TFE3

Chr X

transcription factor binding to IGHM enhancer 3

Also known as: MRXSPF, RCCP2, RCCX1, TFEA, bHLHe33

NCBI Gene: 7030ENSG00000068323UniProt: P19532

This gene encodes a basic helix-loop-helix domain-containing transcription factor that binds MUE3-type E-box sequences in the promoter of genes. The encoded protein promotes the expression of genes downstream of transforming growth factor beta (TGF-beta) signaling. This gene may be involved in chromosomal translocations in renal cell carcinomas and other cancers, resulting in the production of fusion proteins. Translocation partners include PRCC (papillary renal cell carcinoma), NONO (non-POU domain containing, octamer-binding), and ASPSCR1 (alveolar soft part sarcoma chromosome region, candidate 1), among other genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies
UniProtRenal cell carcinoma Xp11-associated

Clinical highlights

Gene-disease validity (ClinGen)
X-linked syndromic complex neurodevelopmental disorder · XLDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
311
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.29
LOEUF· LoF intol.
LOF
Mechanism· predicted
📖
GeneReview available — TFE3
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.29LOEUF
pLI 0.980
Z-score 3.52
OE 0.06 (0.02–0.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.15Z-score
OE missense 0.60 (0.52–0.69)
140 obs / 232.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.06 (0.02–0.29)
0≤0.351.4
Missense OE?0.60 (0.52–0.69)
0≤0.61.4
Synonymous OE?0.90
0≤1.21.6
LoF obs/exp: 1 / 16.3Missense obs/exp: 140 / 232.4Syn Z: 0.83

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TFE3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients