Chronic mucocutaneous candidiasis

Summary

Chronic mucocutaneous candidiasis (MONDO:0015279) is a disease (an umbrella term covering 12 Mondo subtypes) with 6 cohort genes and 3 clinical trials. The dominant Reactome pathway is SARS-CoV-2 activates/modulates innate and adaptive immune responses (4 cohort genes).

At a glance

• Prevalence: Unknown (Worldwide)
• Umbrella term: 12 Mondo subtypes
• Cohort genes: 6
• ClinVar variants: 3
• Phenotypes (HPO): 31
• Clinical trials: 3

Clinical features

Signs & symptoms

Clinical features (HPO)

31 HPO clinical features (Orphanet curated; top 31 by frequency):

HPO ID	Term	Frequency
HP:0000153	Abnormality of the mouth	Very frequent (80-99%)
HP:0000159	Abnormal lip morphology	Very frequent (80-99%)
HP:0000951	Abnormality of the skin	Very frequent (80-99%)
HP:0000962	Hyperkeratosis	Very frequent (80-99%)
HP:0000988	Skin rash	Very frequent (80-99%)
HP:0001231	Abnormal fingernail morphology	Very frequent (80-99%)
HP:0001597	Abnormality of the nail	Very frequent (80-99%)
HP:0001821	Broad nail	Very frequent (80-99%)
HP:0002715	Abnormality of the immune system	Very frequent (80-99%)
HP:0002719	Recurrent infections	Very frequent (80-99%)
HP:0008388	Abnormal toenail morphology	Very frequent (80-99%)
HP:0010783	Erythema	Very frequent (80-99%)
HP:0100825	Cheilitis	Very frequent (80-99%)
HP:0200042	Skin ulcer	Very frequent (80-99%)
HP:0000142	Abnormality of the vagina	Frequent (30-79%)
HP:0030016	Dyspareunia	Frequent (30-79%)
HP:0200034	Papule	Frequent (30-79%)
HP:0000010	Recurrent urinary tract infections	Occasional (5-29%)
HP:0000478	Abnormality of the eye	Occasional (5-29%)
HP:0000504	Abnormality of vision	Occasional (5-29%)
HP:0000682	Abnormality of dental enamel	Occasional (5-29%)
HP:0000790	Hematuria	Occasional (5-29%)
HP:0000989	Pruritus	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0002105	Hemoptysis	Occasional (5-29%)
HP:0002205	Recurrent respiratory infections	Occasional (5-29%)
HP:0004306	Abnormality of the endocardium	Occasional (5-29%)
HP:0004370	Abnormality of temperature regulation	Occasional (5-29%)
HP:0008872	Feeding difficulties in infancy	Occasional (5-29%)
HP:0012115	Hepatitis	Occasional (5-29%)
HP:0012735	Cough	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	chronic mucocutaneous candidiasis
Mondo ID	MONDO:0015279
MeSH	D002178
OMIM	114580
Orphanet	1334
DOID	DOID:2058
ICD-11	2120780687
NCIT	C34444
SNOMED CT	234568006
UMLS	C0006845
MedGen	2426
GARD	0001077
MedDRA	10009007
Is cancer (heuristic)	no

Also known as: CANDF · chronic mucocutaneous candidiasis · chronic mucocutaneous candidiasis (disease) · CMC · familial candidiasis · familial chronic mucocutaneous candidiasis · familial CMC

Data availability: 3 ClinVar variants · 5 GenCC gene-disease records · 1 HPO phenotype.

Disease family

An umbrella term covering 12 Mondo subtypes.

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

Related subtypes (40): B cell deficiency, complement deficiency, phagocyte bactericidal dysfunction, trichohepatoenteric syndrome, hepatic veno-occlusive disease-immunodeficiency syndrome, immunodeficiency with defective T-cell response to interleukin 1, Say-Barber-Miller syndrome, familial isolated congenital asplenia, X-linked immunoneurologic disorder, ectodermal dysplasia and immune deficiency, immunodeficiency 33, immunodeficiency 47, combined immunodeficiency due to moesin deficiency, immunodeficiency, X-linked, with deficiency of 115,000 Dalton surface glycoprotein, properdin deficiency, X-linked, combined immunodeficiency with faciooculoskeletal anomalies, recurrent infections associated with rare immunoglobulin isotypes deficiency, immunodeficiency 28, autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity, immunodeficiency 37, immunodeficiency 39, BENTA disease, primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection, immunodeficiency 49, hereditary hemophagocytic lymphohistiocytosis, immunoglobulin heavy chain deficiency, immuno-osseous dysplasia, lymphoproliferative syndrome, IL10-related early-onset inflammatory bowel disease, T-cell immunodeficiency with epidermodysplasia verruciformis, Aicardi-Goutieres syndrome, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, inflammatory bowel disease-recurrent sinopulmonary infections syndrome, A20 haploinsufficiency, NK cell deficiency, T cell and NK cell immunodeficiency, dendritic cell deficiency, immunodysregulation with variable immunodeficiency and autoimmunity, immune dysregulation with immunodeficiency due to AIOLOS haploinsufficiency, STAT5 haploinsufficiency

Subtypes (12): 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, candidiasis, familial, 9

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

3 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1264351	NM_007315.4(STAT1):c.884C>A (p.Thr295Lys)	STAT1	Pathogenic	no assertion criteria provided
30084	NM_007315.4(STAT1):c.800C>T (p.Ala267Val)	STAT1	Pathogenic	criteria provided, multiple submitters, no conflicts
3075957	NM_014339.7(IL17RA):c.599-1G>A	IL17RA	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 8 · 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
TRAF3IP2	Strong	Autosomal recessive	candidiasis, familial, 8	3
CLEC7A	Supportive	Autosomal dominant	chronic mucocutaneous candidiasis
IL17F	Supportive	Autosomal dominant	chronic mucocutaneous candidiasis	3
IL17RA	Supportive	Autosomal dominant	chronic mucocutaneous candidiasis	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IL17RA	Orphanet:1334	Chronic mucocutaneous candidiasis
TRAF3IP2	Orphanet:1334	Chronic mucocutaneous candidiasis
CLEC7A	Orphanet:1334	Chronic mucocutaneous candidiasis
IL17F	Orphanet:1334	Chronic mucocutaneous candidiasis
IL17RC	Orphanet:1334	Chronic mucocutaneous candidiasis
STAT1	Orphanet:319595	Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency
STAT1	Orphanet:391311	Susceptibility to viral and mycobacterial infections due to STAT1 deficiency
STAT1	Orphanet:391487	STAT1-related autoimmune enteropathy and endocrinopathy-susceptibility to chronic infections syndrome

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
IL17RA	HGNC:5985	ENSG00000177663	Q96F46	Interleukin-17 receptor A	gencc,clinvar
TRAF3IP2	HGNC:1343	ENSG00000056972	O43734	E3 ubiquitin ligase TRAF3IP2	gencc
CLEC7A	HGNC:14558	ENSG00000172243	Q9BXN2	C-type lectin domain family 7 member A	gencc
IL17F	HGNC:16404	ENSG00000112116	Q96PD4	Interleukin-17F	gencc
IL17RC	HGNC:18358	ENSG00000163702	Q8NAC3	Interleukin-17 receptor C	gencc
STAT1	HGNC:11362	ENSG00000115415	P42224	Signal transducer and activator of transcription 1-alpha/beta	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IL17RA	Interleukin-17 receptor A	Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity.
TRAF3IP2	E3 ubiquitin ligase TRAF3IP2	E3 ubiquitin ligase that catalyzes ‘Lys-63’-linked polyubiquitination of target protein, enhancing protein-protein interaction and cell signaling.
CLEC7A	C-type lectin domain family 7 member A	Lectin that functions as a pattern recognizing receptor (PRR) specific for beta-1,3-linked and beta-1,6-linked glucans, which constitute cell wall constituents from pathogenic bacteria and fungi.
IL17F	Interleukin-17F	Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity.
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.
STAT1	Signal transducer and activator of transcription 1-alpha/beta	Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 5 · 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	5	1.5×	0.348
Transcription factor	1	1.4×	0.539

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IL17RA	Other/Unknown	no		SEFIR_dom, IL17R_A/B_N, IL17RA/B_FnIII-like_1_sf
TRAF3IP2	Other/Unknown	no		SEFIR_dom, E3_ubiq_ligase_TRAF3IP2
CLEC7A	Other/Unknown	no		C-type_lectin-like, C-type_lectin-like/link_sf, CTDL_fold
IL17F	Other/Unknown	no		IL-17_fam, IL-17_chr, Cystine-knot_cytokine
IL17RC	Other/Unknown	no		SEFIR_dom, IL-17_rcpt_C/E_N, IL-17_rcpt-like
STAT1	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf

Expression context

Cohort genes with no expression data: 0.

5 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
leukocyte	2
monocyte	2
mononuclear cell	2
blood	1
cartilage tissue	1
oocyte	1
skin of leg	1
endothelial cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
adenohypophysis	1
right adrenal gland cortex	1
right lobe of liver	1
epithelium of nasopharynx	1
vermiform appendix	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IL17RA	262	ubiquitous	marker	blood, monocyte, leukocyte
TRAF3IP2	266	ubiquitous	marker	cartilage tissue, oocyte, skin of leg
CLEC7A	249	broad	marker	monocyte, mononuclear cell, leukocyte
IL17F	43		yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, endothelial cell
IL17RC	244	ubiquitous	marker	adenohypophysis, right lobe of liver, right adrenal gland cortex
STAT1	294	ubiquitous	marker	epithelium of nasopharynx, vermiform appendix, mononuclear cell

Protein interactions among cohort

Intra-cohort edges: 5.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STAT1	6,459
CLEC7A	2,364
IL17RA	2,226
IL17F	1,523
TRAF3IP2	1,463
IL17RC	1,020

Intra-cohort edges

A	B	Sources
IL17F	IL17RA	intact, string_interaction
IL17F	IL17RC	intact, string_interaction
IL17RA	IL17RC	string_interaction
IL17RA	TRAF3IP2	biogrid_interaction, string_interaction
IL17RC	TRAF3IP2	biogrid_interaction, string_interaction

Structural data

PDB: 5 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IL17RA	Q96F46	10
STAT1	P42224	10
IL17F	Q96PD4	9
IL17RC	Q8NAC3	5
TRAF3IP2	O43734	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CLEC7A	Q9BXN2	77.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 66. Enrichment computed across 6 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
SARS-CoV-2 activates/modulates innate and adaptive immune responses	4	71.4×	5e-06	IL17RA, STAT1, IL17F, IL17RC
Interleukin-17 signaling	3	152.3×	2e-05	IL17RA, IL17F, IL17RC
Interleukin-4 and Interleukin-13 signaling	2	41.1×	0.020	STAT1, IL17F
Signaling by PDGFR in disease	1	326.3×	0.025	STAT1
Interleukin-6 family signaling	1	285.5×	0.025	STAT1
Interleukin-9 signaling	1	253.8×	0.025	STAT1
FGFR1 mutant receptor activation	1	228.4×	0.025	STAT1
Interleukin-21 signaling	1	228.4×	0.025	STAT1
Signaling by KIT in disease	1	228.4×	0.025	STAT1
Interleukin-27 signaling	1	207.6×	0.025	STAT1
Interleukin-6 signaling	1	190.3×	0.025	STAT1
Interleukin-35 Signalling	1	190.3×	0.025	STAT1
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	1	175.7×	0.025	STAT1
Signaling by PDGFRA extracellular domain mutants	1	175.7×	0.025	STAT1
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)	1	175.7×	0.025	STAT1
Regulation of IFNG signaling	1	163.1×	0.025	STAT1
Signaling by cytosolic FGFR1 fusion mutants	1	126.9×	0.028	STAT1
Interleukin-2 family signaling	1	126.9×	0.028	STAT1
Signaling by CSF3 (G-CSF)	1	114.2×	0.028	STAT1
Signaling by NOTCH3	1	103.8×	0.028	STAT1
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	1	103.8×	0.028	STAT1
Interleukin-12 family signaling	1	95.2×	0.028	STAT1
Growth hormone receptor signaling	1	95.2×	0.028	STAT1
NOTCH3 Intracellular Domain Regulates Transcription	1	87.8×	0.028	STAT1
Regulation of IFNA/IFNB signaling	1	87.8×	0.028	STAT1
Inactivation of CSF3 (G-CSF) signaling	1	87.8×	0.028	STAT1
Signaling by FGFR in disease	1	84.6×	0.028	STAT1
Interleukin-20 family signaling	1	84.6×	0.028	STAT1
Downstream signal transduction	1	76.1×	0.030	STAT1
Downregulation of SMAD2/3:SMAD4 transcriptional activity	1	73.7×	0.030	STAT1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of cytokine production involved in inflammatory response	4	362.4×	2e-08	IL17RA, CLEC7A, IL17F, IL17RC
interleukin-17A-mediated signaling pathway	3	1404.3×	4e-08	IL17RA, TRAF3IP2, IL17RC
interleukin-17-mediated signaling pathway	3	842.6×	1e-07	IL17RA, TRAF3IP2, IL17F
positive regulation of interleukin-6 production	4	111.2×	6e-07	IL17RA, CLEC7A, IL17F, IL17RC
inflammatory response	5	31.4×	2e-06	IL17RA, TRAF3IP2, CLEC7A, IL17F, IL17RC
granulocyte chemotaxis	2	1123.5×	2e-05	IL17RA, IL17RC
T-helper 17 type immune response	2	1123.5×	2e-05	IL17RA, TRAF3IP2
positive regulation of chemokine (C-X-C motif) ligand 1 production	2	936.2×	3e-05	IL17RA, IL17F
positive regulation of interleukin-23 production	2	802.5×	3e-05	IL17RA, CLEC7A
positive regulation of defense response to virus by host	2	175.5×	7e-04	STAT1, TRAF3IP2
positive regulation of nitric oxide biosynthetic process	2	151.8×	9e-04	STAT1, CLEC7A
defense response to fungus	2	147.8×	9e-04	IL17RA, IL17RC
tumor necrosis factor-mediated signaling pathway	2	110.1×	0.001	STAT1, TRAF3IP2
transitional two stage B cell differentiation	1	2808.7×	0.002	TRAF3IP2
eosinophil mediated immunity	1	2808.7×	0.002	TRAF3IP2
detection of molecule of fungal origin	1	2808.7×	0.002	CLEC7A
regulation of granulocyte macrophage colony-stimulating factor production	1	2808.7×	0.002	IL17F
positive regulation of lymphocyte activation	1	2808.7×	0.002	CLEC7A
negative regulation of metanephric nephron tubule epithelial cell differentiation	1	2808.7×	0.002	STAT1
positive regulation of cell maturation	1	2808.7×	0.002	CLEC7A
detection of yeast	1	1404.3×	0.003	CLEC7A
positive regulation of antimicrobial peptide production	1	1404.3×	0.003	IL17F
B cell affinity maturation	1	1404.3×	0.003	TRAF3IP2
negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis	1	1404.3×	0.003	STAT1
carbohydrate mediated signaling	1	1404.3×	0.003	CLEC7A
detection of fungus	1	1404.3×	0.003	CLEC7A
regulation of interleukin-2 production	1	1404.3×	0.003	IL17F
negative regulation by virus of viral protein levels in host cell	1	1404.3×	0.003	STAT1
protein localization to P-body	1	1404.3×	0.003	TRAF3IP2
negative regulation of angiogenesis	2	56.2×	0.003	STAT1, IL17F

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Amphotericin B.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 5

Druggability breadth: 5 of 6 evidence-associated genes (83%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
STAT1	FILGOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
STAT1	5	4
IL17RA	0	0
TRAF3IP2	0	0
CLEC7A	0	0
IL17F	0	0
IL17RC	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FILGOTINIB	4	STAT1
DEUCRAVACITINIB	4	STAT1
EPIGALOCATECHIN GALLATE	3	STAT1
SURAMIN HEXASODIUM	3	STAT1
IPRIFLAVONE	2	STAT1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
STAT1	147	Binding:137, Functional:8, Unclassified:2
CLEC7A	3	Binding:2, Functional:1
IL17F	2	Binding:2

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
STAT1	147

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

5 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.

Compound	Max phase	Cohort target (bioactivity)
FILGOTINIB	4	STAT1
DEUCRAVACITINIB	4	STAT1
EPIGALOCATECHIN GALLATE	3	STAT1
SURAMIN HEXASODIUM	3	STAT1
IPRIFLAVONE	2	STAT1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	STAT1
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	5	IL17RA, TRAF3IP2, CLEC7A, IL17F, IL17RC

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
IL17RA	0	—
TRAF3IP2	0	—
CLEC7A	3	—
IL17F	2	—
IL17RC	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3

Top trials by phase / activity

NCT	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