EGR3

Chr 8

early growth response 3

Also known as: EGR-3, PILOT

The protein is a transcription factor with C2H2-type zinc fingers that regulates gene expression controlling biological rhythms and is involved in muscle spindle development, muscle development, lymphocyte development, and neuronal development. Mutations cause autosomal dominant disorders, though specific associated diseases are not well-established in the provided data. This gene is highly constrained against loss-of-function variation (pLI 0.95, LOEUF 0.31), suggesting that haploinsufficiency is likely not tolerated.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
26
Pubs (1 yr)
83
P/LP submissions
0%
P/LP missense
0.31
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryEGR3
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
83 unique Pathogenic / Likely Pathogenic· 36 VUS of 130 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.31LOEUF
pLI 0.953
Z-score 2.87
OE 0.00 (0.000.31)
Highly constrained

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

Missense Constraint
3.38Z-score
OE missense 0.41 (0.350.48)
107 obs / 260.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.000.31)
00.351.4
Missense OE0.41 (0.350.48)
00.61.4
Synonymous OE0.84
01.21.6
LoF obs/exp: 0 / 9.6Missense obs/exp: 107 / 260.3Syn Z: 1.31
DN
0.3892th %ile
GOF
0.3094th %ile
LOF
0.86top 5%

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

LOFprediction above median · LOEUF 0.31

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

130 submitted variants in ClinVar

Classification Summary

Pathogenic79
Likely Pathogenic4
VUS36
Likely Benign4
Benign4
79
Pathogenic
4
Likely Pathogenic
36
VUS
4
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
79
0
79
Likely Pathogenic
0
0
4
0
4
VUS
1
26
9
0
36
Likely Benign
0
0
1
3
4
Benign
0
0
0
4
4
Total126937127

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

EGR3 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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