Candidiasis, familial, 8

Summary

Candidiasis, familial, 8 (MONDO:0014230) is a disease caused by TRAF3IP2 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: TRAF3IP2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 282

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	candidiasis, familial, 8
Mondo ID	MONDO:0014230
OMIM	615527
UMLS	C3714992
MedGen	811541
GARD	0015981
Is cancer (heuristic)	no

Also known as: CANDF8 · candidiasis, familial, 8 · candidiasis, familial, type 8 · chronic mucocutaneous candidiasis (disease) caused by mutation in TRAF3IP2 · TRAF3IP2 chronic mucocutaneous candidiasis (disease)

Data availability: 282 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, 8

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, 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

282 retrieved; paginated sample, class counts are floors:

130 uncertain significance, 115 likely benign, 13 pathogenic, 13 benign, 6 likely pathogenic, 3 conflicting classifications of pathogenicity, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2026969	NM_147686.4(TRAF3IP2):c.724C>T (p.Gln242Ter)	LOC114803478	Pathogenic	criteria provided, single submitter
2083346	NM_147686.4(TRAF3IP2):c.349del (p.Ala117fs)	LOC114803478	Pathogenic	criteria provided, single submitter
2909049	NM_147686.4(TRAF3IP2):c.698_749del (p.Ser233fs)	LOC114803478	Pathogenic	criteria provided, single submitter
1036337	NM_147686.4(TRAF3IP2):c.926_1022+148delinsTGACCTGAAAAGTCTATATTGGGCATTCCACTATGTGACTTGCTCACTAACGTGGGTTAGCAAACCTATAGAGAATTCTGTTACATCTTCATTGCATTGGCATAATTCCTTTCCATGTTAAAAATGCCTGAAGGTTGGGCCTGTCATACTTACTGGTGCCTTGGAAGCCCCGGAAAGGAGCAGTCTCTCTGTGCGGGCCTCTCTTCGTGGTCCCAGGGGCTGGGATAATTCAGGATAACCTTCTGCACAG	TRAF3IP2	Pathogenic	criteria provided, single submitter
1054010	NM_147686.4(TRAF3IP2):c.1222del (p.Ser408fs)	TRAF3IP2	Pathogenic	criteria provided, single submitter
2167641	NM_147686.4(TRAF3IP2):c.1471C>T (p.Arg491Ter)	TRAF3IP2	Pathogenic	criteria provided, single submitter
2414357	NM_147686.4(TRAF3IP2):c.7C>T (p.Arg3Ter)	TRAF3IP2	Pathogenic	criteria provided, single submitter
3616939	NM_147686.4(TRAF3IP2):c.1392del (p.Lys465fs)	TRAF3IP2	Pathogenic	criteria provided, single submitter
3625944	NM_147686.4(TRAF3IP2):c.973G>T (p.Glu325Ter)	TRAF3IP2	Pathogenic	criteria provided, single submitter
3718612	NM_147686.4(TRAF3IP2):c.847C>T (p.Arg283Ter)	TRAF3IP2	Pathogenic	criteria provided, single submitter
4808700	NM_147686.4(TRAF3IP2):c.395C>G (p.Ser132Ter)	TRAF3IP2	Pathogenic	criteria provided, single submitter
658088	NM_147686.4(TRAF3IP2):c.1044_1084del (p.Pro349fs)	TRAF3IP2	Pathogenic	criteria provided, single submitter
88768	NM_147686.4(TRAF3IP2):c.1580C>T (p.Thr527Ile)	TRAF3IP2	Pathogenic	no assertion criteria provided
2177771	NM_147686.4(TRAF3IP2):c.1201+1G>C	TRAF3IP2	Likely pathogenic	criteria provided, single submitter
2787870	NM_147686.4(TRAF3IP2):c.1201+2T>C	TRAF3IP2	Likely pathogenic	criteria provided, single submitter
3246037	NC_000006.11:g.(?111887655)(111890372_?)del	TRAF3IP2	Likely pathogenic	criteria provided, single submitter
4746317	NM_147686.4(TRAF3IP2):c.1201+1G>A	TRAF3IP2	Likely pathogenic	criteria provided, single submitter
2075669	NM_147686.4(TRAF3IP2):c.1290+1_1290+2del	TRAF3IP2-AS1	Likely pathogenic	criteria provided, single submitter
3700414	NM_147686.4(TRAF3IP2):c.1202-2A>G	TRAF3IP2-AS1	Likely pathogenic	criteria provided, single submitter
626192	NM_147686.4(TRAF3IP2):c.819C>G (p.His273Gln)	LOC114803478	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
720205	NM_147686.4(TRAF3IP2):c.232C>G (p.Arg78Gly)	LOC114803478	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1361311	NM_147686.4(TRAF3IP2):c.83C>T (p.Pro28Leu)	TRAF3IP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1008771	NM_147686.4(TRAF3IP2):c.583A>G (p.Ile195Val)	LOC114803478	Uncertain significance	criteria provided, single submitter
1009291	NM_147686.4(TRAF3IP2):c.566G>A (p.Gly189Asp)	LOC114803478	Uncertain significance	criteria provided, single submitter
1013996	NM_147686.4(TRAF3IP2):c.517G>A (p.Gly173Ser)	LOC114803478	Uncertain significance	criteria provided, single submitter
1019055	NM_147686.4(TRAF3IP2):c.542C>T (p.Pro181Leu)	LOC114803478	Uncertain significance	criteria provided, single submitter
1024424	NM_147686.4(TRAF3IP2):c.531G>A (p.Met177Ile)	LOC114803478	Uncertain significance	criteria provided, single submitter
1040300	NM_147686.4(TRAF3IP2):c.580A>G (p.Thr194Ala)	LOC114803478	Uncertain significance	criteria provided, single submitter
1041541	NM_147686.4(TRAF3IP2):c.822G>C (p.Gln274His)	LOC114803478	Uncertain significance	criteria provided, multiple submitters, no conflicts
1041546	NM_147686.4(TRAF3IP2):c.409C>T (p.Arg137Cys)	LOC114803478	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
TRAF3IP2	Strong	Autosomal recessive	candidiasis, familial, 8	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRAF3IP2	Orphanet:1334	Chronic mucocutaneous candidiasis

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TRAF3IP2	HGNC:1343	ENSG00000056972	O43734	E3 ubiquitin ligase TRAF3IP2	gencc,clinvar
TRAF3IP2-AS1	HGNC:40005	ENSG00000231889		TRAF3IP2 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRAF3IP2	E3 ubiquitin ligase TRAF3IP2	E3 ubiquitin ligase that catalyzes ‘Lys-63’-linked polyubiquitination of target protein, enhancing protein-protein interaction and cell signaling.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRAF3IP2	Other/Unknown	no		SEFIR_dom, E3_ubiq_ligase_TRAF3IP2
TRAF3IP2-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	1
oocyte	1
skin of leg	1
cortical plate	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRAF3IP2	266	ubiquitous	marker	cartilage tissue, oocyte, skin of leg
TRAF3IP2-AS1	191	ubiquitous	yes	cortical plate, ventricular zone, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRAF3IP2	1,463
TRAF3IP2-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TRAF3IP2	O43734	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
transitional two stage B cell differentiation	1	16852.0×	1e-03	TRAF3IP2
eosinophil mediated immunity	1	16852.0×	1e-03	TRAF3IP2
B cell affinity maturation	1	8426.0×	1e-03	TRAF3IP2
protein localization to P-body	1	8426.0×	1e-03	TRAF3IP2
leukocyte activation involved in inflammatory response	1	5617.3×	1e-03	TRAF3IP2
eosinophil homeostasis	1	5617.3×	1e-03	TRAF3IP2
T-helper 17 type immune response	1	3370.4×	0.001	TRAF3IP2
interleukin-17A-mediated signaling pathway	1	2808.7×	0.001	TRAF3IP2
establishment of T cell polarity	1	1872.4×	0.002	TRAF3IP2
type 2 immune response	1	1872.4×	0.002	TRAF3IP2
CD40 signaling pathway	1	1685.2×	0.002	TRAF3IP2
interleukin-17-mediated signaling pathway	1	1685.2×	0.002	TRAF3IP2
B cell apoptotic process	1	1404.3×	0.002	TRAF3IP2
mucus secretion	1	1296.3×	0.002	TRAF3IP2
neutrophil activation	1	991.3×	0.002	TRAF3IP2
lymph node development	1	802.5×	0.003	TRAF3IP2
signal transduction involved in regulation of gene expression	1	702.2×	0.003	TRAF3IP2
B cell homeostasis	1	561.7×	0.003	TRAF3IP2
positive regulation of defense response to virus by host	1	526.6×	0.003	TRAF3IP2
skin development	1	443.5×	0.004	TRAF3IP2
spleen development	1	401.2×	0.004	TRAF3IP2
T cell differentiation	1	383.0×	0.004	TRAF3IP2
mRNA stabilization	1	366.4×	0.004	TRAF3IP2
tumor necrosis factor-mediated signaling pathway	1	330.4×	0.004	TRAF3IP2
humoral immune response	1	280.9×	0.005	TRAF3IP2
protein K63-linked ubiquitination	1	267.5×	0.005	TRAF3IP2
protein import into nucleus	1	144.0×	0.008	TRAF3IP2
kidney development	1	140.4×	0.008	TRAF3IP2
heart development	1	78.8×	0.014	TRAF3IP2
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.015	TRAF3IP2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TRAF3IP2	0	0
TRAF3IP2-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	2	TRAF3IP2, TRAF3IP2-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TRAF3IP2	0	—
TRAF3IP2-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.