TLE3

Chr 15

TLE family member 3, transcriptional corepressor

Also known as: ESG, ESG3, GRG3, HsT18976

NCBI Gene: 7090 ENSG00000140332 UniProt: Q04726 OMIM: 600190

This gene encodes a transcriptional co-repressor protein that belongs to the transducin-like enhancer family of proteins. The members of this family function in the Notch signaling pathway that regulates determination of cell fate during development. Expression of this gene has been associated with a favorable outcome to chemotherapy with taxanes for ovarian carcinoma. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Sep 2013]

OMIM Research

OMIM ResearchGenerating clinical summary…

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.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.07

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.07LOEUF

pLI 1.000

Z-score 5.91

OE 0.00 (0.00–0.07)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

3.72Z-score

OE missense 0.52 (0.47–0.58)

246 obs / 474.0 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.07)

0≤0.351.4

Missense OE?0.52 (0.47–0.58)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 0 / 40.7Missense obs/exp: 246 / 474.0Syn Z: -1.08

Background carrier burden — how many people carry a rare variant somewhere in TLE3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

758 rare PASS variants

Rare truncating (LoF)

1 in 1,300

59 rare PASS variants

Rare synonymous (reference)

1 in 43

489 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TLE3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 180	1 in 2,000
South Asian	~43k	1 in 98	1 in 1,100
Remaining (unassigned)	~30k	1 in 85	1 in 920
European (Finnish)	~27k	1 in 170	1 in 5,200
Admixed American	~22k	1 in 130	1 in 2,400
African / African American	~21k	1 in 97	1 in 860
East Asian	~20k	1 in 130	1 in 2,800
Ashkenazi Jewish	~13k	1 in 350	1 in 2,600
Middle Eastern	~2,884	1 in 100	1 in 470

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 19 of 20 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 20.? see exons ↓