BACH1: BTB Domain and CNC Homolog 1 – Heme-Regulated Transcription Factor
A key regulator of oxidative stress, heme homeostasis, and iron metabolism; implicated in cancer, cardiovascular disease, and neurodegenerative disorders.
Gene Information Card
| Symbol | BACH1 |
|---|---|
| Full Name | BTB domain and CNC homolog 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 21q22.11 |
| NCBI Gene ID | 571 ncbi.nlm.nih.gov/gene/571 |
| Ensembl ID | ENSG00000156273 |
| UniProt ID | O14867 |
| OMIM ID | 602751 |
| HGNC ID | 935 |
| Aliases | BTBD24, HEBP1, BACH-1, HA2303 |
Description
BACH1 (BTB domain and CNC homolog 1) encodes a transcription factor that belongs to the basic leucine zipper (bZIP) family. It forms heterodimers with small Maf proteins and binds to Maf recognition elements (MAREs) to repress target genes involved in heme metabolism, oxidative stress response, and iron homeostasis. Under normal conditions, BACH1 represses genes such as HMOX1 (heme oxygenase 1) and FTH1 (ferritin heavy chain). Heme binding induces nuclear export and degradation of BACH1, relieving repression. Dysregulation of BACH1 is associated with various cancers, cardiovascular diseases, and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (breast, lung, prostate, colorectal) | BACH1 overexpression promotes metastasis and chemoresistance; loss of heme regulation leads to sustained repression of antioxidant genes | PMID: 25910212, PMID: 28431213, PMID: 30397376 |
| Cardiovascular disease (atherosclerosis, cardiac hypertrophy) | BACH1 represses antioxidant and anti-inflammatory genes, contributing to endothelial dysfunction and cardiac remodeling | PMID: 23395176, PMID: 27559042 |
| Neurodegenerative disorders (Alzheimer's, Parkinson's) | BACH1-mediated oxidative stress and iron accumulation exacerbate neuronal damage | PMID: 25681666, PMID: 28930670 |
| Hemochromatosis / iron overload | BACH1 regulates hepcidin and ferritin; altered BACH1 activity disrupts iron homeostasis | PMID: 21149635 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Liver | 8.2 | Medium |
| Lung | 6.4 | Low |
| Brain | 4.1 | Low |
| Heart | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression; commonly used for functional studies |
| HeLa | 11.7 | Moderate expression; cervical cancer line |
| MCF7 | 9.3 | Breast cancer; BACH1 implicated in metastasis |
| A549 | 7.8 | Lung cancer; BACH1 regulates oxidative stress |
| K562 | 18.5 | Leukemia; high BACH1 expression linked to heme regulation |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1072C>T (p.Arg358Trp) | Missense | Rare (0.01% in ExAC) | Alters DNA-binding domain; may affect transcriptional repression |
| c.1366G>A (p.Gly456Ser) | Missense | Rare (0.005% in ExAC) | Located in bZIP domain; potential impact on dimerization |
| c.1780_1781insA (p.Thr594Asnfs*2) | Frameshift | Very rare | Truncation; loss of C-terminal regulatory region |
| Amplification (21q22.11) | Copy number gain | Observed in breast and lung cancers (TCGA) | Increased BACH1 expression; associated with poor prognosis |
Mutation functional classification
Loss of Function (LOF)
Frameshift or nonsense mutations that truncate the protein, particularly in the bZIP or BTB domains, impair DNA binding and transcriptional repression.
Gain of Function (GOF)
Amplification or overexpression of wild-type BACH1 leads to sustained repression of antioxidant and heme-related genes, promoting oxidative stress and tumor progression.
Dominant Negative (DN)
Missense mutations in the BTB domain (e.g., p.Arg358Trp) may disrupt dimerization with Maf proteins, interfering with normal BACH1 function.
View complete mutation data：
Gene Ontology (GO)
| • RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978) | • DNA-binding transcription factor activity (GO:0000981) |
| • transcription corepressor activity (GO:0003714) | • nucleus (GO:0005634) |
| • cytoplasm (GO:0005737) | • cytosol (GO:0005829) |
| • identical protein binding (GO:0042802) | • protein heterodimerization activity (GO:0046982) |
| • metal ion binding (GO:0046872) | • negative regulation of heme oxygenase (decyclizing) activity (GO:1904600) |
Pathways
• Heme signaling pathway (Reactome: R-HSA-917937)
• Oxidative stress response (Reactome: R-HSA-3371497)
• Iron metabolism and homeostasis (KEGG: hsa04978)
• Nrf2 pathway (KEGG: hsa05208)
• p53 signaling pathway (Reactome: R-HSA-3700989)
Protein Summary
BACH1 is a 739-amino acid transcription factor containing an N-terminal BTB/POZ domain, a central bZIP domain, and a C-terminal heme-binding region. It forms heterodimers with small Maf proteins and binds to MAREs to repress target genes. Heme binding triggers nuclear export and ubiquitin-mediated degradation, allowing derepression of genes such as HMOX1 and FTH1. BACH1 plays a critical role in cellular adaptation to oxidative stress, iron metabolism, and inflammation. Dysregulation contributes to cancer progression, cardiovascular pathology, and neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BACH1 Knockout HEK293 Cell Line | EDJ-KQ2927 | Human | 571 | Details Get a Quote |
| BACH1 Knockout A-549 Cell Line | EDJ-KQ24031 | Human | 571 | Details Get a Quote |
| BACH1 Knockout HCT 116 Cell Line | EDJ-KQ24032 | Human | 571 | Details Get a Quote |
| BACH1 Knockout HeLa Cell Line | EDJ-KQ24033 | Human | 571 | Details Get a Quote |
