EGR2

Chr 10ADAR

early growth response 2

Also known as: AT591, CMT1D, CMT4E, KROX20

This transcription factor contains three tandem C2H2-type zinc fingers and regulates myelination in peripheral nerves. Mutations cause Charcot-Marie-Tooth disease types 1D and 4E, Dejerine-Sottas syndrome, and congenital hypomyelinating neuropathy type 1, with inheritance patterns that are autosomal dominant or autosomal recessive depending on the specific mutation. The pathogenic mechanism involves loss of function, leading to defective peripheral nerve myelination.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismAD/ARLOEUF 0.603 OMIM phenotypes
Clinical SummaryEGR2
🧬
Gene-Disease Validity (ClinGen)
Charcot-Marie-Tooth disease · SDDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.50) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
34 unique Pathogenic / Likely Pathogenic· 279 VUS of 486 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — EGR2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.60LOEUF
pLI 0.503
Z-score 2.42
OE 0.19 (0.080.60)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
2.44Z-score
OE missense 0.60 (0.530.68)
175 obs / 292.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.19 (0.080.60)
00.351.4
Missense OE0.60 (0.530.68)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 2 / 10.4Missense obs/exp: 175 / 292.6Syn Z: -0.58
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveEGR2-related neuropathy, congenital hypomyelinatingLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.5575th %ile
GOF
0.3986th %ile
LOF
0.76top 10%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNWe also contrast morphological studies in the context of the I268N homozygous recessive mutation affecting the NAB repressor binding site and the R359W dominant-negative mutation in the zinc-finger domain.PMID:17717711

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

486 submitted variants in ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic7
VUS279
Likely Benign138
Benign15
Conflicting18
27
Pathogenic
7
Likely Pathogenic
279
VUS
138
Likely Benign
15
Benign
18
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
13
14
0
27
Likely Pathogenic
0
6
1
0
7
VUS
11
249
19
0
279
Likely Benign
0
3
16
119
138
Benign
0
0
14
1
15
Conflicting
18
Total1127164120484

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

View in ClinVar →

Protein Context — Lollipop Plot

EGR2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →