EGR2

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

Basic information

Region (hg38): 10:62811996-62819167

Previous symbols: [ "KROX20" ]

Links

ENSG00000122877 ∙ NCBI:1959 ∙ OMIM:129010 ∙ HGNC:3239 ∙ Uniprot:P11161 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Charcot-Marie-Tooth disease, demyelinating, type 1D; Neuropathy, congenital hypomyelinating, 1, autosomal recessive; Dejerine-Sottas disease	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	9537424; 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	1	99
missense	11	4	194	2		211
nonsense			3			3
start loss						0
frameshift			5			5
inframe indel			13			13
splice donor/acceptor (+/-2bp)						0
splice region				3		3
non coding			14	12	10	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)
10-62812179-T-C		Charcot-Marie-Tooth disease, type I	Uncertain significance (Jun 14, 2016)
10-62812288-C-G		Charcot-Marie-Tooth disease type 1D	Uncertain significance (Jan 13, 2018)
10-62812333-T-C		Charcot-Marie-Tooth disease type 1D	Benign (Jan 13, 2018)
10-62812390-GAGA-G		Charcot-Marie-Tooth disease, type I	Uncertain significance (Jun 14, 2016)
10-62812552-C-T		Charcot-Marie-Tooth disease type 1D	Uncertain significance (Jan 13, 2018)
10-62812561-G-A		Charcot-Marie-Tooth disease type 1D	Uncertain significance (Jan 12, 2018)
10-62812589-A-G		Charcot-Marie-Tooth disease type 1D	Uncertain significance (Jan 13, 2018)
10-62812751-C-T		Charcot-Marie-Tooth disease type 1D	Uncertain significance (Jan 13, 2018)
10-62812778-C-T		Charcot-Marie-Tooth disease type 1D	Benign (Jan 12, 2018)
10-62812919-C-T		Charcot-Marie-Tooth disease type 1D	Benign/Likely benign (Jun 19, 2018)
10-62812920-A-T		Charcot-Marie-Tooth disease type 1D	Benign (Jun 16, 2018)
10-62812977-C-A		Charcot-Marie-Tooth disease type 1D	Uncertain significance (Jan 15, 2018)
10-62813057-T-C		Charcot-Marie-Tooth disease type 1D	Uncertain significance (Jan 13, 2018)
10-62813062-A-T		Charcot-Marie-Tooth disease type 1D	Uncertain significance (Jan 13, 2018)
10-62813128-G-T		Charcot-Marie-Tooth disease type 1D	Uncertain significance (Jan 13, 2018)
10-62813187-GTAT-G			Likely benign (Jan 25, 2018)
10-62813208-C-G		Charcot-Marie-Tooth disease, type I	Uncertain significance (Apr 26, 2023)
10-62813210-A-T		Charcot-Marie-Tooth disease, type I	Likely benign (Oct 07, 2022)
10-62813213-T-G		Charcot-Marie-Tooth disease, type I	Likely benign (Mar 26, 2022)
10-62813217-C-T		Charcot-Marie-Tooth disease, type I	Uncertain significance (Jan 17, 2024)
10-62813218-G-A		Charcot-Marie-Tooth disease, type I	Uncertain significance (Dec 02, 2021)
10-62813220-G-A		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
10-62813224-G-C		Charcot-Marie-Tooth disease, type I	Uncertain significance (Apr 20, 2020)
10-62813224-G-T		Charcot-Marie-Tooth disease, type I	Likely benign (Dec 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EGR2	protein_coding	protein_coding	ENST00000242480	2	107905

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.503	0.493	125744	0	4	125748	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.44	175	293	0.598	0.0000187	3049
Missense in Polyphen		28	62.834	0.44562		668
Synonymous	-0.584	131	123	1.07	0.00000797	1085
Loss of Function	2.42	2	10.4	0.192	6.37e-7	122

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000353	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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