NFE2L3

Chr 7

NFE2 like bZIP transcription factor 3

Also known as: NRF3

NCBI Gene: 9603ENSG00000050344UniProt: Q9Y4A8

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]

190
ClinVar variants
31
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NFE2L3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 149 VUS of 190 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.31LOEUF
pLI 0.000
Z-score 0.50
OE 0.88 (0.60–1.31)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-3.75Z-score
OE missense 1.59 (1.48–1.71)
512 obs / 322.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.88 (0.60–1.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.59 (1.48–1.71)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.52
0≤1.21.6
LoF obs/exp: 17 / 19.4Missense obs/exp: 512 / 322.6Syn Z: -4.64

ClinVar Variant Classifications

190 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic4
VUS149
Likely Benign10
27
Pathogenic
4
Likely Pathogenic
149
VUS
10
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
0
4
0
4
VUS
1
140
8
0
149
Likely Benign
0
8
1
1
10
Benign
0
0
0
0
0
Total1148401190

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NFE2L3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
NFE2L3 promotes tumor progression and predicts a poor prognosis of bladder cancer.
Qian J et al.·Carcinogenesis
2022
Identification roles of NFE2L3 in digestive system cancers.
Li F et al.·J Cancer Res Clin Oncol
2024
NFE2L1 and NFE2L3 Complementarily Maintain Basal Proteasome Activity in Cancer Cells through CPEB3-Mediated Translational Repression.
Waku T et al.·Mol Cell Biol
2020
NFE2L3 drives hepatocellular carcinoma cell proliferation by regulating the proteasome-dependent degradation of ISGylated p53.
Ren Y et al.·Cancer Sci
2023
The CNC-family transcription factor NRF3: A crucial therapeutic target for cancer treatment.
Yan L et al.·Biochim Biophys Acta Mol Basis Dis
2025Review
The Nrf Family and Its Cardioprotective Potential: Mechanisms, Functions, and Therapeutic Perspectives.
Cui C et al.·Drug Des Devel Ther
2025Review
Systematic review of genome-wide association studies on susceptibility to endometriosis.
Cardoso JV et al.·Eur J Obstet Gynecol Reprod Biol
2020Meta-analysis
TRP-related gene signatures predict survival and the immune microenvironment in rectal cancer: a comprehensive bioinformatics study.
Wang X et al.·Front Immunol
2025
Regulation and function of the NFE2 transcription factor in hematopoietic and non-hematopoietic cells.
Gasiorek JJ et al.·Cell Mol Life Sci
2015Review
Prognostic Value and Immune Infiltration Analysis of Nuclear Factor Erythroid-2 Family Members in Ovarian Cancer.
Dou R et al.·Biomed Res Int
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools