HES3
protein-codinghes family bHLH transcription factor 3, the group of Basic helix-loop-helix proteins
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HES3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001024598.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 27 | 2 | 29 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 28 | 2 | 0 | 30 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001019769.1 | 3 | MANE Select | |
| Ensembl | ENSP00000367130.3 | 3 | MANE Select | |
| Ensembl | ENSP00000516434.1 | 4 | Standard | |
| Ensembl | ENSP00000516434.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| her3 | Danio rerio | Structure: rhombomere 4 Quality: mislocalised abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Human papillomavirus infection - Homo sapiens (human)
Biological Process
- negative regulation of transcription by RNA polymerase II
- in utero embryonic development
- somitogenesis
- Notch signaling pathway
- midbrain-hindbrain boundary morphogenesis
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- transcription corepressor activity
- transcription factor binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000377898
- Coding exons
- 3
- Length
- 1387
- Individuals with no LoFs
- 124744
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 124749
- p
- 0.0000200
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.577 | 68 | 82.8 | 0.821 | 0.00000386 | 1128 |
| Missense (PolyPhen) | 23 | 28.293 | 0.81292 | 338 | ||
| Synonymous | -1.05 | 46 | 37.8 | 1.22 | 0.00000182 | 395 |
| Loss of Function | 1.31 | 1 | 3.72 | 0.269 | 1.55e-7 | 52 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00013 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00017 | 0.00017 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional repressor of genes that require a bHLH protein for their transcription. {ECO:0000250}.;
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.111
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |