BHLHA15
protein-codingbasic helix-loop-helix family member a15, the group of Basic helix-loop-helix proteins
Gene summary
Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in several processes, including cellular response to glucose starvation; endoplasmic reticulum unfolded protein response; and negative regulation of myotube differentiation. Predicted to act upstream of or within several processes, including cell-cell adhesion mediated by cadherin; intracellular distribution of mitochondria; and mitochondrial calcium ion transmembrane transport. Predicted to be located in chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jun 2026]
- BHLHB8
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.0 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 BHLHA15 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_177455.4. 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 | 0 | |||||
| missense | 40 | 2 | 42 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 40 | 2 | 0 | 42 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_803238.1 | 1 | MANE Select | |
| Ensembl | ENSP00000476312.1 | 1 | MANE Select | |
| Ensembl | ENSP00000326391.2 | 1 | Standard | |
| Ensembl | ENSP00000600596.1 | 1 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| bhlha15 | Danio rerio | Structure: exocrine pancreas Quality: disorganized abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Maturity onset diabetes of the young - Homo sapiens (human)
Biological Process
- mitochondrial calcium ion transmembrane transport
- Golgi organization
- G protein-coupled receptor signaling pathway
- cell-cell signaling
- negative regulation of myotube differentiation
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
- protein homodimerization activity
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000609256
- Coding exons
- 1
- Length
- 1553
- Individuals with no LoFs
- 119150
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 119155
- p
- 0.0000210
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.490 | 96 | 110 | 0.869 | 0.00000833 | 1169 |
| Missense (PolyPhen) | 42 | 58.295 | 0.72047 | 537 | ||
| Synonymous | -0.652 | 59 | 53.0 | 1.11 | 0.00000404 | 426 |
| Loss of Function | 0.0180 | 3 | 3.03 | 0.989 | 1.29e-7 | 42 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000051 | 0.000049 | rare |
| European (Non-Finnish) | 0.000042 | 0.000037 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in controlling the transcriptional activity of MYOD1, ensuring that expanding myoblast populations remain undifferentiated. Repression may occur through muscle-specific E- box occupancy by homodimers. May also negatively regulate bHLH- mediated transcription through an N-terminal repressor domain. Serves as a key regulator of acinar cell function, stability, and identity. Also required for normal organelle localization in exocrine cells and for mitochondrial calcium ion transport. May function as a unique regulator of gene expression in several different embryonic and postnatal cell lineages. Binds to the E- box consensus sequence 5'-CANNTG-3' (By similarity). {ECO:0000250|UniProtKB:Q9QYC3}.;
Recessive Scores
- pRec
- 0.150
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.441
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |