MXD4: A Key Regulator of Myc-Mediated Transcription
Comprehensive genomic and functional analysis of the MXD4 gene, a member of the MAD family of basic helix-loop-helix leucine zipper transcription factors.
Gene Information Card
| Symbol | MXD4 |
|---|---|
| Full Name | MAX dimerization protein 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 4p16.3 |
| NCBI Gene ID | 10608 ncbi.nlm.nih.gov/gene/10608 |
| Ensembl ID | ENSG00000138668 |
| UniProt ID | Q14582 |
| OMIM ID | 604786 |
| HGNC ID | 13999 |
| Aliases | MAD4, bHLHc12 |
Description
MXD4 (MAX dimerization protein 4) encodes a member of the MAD family of basic helix-loop-helix leucine zipper (bHLHZip) transcription factors. The encoded protein forms heterodimers with MAX, competing with MYC for MAX binding. MXD4-MAX complexes repress transcription by recruiting corepressor complexes containing histone deacetylases, thereby antagonizing MYC-mediated cell proliferation and promoting differentiation. MXD4 is involved in cell cycle regulation, apoptosis, and tumor suppression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute myeloid leukemia | MXD4 downregulation may relieve MYC repression, contributing to leukemogenesis. | PubMed: 21572415 |
| Breast cancer | Reduced MXD4 expression correlates with poor prognosis and MYC activation. | PubMed: 23382210 |
| Colorectal cancer | MXD4 promoter hypermethylation leads to silencing and MYC pathway activation. | PubMed: 24836962 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Bone marrow | 10.2 | Medium |
| Spleen | 8.9 | Medium |
| Lung | 4.3 | Low |
| Brain | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.8 | High expression |
| MCF7 (breast cancer) | 6.2 | Moderate expression |
| HCT116 (colorectal) | 3.5 | Low expression |
| HEK293 (embryonic kidney) | 1.9 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Likely loss of start codon; predicted loss of function |
| c.256C>T (p.Arg86Trp) | Missense | <0.1% | Located in bHLH domain; may impair DNA binding |
| c.403_404insA (p.Thr135Asnfs*12) | Frameshift | <0.1% | Truncating; loss of leucine zipper domain |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein before or within the leucine zipper domain are predicted to result in loss of function, impairing heterodimerization with MAX and transcriptional repression.
Gain of Function (GOF)
No gain-of-function mutations have been reported for MXD4 in the literature or curated databases.
Dominant Negative (DN)
Mutations in the bHLH domain (e.g., p.Arg86Trp) may produce a protein that binds MAX but fails to repress transcription, potentially acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• MYC-MAX-MAD network (REACT: R-HSA-212294)
• Transcriptional regulation by the bHLH-Zip factors (REACT: R-HSA-9616222)
• HDACs deacetylate histones (REACT: R-HSA-3214815)
Protein Summary
MXD4 (MAD4) is a 221-amino acid protein containing a basic helix-loop-helix leucine zipper domain. It heterodimerizes with MAX and binds to E-box DNA sequences (CACGTG). The MXD4-MAX complex recruits mSin3 and histone deacetylases to repress transcription of MYC target genes. MXD4 is widely expressed in hematopoietic tissues and is implicated in cell cycle arrest, differentiation, and tumor suppression. Its expression is frequently downregulated in cancers, often via promoter methylation or transcriptional silencing.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MXD4 Knockout HEK293 Cell Line | EDJ-KQ50992 | Human | 10608 | Details Get a Quote |
| MXD4 Knockout HeLa Cell Line | EDJ-KQ55442 | Human | 10608 | Details Get a Quote |
| MXD4 Knockout A-549 Cell Line | EDJ-KQ63923 | Human | 10608 | Details Get a Quote |
| MXD4 Knockout HCT 116 Cell Line | EDJ-KQ72381 | Human | 10608 | Details Get a Quote |
