HES3
Chr 1hes family bHLH transcription factor 3
Also known as: bHLHb43
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.
Some data sources returned errors (1)
gnomad: TimeoutError: The operation was aborted due to timeout
Population Genetics & Constraint
Constraint data not available from gnomAD.
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
91 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 53 | 0 | 53 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 27 | 4 | 0 | 31 |
Likely Benign | 0 | 2 | 0 | 0 | 2 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 0 | 29 | 60 | 0 | 89 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
HES3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools