HES3

Chr 1

hes family bHLH transcription factor 3

Also known as: bHLHb43

NCBI Gene: 390992 ENSG00000173673 UniProt: Q5TGS1 OMIM: 609971

The HES3 protein functions as a transcriptional repressor that inhibits genes requiring basic helix-loop-helix (bHLH) proteins for transcription and is predicted to regulate neurogenesis and nervous system development. Currently, no established human diseases have been definitively linked to HES3 mutations in the medical literature. The gene shows relatively low constraint against loss-of-function variants (pLI = 0.28, LOEUF = 1.25), suggesting it may be more tolerant to genetic variation than highly disease-associated genes.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in anterior/posterior pattern specification; negative regulation of transcription by RNA polymerase II; and regulation of neurogenesis. Predicted to act upstream of or within several processes, including nervous system development; positive regulation of transcription by RNA polymerase II; and regulation of timing of neuron differentiation. Predicted to be located in chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

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

1.25

LOEUF

Mechanism· predicted