NFE2L2
NFE2 like bZIP transcription factor 2, the group of Basic leucine zipper proteins|MicroRNA protein coding host genes
Basic information
Region (hg38): 2:177218667-177392756
Links
Phenotypes
GenCC
Source:
- immunodeficiency, developmental delay, and hypohomocysteinemia (Strong), mode of inheritance: AD
- immunodeficiency, developmental delay, and hypohomocysteinemia (Limited), mode of inheritance: AD
- immunodeficiency, developmental delay, and hypohomocysteinemia (Strong), mode of inheritance: AD
- immunodeficiency, developmental delay, and hypohomocysteinemia (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Immunodeficiency, developmental delay, and hypohomocysteinemia | AD | Allergy/Immunology/Infectious; Biochemical | The condition can manifest with immunodeficiency (for which antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial), liver damage, and other features, and medical management (with luteolin and ascorbic acid) has been described as beneficial related to certain parameters, such as liver enzymes and reported frequency of infections | Allergy/Immunology/Infectious; Biochemical; Cardiovascular; Gastrointestinal; Neurologic | 29018201 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (366 variants)
- not_specified (71 variants)
- NFE2L2-related_disorder (17 variants)
- Immunodeficiency,_developmental_delay,_and_hypohomocysteinemia (16 variants)
- Neurodevelopmental_abnormality (1 variants)
- Lung_cancer (1 variants)
- Colorectal_cancer (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NFE2L2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006164.5. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 97 | 3 | 101 | ||
| missense | 3 | 3 | 199 | 26 | 25 | 256 |
| nonsense | 6 | 1 | 7 | |||
| start loss | 1 | 1 | ||||
| frameshift | 11 | 11 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 3 | 3 | 221 | 124 | 28 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NFE2L2 | protein_coding | protein_coding | ENST00000397062 | 5 | 165103 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 124778 | 0 | 14 | 124792 | 0.0000561 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.21 | 252 | 312 | 0.807 | 0.0000155 | 4029 |
| Missense in Polyphen | 39 | 83.019 | 0.46977 | 1101 | ||
| Synonymous | 0.842 | 105 | 117 | 0.901 | 0.00000611 | 1134 |
| Loss of Function | 2.74 | 8 | 21.8 | 0.367 | 0.00000107 | 284 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000125 | 0.000125 |
| Ashkenazi Jewish | 0.0000993 | 0.0000993 |
| East Asian | 0.000168 | 0.000167 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000443 | 0.0000441 |
| Middle Eastern | 0.000168 | 0.000167 |
| South Asian | 0.0000369 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Transcription activator that binds to antioxidant response (ARE) elements in the promoter regions of target genes. Important for the coordinated up-regulation of genes in response to oxidative stress and the regulation of cellular redox conditions. May be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region. {ECO:0000269|PubMed:11035812, ECO:0000269|PubMed:29018201}.;
- Disease
- DISEASE: Immunodeficiency, developmental delay, and hypohomocysteinemia (IMDDHH) [MIM:617744]: An early onset multisystem disorder characterized by immunodeficiency, recurrent infections, developmental delay, poor growth, intellectual disability, and hypohomocysteinemia. Some patients manifest congenital cardiac defects. IMDDHH inheritance pattern is autosomal dominant. {ECO:0000269|PubMed:29018201}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Protein processing in endoplasmic reticulum - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Quercetin and Nf-kB- AP-1 Induced Cell Apoptosis;Aryl Hydrocarbon Receptor;Selenium Metabolism and Selenoproteins;Mesodermal Commitment Pathway;Aryl Hydrocarbon Receptor Pathway;Nuclear Receptors Meta-Pathway;NRF2 pathway;Transcriptional activation by NRF2;Photodynamic therapy-induced AP-1 survival signaling.;Photodynamic therapy-induced NFE2L2 (NRF2) survival signaling;Photodynamic therapy-induced unfolded protein response;Lung fibrosis;Simplified Interaction Map Between LOXL4 and Oxidative Stress Pathway;Oxidative Stress;Hereditary Leiomyomatosis and Renal Cell Carcinoma Pathway;oxidative stress induced gene expression via nrf2
(Consensus)
Recessive Scores
- pRec
- 0.101
Intolerance Scores
- loftool
- 0.199
- rvis_EVS
- 0.04
- rvis_percentile_EVS
- 57.31
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.993
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Zebrafish Information Network
- Gene name
- nfe2l2b
- Affected structure
- anatomical structure
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- transcription by RNA polymerase II;inflammatory response;aging;proteasomal ubiquitin-independent protein catabolic process;positive regulation of gene expression;negative regulation of cardiac muscle cell apoptotic process;positive regulation of neuron projection development;viral process;protein ubiquitination;positive regulation of blood coagulation;endoplasmic reticulum unfolded protein response;cellular response to oxidative stress;positive regulation of transcription from RNA polymerase II promoter in response to stress;positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress;PERK-mediated unfolded protein response;cellular response to glucose starvation;proteasome-mediated ubiquitin-dependent protein catabolic process;positive regulation of blood vessel endothelial cell migration;cell redox homeostasis;positive regulation of angiogenesis;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;regulation of embryonic development;aflatoxin catabolic process;positive regulation of glucose import;positive regulation of transcription from RNA polymerase II promoter in response to hypoxia;cellular response to hydrogen peroxide;cellular response to tumor necrosis factor;cellular response to fluid shear stress;cellular response to laminar fluid shear stress;negative regulation of hematopoietic stem cell differentiation;negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway;positive regulation of ER-associated ubiquitin-dependent protein catabolic process;negative regulation of hydrogen peroxide-induced cell death;positive regulation of glutathione biosynthetic process;cellular response to angiotensin;negative regulation of vascular associated smooth muscle cell migration;regulation of removal of superoxide radicals;negative regulation of endothelial cell apoptotic process;positive regulation of reactive oxygen species metabolic process
- Cellular component
- chromatin;nucleus;nucleoplasm;cytoplasm;Golgi apparatus;centrosome;cytosol;plasma membrane;protein-DNA complex
- Molecular function
- transcription regulatory region sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II activating transcription factor binding;transcription cofactor binding;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;protein domain specific binding;transcription regulatory region DNA binding