TFE3

Chr XX-linked

transcription factor binding to IGHM enhancer 3

TFE3 encodes a transcription factor that regulates lysosomal biogenesis and cellular responses to nutrient availability by binding to specific DNA sequences and promoting expression of lysosomal genes. Mutations cause X-linked intellectual developmental disorder with syndromic features including pigmentary mosaicism and coarse facies. The gene follows X-linked inheritance and is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.29).

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismX-linkedLOEUF 0.292 OMIM phenotypes
Clinical SummaryTFE3
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Gene-Disease Validity (ClinGen)
X-linked syndromic complex neurodevelopmental disorder · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.980
Z-score 3.52
OE 0.06 (0.020.29)
Highly constrained

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

Missense Constraint
2.15Z-score
OE missense 0.60 (0.520.69)
140 obs / 232.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.06 (0.020.29)
00.351.4
Missense OE0.60 (0.520.69)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 1 / 16.3Missense obs/exp: 140 / 232.4Syn Z: 0.83
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTFE3-related intellectual disability with pigmentary mosaicism and coarse featuresOTHERmonoallelic_X_heterozygous
DN
0.3892th %ile
GOF
0.3391th %ile
LOF
0.79top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.29

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in 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.

3D Protein StructureAlphaFold
Clinical Literature
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