N4BP1

Chr 16

NEDD4 binding protein 1

NCBI Gene: 9683 ENSG00000102921 UniProt: O75113 OMIM: 619138

The protein functions as a negative regulator of innate immune signaling and inflammation, suppressing cytokine production through TRIF-independent Toll-like receptor pathways, and also acts as an RNA nuclease that restricts viral replication by degrading viral mRNAs. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, primarily affecting the nervous system with seizures and developmental delays typically manifesting in infancy. The gene shows high constraint against loss-of-function variants (LOEUF 0.404), indicating that complete loss of protein function is likely not well tolerated.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA nuclease activity; mRNA binding activity; and ubiquitin binding activity. Involved in cellular response to UV and negative regulation of viral genome replication. Predicted to be located in cytosol and nucleolus. Predicted to be active in PML body. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

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.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.40

LOEUF

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Mechanism