NFE2

Chr 12

nuclear factor, erythroid 2

Also known as: NF-E2, p45

NCBI Gene: 4778ENSG00000123405UniProt: Q16621

Enables WW domain binding activity; identical protein binding activity; and sequence-specific double-stranded DNA binding activity. Contributes to cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including labyrinthine layer blood vessel development; negative regulation of bone mineralization; and positive regulation of peptidyl-lysine acetylation. Part of RNA polymerase II transcription regulator complex and protein-DNA complex. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)
thrombocytopenia · ARLimitednot for standalone diagnostic reporting
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
75
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.52
LOEUF
—
Mechanism
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.52LOEUF
pLI 0.667
Z-score 2.71
OE 0.16 (0.07–0.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.22Z-score
OE missense 0.77 (0.68–0.88)
176 obs / 227.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.16 (0.07–0.52)
0≤0.351.4
Missense OE?0.77 (0.68–0.88)
0≤0.61.4
Synonymous OE?0.96
0≤1.21.6
LoF obs/exp: 2 / 12.2Missense obs/exp: 176 / 227.9Syn Z: 0.33

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

NFE2 · protein map & ClinVar variants

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

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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients