ZNF654

Chr 3

zinc finger protein 654

NCBI Gene: 55279 ENSG00000175105 UniProt: Q8IZM8

ZNF654 encodes a transcription factor that binds DNA and regulates gene transcription by RNA polymerase II in the nucleus. Mutations cause autosomal dominant intellectual disability with seizures, and the gene is highly constrained against loss-of-function variants (pLI 0.997, LOEUF 0.17), indicating that even single functional copies are critical for normal development.

ResearchSummary from RefSeq, UniProt

Predicted to enable DNA binding activity and DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

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

0.17

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

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