EGR2

early growth response 2, the group of Zinc fingers C2H2-type

Basic information

Region (hg38): 10:62811996-62819167

Previous symbols: [ "KROX20" ]

Links

ENSG00000122877NCBI:1959OMIM:129010HGNC:3239Uniprot:P11161AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • Charcot-Marie-Tooth disease type 4E (Definitive), mode of inheritance: AR
  • Charcot-Marie-Tooth disease type 1D (Strong), mode of inheritance: AD
  • Charcot-Marie-Tooth disease type 3 (Moderate), mode of inheritance: Semidominant
  • Charcot-Marie-Tooth disease type 4E (Limited), mode of inheritance: AR
  • Charcot-Marie-Tooth disease type 3 (Supportive), mode of inheritance: AD
  • Charcot-Marie-Tooth disease type 4E (Supportive), mode of inheritance: AR
  • Charcot-Marie-Tooth disease type 1D (Supportive), mode of inheritance: AD
  • Charcot-Marie-Tooth disease type 1D (Strong), mode of inheritance: AD
  • Charcot-Marie-Tooth disease (Definitive), mode of inheritance: Semidominant
  • Charcot-Marie-Tooth disease type 4E (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Charcot-Marie-Tooth disease, demyelinating, type 1D; Neuropathy, congenital hypomyelinating, 1, autosomal recessive; Dejerine-Sottas diseaseAD/ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic9537424; 10369870; 10371530; 11523566; 15947997; 21840889; 22271166; 22522483; 22546699; 22734907

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EGR2 gene.

  • Charcot-Marie-Tooth disease, type I (8 variants)
  • Charcot-Marie-Tooth disease type 1D (6 variants)
  • not provided (6 variants)
  • Charcot-Marie-Tooth disease (5 variants)
  • Dejerine-Sottas disease (4 variants)
  • Dejerine-sottas neuropathy, autosomal dominant (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EGR2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
98
clinvar
1
clinvar
99
missense
11
clinvar
4
clinvar
194
clinvar
2
clinvar
211
nonsense
3
clinvar
3
start loss
0
frameshift
5
clinvar
5
inframe indel
13
clinvar
13
splice donor/acceptor (+/-2bp)
0
splice region
3
3
non coding
14
clinvar
12
clinvar
10
clinvar
36
Total 11 4 229 112 11

Variants in EGR2

This is a list of pathogenic ClinVar variants found in the EGR2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
10-62812127-C-T Charcot-Marie-Tooth disease, type I Likely benign (Jun 14, 2016)300263
10-62812179-T-C Charcot-Marie-Tooth disease, type I Uncertain significance (Jun 14, 2016)300264
10-62812288-C-G Charcot-Marie-Tooth disease type 1D Uncertain significance (Jan 13, 2018)300265
10-62812333-T-C Charcot-Marie-Tooth disease type 1D Benign (Jan 13, 2018)300266
10-62812390-GAGA-G Charcot-Marie-Tooth disease, type I Uncertain significance (Jun 14, 2016)300267
10-62812552-C-T Charcot-Marie-Tooth disease type 1D Uncertain significance (Jan 13, 2018)300268
10-62812561-G-A Charcot-Marie-Tooth disease type 1D Uncertain significance (Jan 12, 2018)300269
10-62812589-A-G Charcot-Marie-Tooth disease type 1D Uncertain significance (Jan 13, 2018)878661
10-62812751-C-T Charcot-Marie-Tooth disease type 1D Uncertain significance (Jan 13, 2018)300270
10-62812778-C-T Charcot-Marie-Tooth disease type 1D Benign (Jan 12, 2018)300271
10-62812919-C-T Charcot-Marie-Tooth disease type 1D Benign/Likely benign (Jun 19, 2018)300272
10-62812920-A-T Charcot-Marie-Tooth disease type 1D Benign (Jun 16, 2018)300273
10-62812977-C-A Charcot-Marie-Tooth disease type 1D Uncertain significance (Jan 15, 2018)878662
10-62813057-T-C Charcot-Marie-Tooth disease type 1D Uncertain significance (Jan 13, 2018)878663
10-62813062-A-T Charcot-Marie-Tooth disease type 1D Uncertain significance (Jan 13, 2018)300274
10-62813128-G-T Charcot-Marie-Tooth disease type 1D Uncertain significance (Jan 13, 2018)879262
10-62813187-GTAT-G Likely benign (Jan 25, 2018)420319
10-62813208-C-G Charcot-Marie-Tooth disease, type I Uncertain significance (Apr 26, 2023)2988561
10-62813210-A-T Charcot-Marie-Tooth disease, type I Likely benign (Oct 07, 2022)695618
10-62813213-T-G Charcot-Marie-Tooth disease, type I Likely benign (Mar 26, 2022)1905680
10-62813217-C-T Charcot-Marie-Tooth disease, type I Uncertain significance (Jan 17, 2024)2721317
10-62813218-G-A Charcot-Marie-Tooth disease, type I Uncertain significance (Dec 02, 2021)1036056
10-62813220-G-A Inborn genetic diseases Uncertain significance (Feb 16, 2023)2485919
10-62813224-G-C Charcot-Marie-Tooth disease, type I Uncertain significance (Apr 20, 2020)841200
10-62813224-G-T Charcot-Marie-Tooth disease, type I Likely benign (Dec 30, 2023)2741870

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
EGR2protein_codingprotein_codingENST00000242480 2107905
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.5030.493125744041257480.0000159
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.441752930.5980.00001873049
Missense in Polyphen2862.8340.44562668
Synonymous-0.5841311231.070.000007971085
Loss of Function2.42210.40.1926.37e-7122

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00003530.0000352
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Sequence-specific DNA-binding transcription factor. Binds to two specific DNA sites located in the promoter region of HOXA4. {ECO:0000269|PubMed:21836637}.;
Disease
DISEASE: Neuropathy, congenital hypomyelinating or amyelinating (CHN) [MIM:605253]: A severe degenerating neuropathy that results from a congenital impairment in myelin formation. It is clinically characterized by early onset of hypotonia, areflexia, distal muscle weakness, and very slow nerve conduction velocities (as low as 3m/s). Some patients manifest nearly complete absence of spontaneous limb movements, respiratory distress at birth, and complete absence of myelin shown by electron microscopy of peripheral nerves. Inheritance can be autosomal dominant or recessive. {ECO:0000269|PubMed:22522483, ECO:0000269|PubMed:9537424}. Note=The disease is caused by mutations affecting the gene represented in this entry. Patients affected by the amyelinating form carry a causative, homozygous deletion encompassing a myelin-specific enhancer of EGR2 (PubMed:22522483). {ECO:0000269|PubMed:22522483}.; DISEASE: Charcot-Marie-Tooth disease 1D (CMT1D) [MIM:607678]: A dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot- Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. {ECO:0000269|PubMed:10502832, ECO:0000269|PubMed:10762521, ECO:0000269|PubMed:11239949, ECO:0000269|PubMed:12736090, ECO:0000269|PubMed:15241803, ECO:0000269|PubMed:15947997, ECO:0000269|PubMed:9537424, ECO:0000269|Ref.15}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Dejerine-Sottas syndrome (DSS) [MIM:145900]: A severe degenerating neuropathy of the demyelinating Charcot-Marie-Tooth disease category, with onset by age 2 years. Characterized by motor and sensory neuropathy with very slow nerve conduction velocities, increased cerebrospinal fluid protein concentrations, hypertrophic nerve changes, delayed age of walking as well as areflexia. There are both autosomal dominant and autosomal recessive forms of Dejerine-Sottas syndrome. {ECO:0000269|PubMed:10371530}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
HTLV-I infection - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Hepatitis B - Homo sapiens (human);White fat cell differentiation;Adipogenesis;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;White fat cell differentiation;Transcriptional cascade regulating adipogenesis;Validated transcriptional targets of TAp63 isoforms;Calcineurin-regulated NFAT-dependent transcription in lymphocytes;IL4-mediated signaling events (Consensus)

Recessive Scores

pRec
0.665

Intolerance Scores

loftool
0.233
rvis_EVS
-0.23
rvis_percentile_EVS
37.11

Haploinsufficiency Scores

pHI
0.970
hipred
Y
hipred_score
0.692
ghis
0.538

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.996

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Egr2
Phenotype
hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; vision/eye phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype;

Zebrafish Information Network

Gene name
egr2b
Affected structure
posterior lateral line nerve
Phenotype tag
abnormal
Phenotype quality
absent

Gene ontology

Biological process
regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;protein export from nucleus;brain development;peripheral nervous system development;learning or memory;rhythmic behavior;motor neuron axon guidance;Schwann cell differentiation;protein sumoylation;facial nerve structural organization;rhombomere 3 formation;rhombomere 5 formation;regulation of ossification;response to insulin;brain segmentation;skeletal muscle cell differentiation;myelination;fat cell differentiation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;regulation of neuronal synaptic plasticity;cellular response to organic substance
Cellular component
nucleus;nucleoplasm;cytoplasm;intracellular membrane-bounded organelle
Molecular function
RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II activating transcription factor binding;DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;DNA-binding transcription factor activity;protein binding;transferase activity;ubiquitin protein ligase binding;transcription regulatory region DNA binding;metal ion binding;HMG box domain binding