HELT
protein-codinghelt bHLH transcription factor, the group of Basic helix-loop-helix proteins
Gene summary
Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in several processes, including Notch signaling pathway; 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 suckling behavior. Predicted to be located in chromatin. Predicted to be part of transcription regulator complex. 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 ~2.5 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 HELT variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001300781.2. 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 | 34 | 34 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 34 | 1 | 0 | 35 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001287710.1 | 4 | MANE Select | |
| Ensembl | ENSP00000426033.1 | 4 | MANE Select | |
| RefSeq | NP_001287711.1 | 4 | Standard | |
| Ensembl | ENSP00000343464.4 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of transcription by RNA polymerase II
- blood vessel development
- suckling behavior
- Notch signaling pathway
- central nervous system development
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
- transcription factor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000338875
- Coding exons
- 4
- Length
- 1964
- Individuals with no LoFs
- 125707
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 35
- Defined
- 125742
- p
- 0.000139
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.227 | 199 | 190 | 1.05 | 0.00000856 | 2080 |
| Missense (PolyPhen) | 57 | 63.496 | 0.89769 | 776 | ||
| Synonymous | -1.57 | 105 | 86.4 | 1.22 | 0.00000399 | 700 |
| Loss of Function | 1.18 | 6 | 10.1 | 0.597 | 4.29e-7 | 120 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00047 | 0.00044 | rare |
| Finnish | 0.00033 | 0.00032 | rare |
| European (Non-Finnish) | 0.00012 | 0.00012 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional repressor which binds preferentially to the canonical E box sequence 5'-CACGCG-3'. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.191
Intolerance Scores
- LoFtool
- 0.355
- RVIS EVS
- -0.49
- RVIS percentile EVS
- 22.36
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.862
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |