EGR2

Chr 10ADAR

early growth response 2

Also known as: AT591, CMT1D, CMT4E, KROX20

NCBI Gene: 1959ENSG00000122877UniProt: P11161

The protein encoded by this gene is a transcription factor with three tandem C2H2-type zinc fingers. Defects in this gene are associated with Charcot-Marie-Tooth disease type 1D (CMT1D), Charcot-Marie-Tooth disease type 4E (CMT4E), and with Dejerine-Sottas syndrome (DSS). Multiple transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, type 1DMIM #607678
AD
Dejerine-Sottas diseaseMIM #145900
ADAR
Hypomyelinating neuropathy, congenital, 1MIM #605253
ADAR
UniProtDejerine-Sottas syndrome
482
ClinVar variants
34
Pathogenic / LP
0.50
pLI score
1
Active trials
Clinical Summary— EGR2
🧬
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 Pathogenic / Likely Pathogenic· 278 VUS of 482 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.60LOEUF
pLI 0.503
Z-score 2.42
OE 0.19 (0.08–0.60)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.44Z-score
OE missense 0.60 (0.53–0.68)
175 obs / 292.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.19 (0.08–0.60)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.60 (0.53–0.68)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 2 / 10.4Missense obs/exp: 175 / 292.6Syn Z: -0.58

ClinVar Variant Classifications

482 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic7
VUS278
Likely Benign137
Benign15
Conflicting18
27
Pathogenic
7
Likely Pathogenic
278
VUS
137
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
7
235
36
0
278
Likely Benign
0
3
16
118
137
Benign
0
0
14
1
15
Conflicting
—18
Total725781119482

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.

Gene2Phenotype Curations

EGR2-related neuropathy, congenital hypomyelinating

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Charcot-Marie-Tooth disease, type 1D

MIM #607678

Molecular basis of disorder known

Autosomal dominant

Dejerine-Sottas disease

MIM #145900

Molecular basis of disorder known

Autosomal dominantAutosomal recessive

Hypomyelinating neuropathy, congenital, 1

MIM #605253

Molecular basis of disorder known

Autosomal dominantAutosomal recessive
📖
GeneReview available — EGR2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Uveitis genetics.
Hou S et al.·Exp Eye Res
2020Review
Transcription factor EGR2 alleviates autoimmune uveitis via activation of GDF15 to modulate the retinal microglial phenotype.
Li W et al.·Proc Natl Acad Sci U S A
2024
Inherited peripheral neuropathy.
Keller MP et al.·Semin Neurol
1999Review
Transcription factor EGR2 controls homing and pathogenicity of T(H)17 cells in the central nervous system.
Gao Y et al.·Nat Immunol
2023
[Hereditary peripheral neuropathies].
Vallat JM et al.·Presse Med
2009Review
Chromatin Remodeling in Patient-Derived Colorectal Cancer Models.
Xiang K et al.·Adv Sci (Weinh)
2024Functional
Transcription factor EGR2 drives cataract formation through IGFBP3-mediated oxidative injury in lens epithelial cells.
Li W et al.·Free Radic Biol Med
2025
Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis.
Palencia-Campos A et al.·J Nanobiotechnology
2024
EGR2-related mixed demyelinating and axonal Charcot-Marie-Tooth disease: An electrodiagnostic, nerve imaging, and histological study.
Chu XJ et al.·Clin Neuropathol
2022
Comprehensive genetic analysis by targeted sequencing identifies risk factors and predicts patient outcome in Mantle Cell Lymphoma: results from the EU-MCL network trials.
Khouja M et al.·Leukemia
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Obstructive Sleep Apnea-Hypopnea SyndromeAnxiety DisordersDepressive Disorders

EGR2 and NLRP3 Pathways in Obstructive Sleep Apnea-Related Cognitive and Mood Disorders

RECRUITING
NCT07120711Xinhua Hospital, Shanghai Jiao Tong University School of MedicineStarted 2025-07-01
EGR2/NLRP3 pathway activityfatty tissue

External Resources

Links to major genomics databases and tools