LEF1

Chr 4AD

lymphoid enhancer binding factor 1

Also known as: ECTD1, ECTD17, LEF-1, TCF10, TCF1ALPHA, TCF7L3

NCBI Gene: 51176ENSG00000138795UniProt: Q9UJU2OMIM: 153245

This gene encodes a transcription factor belonging to a family of proteins that share homology with the high mobility group protein-1. The protein encoded by this gene can bind to a functionally important site in the T-cell receptor-alpha enhancer, thereby conferring maximal enhancer activity. This transcription factor is involved in the Wnt signaling pathway, and it may function in hair cell differentiation and follicle morphogenesis. Mutations in this gene have been found in somatic sebaceous tumors. This gene has also been linked to other cancers, including androgen-independent prostate cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Ectodermal dysplasia 17 with or without limb malformationsMIM #621224
AD

Clinical highlights

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
219
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.21
LOEUF· LoF intol.
LOF
Mechanism· predicted
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GeneReview available — LEF1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.21LOEUF
pLI 0.998
Z-score 4.19
OE 0.04 (0.01–0.21)
Highly constrained

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

Missense Constraint?
1.57Z-score
OE missense 0.71 (0.63–0.81)
167 obs / 234.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.04 (0.01–0.21)
0≤0.351.4
Missense OE?0.71 (0.63–0.81)
0≤0.61.4
Synonymous OE?0.96
0≤1.21.6
LoF obs/exp: 1 / 22.4Missense obs/exp: 167 / 234.8Syn Z: 0.28

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

LEF1 · 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