NFE2L1

NFE2 like bZIP transcription factor 1, the group of Basic leucine zipper proteins

Basic information

Region (hg38): 17:48048328-48061545

Previous symbols: [ "TCF11" ]

Links

ENSG00000082641 ∙ NCBI:4779 ∙ OMIM:163260 ∙ HGNC:7781 ∙ Uniprot:Q14494 ∙ 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 NFE2L1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NFE2L1 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			42	1		43
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	43	1	1

Variants in NFE2L1

This is a list of pathogenic ClinVar variants found in the NFE2L1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-48051155-C-T		not specified	Uncertain significance (Jun 29, 2022)
17-48051227-C-T		not specified	Uncertain significance (Jan 03, 2024)
17-48051228-C-T		not specified	Uncertain significance (Nov 23, 2021)
17-48051265-C-T			Benign (Jul 13, 2018)
17-48051304-G-T		not specified	Uncertain significance (Jun 07, 2024)
17-48051315-G-T		not specified	Uncertain significance (Jun 07, 2023)
17-48051359-C-T		not specified	Uncertain significance (Oct 12, 2021)
17-48051360-G-A		not specified	Uncertain significance (Dec 27, 2023)
17-48051362-C-T		not specified	Uncertain significance (Feb 02, 2022)
17-48051536-G-C		not specified	Uncertain significance (Jan 23, 2023)
17-48051537-T-C		not specified	Uncertain significance (Dec 17, 2023)
17-48051539-C-T			Uncertain significance (Jul 14, 2022)
17-48056440-C-T		not specified	Uncertain significance (Jun 01, 2023)
17-48056456-A-G		not specified	Uncertain significance (Jun 11, 2021)
17-48056464-C-T		not specified	Uncertain significance (Oct 22, 2021)
17-48056465-G-A		not specified	Uncertain significance (Apr 28, 2023)
17-48056498-G-A		not specified	Likely benign (Jun 02, 2023)
17-48056507-G-A		not specified	Uncertain significance (Mar 02, 2023)
17-48056509-G-A		not specified	Uncertain significance (Nov 30, 2022)
17-48056524-G-T		not specified	Uncertain significance (Nov 10, 2022)
17-48056536-G-A		not specified	Uncertain significance (Jul 26, 2022)
17-48056575-A-T		not specified	Uncertain significance (Oct 29, 2021)
17-48057075-G-T		not specified	Uncertain significance (Apr 08, 2022)
17-48057078-T-G		not specified	Uncertain significance (Dec 14, 2022)
17-48057337-G-A			Likely benign (Jul 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NFE2L1	protein_coding	protein_coding	ENST00000362042	5	13159

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00241	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.76	343	447	0.766	0.0000271	5026
Missense in Polyphen		100	175.06	0.57125		1946
Synonymous	-0.116	192	190	1.01	0.0000112	1624
Loss of Function	4.65	3	30.9	0.0971	0.00000217	283

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000619	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Endoplasmic reticulum membrane sensor NFE2L1: Endoplasmic reticulum membrane sensor that translocates into the nucleus in response to various stresses to act as a transcription factor (PubMed:20932482, PubMed:24448410). Constitutes a precursor of the transcription factor NRF1 (By similarity). Able to detect various cellular stresses, such as cholesterol excess, oxidative stress or proteasome inhibition (PubMed:20932482). In response to stress, it is released from the endoplasmic reticulum membrane following cleavage by the protease DDI2 and translocates into the nucleus to form the transcription factor NRF1 (By similarity). Acts as a key sensor of cholesterol excess: in excess cholesterol conditions, the endoplasmic reticulum membrane form of the protein directly binds cholesterol via its CRAC motif, preventing cleavage and release of the transcription factor NRF1, thereby allowing expression of genes promoting cholesterol removal, such as CD36 (By similarity). Involved in proteasome homeostasis: in response to proteasome inhibition, it is released from the endoplasmic reticulum membrane, translocates to the nucleus and activates expression of genes encoding proteasome subunits (PubMed:20932482). {ECO:0000250|UniProtKB:Q61985, ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:24448410}.

Recessive Scores

• pRec: 0.160

Intolerance Scores

• loftool: 0.105
• rvis_EVS: -1.46
• rvis_percentile_EVS: 3.78

Haploinsufficiency Scores

• pHI: 0.735
• hipred: Y
• hipred_score: 0.775
• ghis: 0.621

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.969

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nfe2l1
• Phenotype: immune system phenotype; liver/biliary system phenotype; embryo phenotype; neoplasm; hematopoietic system phenotype; 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); 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); homeostasis/metabolism phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: nfe2l1b
• Affected structure: anatomical structure
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: transcription by RNA polymerase II;heme biosynthetic process;inflammatory response;cholesterol metabolic process;anatomical structure morphogenesis;erythrocyte differentiation;cellular response to oxidative stress;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus;cytoplasm;endoplasmic reticulum membrane;cytosol;integral component of membrane;protein-containing 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;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;transcription coregulator activity;protein binding;lipid binding;protein domain specific binding;protein-containing complex binding