NFE2

nuclear factor, erythroid 2, the group of Basic leucine zipper proteins

Basic information

Region (hg38): 12:54292110-54301015

Links

ENSG00000123405 ∙ NCBI:4778 ∙ OMIM:601490 ∙ HGNC:7780 ∙ Uniprot:Q16621 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NFE2 gene.

• Inborn genetic diseases (9 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NFE2 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				1		1
missense			9			9
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	9	1	0

Variants in NFE2

This is a list of pathogenic ClinVar variants found in the NFE2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-54292400-C-T		not specified	Uncertain significance (May 18, 2022)
12-54292427-C-T		not specified	Uncertain significance (Apr 04, 2023)
12-54292460-A-G		not specified	Uncertain significance (Oct 18, 2021)
12-54292465-C-T		not specified	Uncertain significance (Feb 01, 2023)
12-54292501-T-A		not specified	Uncertain significance (Feb 15, 2023)
12-54292621-A-C		not specified	Uncertain significance (Apr 18, 2023)
12-54292754-C-G		not specified	Uncertain significance (Jun 09, 2022)
12-54292907-G-T		not specified	Uncertain significance (May 09, 2023)
12-54292990-C-T		not specified	Uncertain significance (Mar 14, 2023)
12-54292993-C-T		not specified	Uncertain significance (Feb 14, 2023)
12-54293064-G-A			Likely benign (Feb 01, 2023)
12-54293362-T-C		not specified	Uncertain significance (Dec 18, 2023)
12-54295172-A-G		not specified	Uncertain significance (May 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NFE2	protein_coding	protein_coding	ENST00000540264	2	9011

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.667	0.332	125735	0	8	125743	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.22	176	228	0.772	0.0000146	2352
Missense in Polyphen		55	86.017	0.63941		809
Synonymous	0.327	91	95.1	0.957	0.00000529	831
Loss of Function	2.71	2	12.2	0.163	7.06e-7	142

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000296	0.0000296
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000547	0.0000544
Finnish	0.0000488	0.0000462
European (Non-Finnish)	0.0000101	0.00000879
Middle Eastern	0.0000547	0.0000544
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the NF-E2 complex essential for regulating erythroid and megakaryocytic maturation and differentiation. Binds to the hypersensitive site 2 (HS2) of the beta-globin control region (LCR). This subunit (NFE2) recognizes the TCAT/C sequence of the AP-1-like core palindrome present in a number of erythroid and megakaryocytic gene promoters. Requires MAFK or other small MAF proteins for binding to the NF-E2 motif. May play a role in all aspects of hemoglobin production from globin and heme synthesis to procurement of iron. {ECO:0000269|PubMed:11154691, ECO:0000269|PubMed:16287851}.
• Pathway: Hematopoietic Stem Cell Differentiation;Steatosis AOP;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;Gene expression (Transcription);Generic Transcription Pathway;Factors involved in megakaryocyte development and platelet production;RNA Polymerase II Transcription;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;Hemostasis;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

• pRec: 0.360

Intolerance Scores

• loftool: 0.0570
• rvis_EVS: -0.27
• rvis_percentile_EVS: 33.97

Haploinsufficiency Scores

• pHI: 0.507
• hipred: Y
• hipred_score: 0.598
• ghis: 0.623

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nfe2
• Phenotype: skeleton phenotype; immune system phenotype; neoplasm; hematopoietic 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); 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); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: nfe2
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: low saturation

Gene ontology

• Biological process: nucleosome disassembly;regulation of transcription by RNA polymerase II;multicellular organism development;blood coagulation;hemostasis;blood circulation;regulation of megakaryocyte differentiation;positive regulation of transcription, DNA-templated
• Cellular component: nucleus;nucleoplasm;cytoplasm;PML body;protein-DNA complex
• Molecular function: transcription regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;proximal promoter sequence-specific DNA binding;DNA binding;DNA-binding transcription factor activity;transcription coactivator activity;protein binding;sequence-specific DNA binding;protein N-terminus binding;WW domain binding