NFIL3

Chr 9

nuclear factor, interleukin 3 regulated

Also known as: E4BP4, IL3BP1, NF-IL3A, NFIL3A

The encoded protein is a transcriptional regulator that binds to activating transcription factor (ATF) sites in cellular and viral promoters and negatively regulates circadian rhythm by repressing PER1 and PER2 expression. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, developmental delay, and seizures, with some patients showing sleep disturbances consistent with the gene's role in circadian regulation. The gene is highly constrained against loss-of-function variants (pLI 0.82, LOEUF 0.44), indicating that such variants are likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.44
Clinical SummaryNFIL3
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.44LOEUF
pLI 0.820
Z-score 3.03
OE 0.14 (0.060.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.60Z-score
OE missense 0.71 (0.630.81)
172 obs / 242.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.14 (0.060.44)
00.351.4
Missense OE0.71 (0.630.81)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 2 / 14.4Missense obs/exp: 172 / 242.2Syn Z: 0.01
DN
0.4090th %ile
GOF
0.1799th %ile
LOF
0.77top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.44

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NFIL3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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