EGR2: Early Growth Response 2 Gene
A key transcription factor in peripheral nervous system development and myelination
Gene Information Card
| Symbol | EGR2 |
|---|---|
| Full Name | Early growth response 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q21.3 |
| NCBI Gene ID | 1959 ncbi.nlm.nih.gov/gene/1959 |
| Ensembl ID | ENSG00000122877 |
| UniProt ID | P11161 |
| OMIM ID | 129010 |
| HGNC ID | 3239 |
| Aliases | KROX20, CMT1D, CMT4E, EGR-2, Krox-20 |
Description
EGR2 (early growth response 2) encodes a zinc-finger transcription factor that is essential for peripheral nervous system myelination and hindbrain segmentation. It regulates the expression of myelin-related genes in Schwann cells and plays a critical role in nerve development and regeneration. Mutations in EGR2 are associated with several hereditary peripheral neuropathies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Charcot-Marie-Tooth disease type 1D (CMT1D) | Dominant-negative or loss-of-function mutations impair Schwann cell differentiation and myelin gene expression, leading to demyelinating neuropathy. | ClinVar, OMIM |
| Charcot-Marie-Tooth disease type 4E (CMT4E) | Biallelic loss-of-function mutations disrupt myelination, causing severe early-onset neuropathy. | ClinVar, OMIM |
| Dejerine-Sottas syndrome (DSS) | Heterozygous or homozygous mutations in EGR2 cause severe hypomyelination and delayed motor development. | ClinVar, OMIM |
| Congenital hypomyelinating neuropathy (CHN) | Null mutations lead to complete absence of myelin, resulting in severe neonatal hypotonia and respiratory failure. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 5.2 | Low |
| Peripheral nerve | 28.1 | High |
| Spinal cord | 12.4 | Medium |
| Skeletal muscle | 1.8 | Not detected |
| Heart | 0.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Schwann cells (primary) | 35.6 | High expression; key for myelination |
| SH-SY5Y (neuroblastoma) | 8.3 | Moderate expression |
| HeLa (cervical carcinoma) | 2.1 | Low expression |
| HEK293 (embryonic kidney) | 1.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1003C>T (p.Arg335Trp) | Missense | Rare | Dominant-negative; disrupts DNA binding; associated with CMT1D |
| c.1081G>A (p.Asp361Asn) | Missense | Rare | Gain-of-function?; reported in DSS |
| c.1120_1122del (p.Lys374del) | Deletion | Rare | Loss-of-function; causes CMT4E |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss-of-function; congenital hypomyelinating neuropathy |
Mutation functional classification
Loss of Function (LOF)
Biallelic null or start-loss mutations abolish EGR2 activity, leading to severe hypomyelination (CMT4E, CHN).
Gain of Function (GOF)
Some missense mutations (e.g., p.Asp361Asn) may enhance transcriptional repression, but evidence is limited; classified as uncertain.
Dominant Negative (DN)
Heterozygous missense mutations (e.g., p.Arg335Trp) interfere with wild-type EGR2 function, causing CMT1D.
View complete mutation data：
Gene Ontology (GO)
Pathways
• MAPK signaling pathway (Reactome: R-HSA-5673001)
• Signaling by NTRK1 (TRKA) (Reactome: R-HSA-187037)
• Regulation of Schwann cell differentiation (KEGG: hsa04510)
Protein Summary
EGR2 (also known as Krox20) is a 476-amino-acid zinc-finger transcription factor that binds to GC-rich DNA sequences (EGR response elements). It is predominantly expressed in Schwann cells and specific hindbrain rhombomeres. EGR2 directly activates myelin-associated genes such as MPZ, PMP22, and MBP, and is required for the transition from promyelinating to myelinating Schwann cells. Its C-terminal zinc-finger domain mediates DNA binding, while the N-terminal region contains activation and repression domains. Mutations in EGR2 cause a spectrum of peripheral neuropathies, from mild CMT1D to lethal congenital hypomyelinating neuropathy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EGR2 Knockout HEK293 Cell Line | EDJ-KQ17870 | Human | 1959 | Details Get a Quote |
| EGR2 Knockout HeLa Cell Line | EDJ-KQ53146 | Human | 1959 | Details Get a Quote |
| EGR2 Knockout A-549 Cell Line | EDJ-KQ61619 | Human | 1959 | Details Get a Quote |
| EGR2 Knockout HCT 116 Cell Line | EDJ-KQ70106 | Human | 1959 | Details Get a Quote |
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