c.88G>A (p.Ala30Thr)	IL17RC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2427431	NC_000003.11:g.(?9908818)(10085568_?)del	CIDEC	Uncertain significance	criteria provided, single submitter
1001477	NM_153460.4(IL17RC):c.2125G>C (p.Gly709Arg)	IL17RC	Uncertain significance	criteria provided, single submitter
1001948	NM_153460.4(IL17RC):c.1236G>A (p.Leu412=)	IL17RC	Uncertain significance	criteria provided, single submitter
1002278	NM_153460.4(IL17RC):c.1438dup (p.Ala480fs)	IL17RC	Uncertain significance	criteria provided, single submitter
1004349	NM_153460.4(IL17RC):c.2041G>A (p.Ala681Thr)	IL17RC	Uncertain significance	criteria provided, single submitter
1006079	NM_153460.4(IL17RC):c.1059C>T (p.Asp353=)	IL17RC	Uncertain significance	criteria provided, single submitter
1009796	NM_153460.4(IL17RC):c.629C>A (p.Pro210His)	IL17RC	Uncertain significance	criteria provided, single submitter
1011578	NM_153460.4(IL17RC):c.1487G>A (p.Trp496Ter)	IL17RC	Uncertain significance	criteria provided, single submitter
1017004	NM_153460.4(IL17RC):c.1717G>C (p.Glu573Gln)	IL17RC	Uncertain significance	criteria provided, multiple submitters, no conflicts
1021958	NM_153460.4(IL17RC):c.1088G>A (p.Gly363Asp)	IL17RC	Uncertain significance	criteria provided, single submitter
1022495	NM_153460.4(IL17RC):c.1622C>T (p.Pro541Leu)	IL17RC	Uncertain significance	criteria provided, single submitter
1024376	NM_153460.4(IL17RC):c.1772A>C (p.Glu591Ala)	IL17RC	Uncertain significance	criteria provided, single submitter
1025168	NM_153460.4(IL17RC):c.2147C>T (p.Ala716Val)	IL17RC	Uncertain significance	criteria provided, multiple submitters, no conflicts
1035290	NM_153460.4(IL17RC):c.106-131del	IL17RC	Uncertain significance	criteria provided, single submitter
1036347	NM_153460.4(IL17RC):c.341A>G (p.Glu114Gly)	IL17RC	Uncertain significance	criteria provided, single submitter
1036475	NM_153460.4(IL17RC):c.1546C>G (p.Leu516Val)	IL17RC	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
IL17RC	Strong	Autosomal recessive	candidiasis, familial, 9	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IL17RC	Orphanet:1334	Chronic mucocutaneous candidiasis
CRELD1	Orphanet:576235	Partial atrioventricular septal defect without ventricular hypoplasia
CRELD1	Orphanet:99067	Complete atrioventricular septal defect with ventricular hypoplasia
CRELD1	Orphanet:99068	Complete atrioventricular septal defect-tetralogy of Fallot
CIDEC	Orphanet:435651	CIDEC-related familial partial lipodystrophy

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
IL17RC	HGNC:18358	ENSG00000163702	Q8NAC3	Interleukin-17 receptor C	gencc,clinvar
CRELD1	HGNC:14630	ENSG00000163703	Q96HD1	Protein disulfide isomerase CRELD1	clinvar
IL17RE	HGNC:18439	ENSG00000163701	Q8NFR9	Interleukin-17 receptor E	clinvar
CIDEC	HGNC:24229	ENSG00000187288	Q96AQ7	Lipid transferase CIDEC	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IL17RC	Interleukin-17 receptor C	Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity.
CRELD1	Protein disulfide isomerase CRELD1	Protein disulfide isomerase.
IL17RE	Interleukin-17 receptor E	Specific functional receptor for IL17C.
CIDEC	Lipid transferase CIDEC	Lipid transferase specifically expressed in white adipose tissue, which promotes unilocular lipid droplet formation by mediating lipid droplet fusion.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 4 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	4	1.8×	0.097

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IL17RC	Other/Unknown	no		SEFIR_dom, IL-17_rcpt_C/E_N, IL-17_rcpt-like
CRELD1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
IL17RE	Other/Unknown	no		SEFIR_dom, IL-17_rcpt_C/E_N, IL-17_rcpt-like
CIDEC	Other/Unknown	no		CIDE-N_dom

Expression context

Cohort genes with no expression data: 0.

4 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adenohypophysis	1
right adrenal gland cortex	1
right lobe of liver	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
mucosa of transverse colon	1
skin of abdomen	1
skin of leg	1
adipose tissue	1
adipose tissue of abdominal region	1
subcutaneous adipose tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IL17RC	244	ubiquitous	marker	adenohypophysis, right lobe of liver, right adrenal gland cortex
CRELD1	134	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
IL17RE	156	ubiquitous	marker	skin of leg, skin of abdomen, mucosa of transverse colon
CIDEC	185	tissue_specific	marker	subcutaneous adipose tissue, adipose tissue, adipose tissue of abdominal region

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IL17RC	1,020
CRELD1	1,018
CIDEC	947
IL17RE	559

Intra-cohort edges

A	B	Sources
IL17RC	IL17RE	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IL17RC	Q8NAC3	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CRELD1	Q96HD1	81.68
CIDEC	Q96AQ7	74.19
IL17RE	Q8NFR9	68.77

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 4 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interleukin-17 signaling	2	169.2×	2e-04	IL17RC, IL17RE
Lipid particle organization	1	634.4×	0.004	CIDEC
Assembly of active LPL and LIPC lipase complexes	1	200.3×	0.008	CIDEC
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	29.7×	0.036	IL17RC
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	27.6×	0.036	CIDEC

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of triglyceride metabolic process	1	1053.2×	0.005	CIDEC
granulocyte chemotaxis	1	842.6×	0.005	IL17RC
lipid droplet fusion	1	842.6×	0.005	CIDEC
interleukin-17A-mediated signaling pathway	1	702.2×	0.005	IL17RC
cardiac septum development	1	421.3×	0.007	CRELD1
endocardial cushion development	1	351.1×	0.007	CRELD1
lipid droplet organization	1	234.1×	0.008	CIDEC
negative regulation of lipid catabolic process	1	210.7×	0.008	CIDEC
execution phase of apoptosis	1	191.5×	0.008	CIDEC
inflammatory response	2	18.9×	0.008	IL17RC, IL17RE
lipid storage	1	135.9×	0.009	CIDEC
positive regulation of cytokine production involved in inflammatory response	1	135.9×	0.009	IL17RC
defense response to fungus	1	110.9×	0.010	IL17RC
positive regulation of interleukin-6 production	1	41.7×	0.025	IL17RC
apoptotic process	1	7.2×	0.132	CIDEC

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 4

Druggability breadth: 1 of 4 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
IL17RC	0	0
CRELD1	0	0
IL17RE	0	0
CIDEC	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
IL17RE	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	IL17RC, CRELD1, IL17RE, CIDEC

Undrugged target profiles

4 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
IL17RC	0	—
CRELD1	0	—
IL17RE	2	—
CIDEC	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.