NFE2L3

protein-coding

NFE2 like bZIP transcription factor 3, the group of Basic leucine zipper proteins

Gene summary

This gene encodes a member of the cap 'n' collar basic-region leucine zipper family of transcription factors. The encoded protein heterodimerizes with small musculoaponeurotic fibrosarcoma factors to bind antioxidant response elements in target genes. This protein is a membrane bound glycoprotein that is targeted to the endoplasmic reticulum and the nuclear envelope. Pseudogenes of this gene are found on chromosomes 16, 17, and 18. [provided by RefSeq, Mar 2009]

MANE transcript

NM_004289.7

Inheritance

—

ClinVar variants

U:148B:10

Top phenotype

NFE2L3-related condition

gnomAD constraint

pLI —, LoF o/e 0.88

Max pathogenic AF

—

Genomic locus

chr7:26,152,198-26,187,137

External References & Databases

Ensembl (ENSG00000050344)

Transcript & Mutation Effects

hg38 • Region Span ~34.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NFE2L3 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 144

not providedTotal: 5

NFE2L3-related conditionTotal: 2

Neurodevelopmental disorderTotal: 2

KeratoconusTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004289.7. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	2 clinvar		5
missense			142 clinvar	8 clinvar		150
nonsense						0
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	148	10	0	158

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004289.7	RefSeq	NP_004280.5	4	MANE Select
ENST00000056233.4	Ensembl	ENSP00000056233.3	4	MANE Select
ENST00000607375.1	Ensembl	ENSP00000475463.1	2	Standard
ENST00000927666.1	Ensembl	ENSP00000597725.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
transcription by RNA polymerase II
positive regulation of transcription, DNA-templated

Molecular Function

transcription regulatory region sequence-specific DNA binding
RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
DNA-binding transcription factor activity

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000056233
Coding exons: 4
Length: 34886
Individuals with no LoFs: 125471
Homozygous LoFs: 1
Heterozygous LoFs: 276
Defined: 125748
p: 0.00110

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-3.75	512	323	1.59	0.0000157	4508
Missense (PolyPhen)		102	62.167	1.6407		909
Synonymous	-4.64	195	128	1.52	0.00000640	1380
Loss of Function	0.504	17	19.4	0.876	9.23e-7	270

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0014	0.0014	notable
Latino/Admixed American	0.00081	0.00078	rare
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0.0032	0.0032	notable
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00076	0.00076	rare
South Asian	0.0021	0.0021	notable
Other	0.0021	0.0021	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Activates erythroid-specific, globin gene expression.;

Recessive Scores

pRec: 0.0952

Intolerance Scores

LoFtool: 0.630
RVIS EVS: 0.2
RVIS percentile EVS: 67.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.534

Gene Damage Prediction

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