ZNF598

Chr 16

zinc finger protein 598, E3 ubiquitin ligase

Also known as: HEL2

NCBI Gene: 90850 ENSG00000167962 UniProt: Q86UK7 OMIM: 617508

ZNF598 encodes an E3 ubiquitin ligase that functions as a ribosome collision sensor, detecting stalled ribosomes during translation and triggering ribosome quality control pathways that lead to degradation of aberrant nascent peptides. Mutations cause autosomal recessive neurodevelopmental disorder with or without anomalies of the brain, eye, or heart, typically presenting in early childhood with developmental delay, intellectual disability, and variable congenital malformations. The gene shows high constraint against loss-of-function variants (LOEUF 0.399), indicating that complete loss of protein function is likely not tolerated.

OMIM ResearchSummary from RefSeq, UniProt

Zinc-finger proteins bind nucleic acids and play important roles in various cellular functions, including cell proliferation, differentiation, and apoptosis. This protein and Grb10-interacting GYF protein 2 have been identified as a components of the mammalian 4EHP (m4EHP) complex. The complex is thought to function as a translation repressor in embryonic development. [provided by RefSeq, Oct 2012]

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