renal cell carcinoma, Xp11-associated

Summary

renal cell carcinoma, Xp11-associated (MONDO:0010456) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver; 3 ClinVar predisposition records).

At a glance

• Classification: Cancer
• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	renal cell carcinoma, Xp11-associated
Mondo ID	MONDO:0010456
OMIM	300854
UMLS	C3275446
MedGen	477077
GARD	0018445
Is cancer (heuristic)	yes

Also known as: RCCX1 · renal cell carcinoma, papillary, 1 · renal cell carcinoma, Xp11-associated

Data availability: 3 ClinVar variants.

Disease family

Classification path: disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › adenocarcinoma › renal cell carcinoma › renal cell adenocarcinoma › hereditary renal cell carcinoma › renal cell carcinoma, Xp11-associated

Related subtypes (6): hereditary papillary renal cell carcinoma, adrenocortical carcinoma, hereditary, aniridia 2, aniridia 3, hereditary clear cell renal cell carcinoma, PAX6-related ocular dysgenesis

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 uncertain significance, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
2660498	NM_006521.6(TFE3):c.1592G>A (p.Gly531Glu)	TFE3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1330578	NM_006521.6(TFE3):c.1694G>A (p.Arg565His)	TFE3	Uncertain significance	criteria provided, single submitter
4080538	NM_006521.6(TFE3):c.1483C>T (p.Pro495Ser)	TFE3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
TFE3			CIViC #5734

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TFE3	Orphanet:157791	Epithelioid hemangioendothelioma
TFE3	Orphanet:163699	Alveolar soft tissue sarcoma
TFE3	Orphanet:319308	MiT family translocation renal cell carcinoma

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TFE3	HGNC:11752	ENSG00000068323	P19532	Transcription factor E3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TFE3	Transcription factor E3	Transcription factor that acts as a master regulator of lysosomal biogenesis and immune response.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TFE3	Transcription factor	no		bHLH_dom, MiT/TFE_C, bHLHzip_TFE3

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
dorsal motor nucleus of vagus nerve	1
inferior olivary complex	1
olfactory bulb	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TFE3	292	ubiquitous	marker	inferior olivary complex, dorsal motor nucleus of vagus nerve, olfactory bulb

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TFE3	2,278

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TFE3	P19532	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Transcriptional and post-translational regulation of MITF-M expression and activity	1	178.4×	0.013	TFE3
MITF-M-regulated melanocyte development	1	114.2×	0.013	TFE3
Developmental Biology	1	14.5×	0.069	TFE3

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
regulation of osteoclast differentiation	1	1532.0×	0.005	TFE3
positive regulation of brown fat cell differentiation	1	991.3×	0.005	TFE3
negative regulation of cold-induced thermogenesis	1	343.9×	0.006	TFE3
lysosome organization	1	306.4×	0.006	TFE3
humoral immune response	1	280.9×	0.006	TFE3
positive regulation of cell adhesion	1	271.8×	0.006	TFE3
adaptive immune response	1	84.3×	0.017	TFE3
positive regulation of DNA-templated transcription	1	27.9×	0.045	TFE3
positive regulation of transcription by RNA polymerase II	1	14.9×	0.075	TFE3
regulation of transcription by RNA polymerase II	1	11.7×	0.086	TFE3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TFE3	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
TFE3	3	Binding:3

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).

Drug repurposing candidates

0 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

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	1	TFE3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TFE3	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.