MBD4: Methyl-CpG Binding Domain Protein 4
A DNA glycosylase involved in mismatch repair and tumor suppression
Gene Information Card
| Symbol | MBD4 |
|---|---|
| Full Name | Methyl-CpG Binding Domain Protein 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q21.3 |
| NCBI Gene ID | 8930 ncbi.nlm.nih.gov/gene/8930 |
| Ensembl ID | ENSG00000129071 |
| UniProt ID | O95243 |
| OMIM ID | 603574 |
| HGNC ID | 6919 |
| Aliases | MED1 |
Description
MBD4 (Methyl-CpG Binding Domain Protein 4) encodes a DNA glycosylase that specifically recognizes and repairs mismatched bases at methylated CpG sites. It is involved in the base excision repair (BER) pathway and acts as a tumor suppressor by preventing G:T mismatches arising from spontaneous deamination of 5-methylcytosine. Mutations in MBD4 are associated with microsatellite instability and increased risk of colorectal and endometrial cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Loss-of-function mutations lead to accumulation of C>T transitions at CpG sites, promoting tumorigenesis | COSMIC, ClinVar |
| Endometrial cancer | Somatic frameshift mutations in MBD4 are common in microsatellite-unstable tumors | COSMIC, ClinVar |
| MBD4 deficiency syndrome | Biallelic germline mutations cause a syndrome with multiple adenomatous polyps and early-onset colorectal cancer | OMIM #603574 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Colon | 12.5 | Medium |
| Endometrium | 10.8 | Medium |
| Testis | 8.9 | Low |
| Brain | 6.2 | Low |
| Liver | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.3 | Cervical cancer cell line |
| HCT116 | 18.7 | Colorectal carcinoma cell line |
| MCF7 | 9.2 | Breast cancer cell line |
| A549 | 7.8 | Lung carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.310C>T (p.Arg104*) | Nonsense | 1.2% in colorectal cancer | Loss of function |
| c.1462_1463del (p.Leu488fs) | Frameshift | 0.8% in endometrial cancer | Loss of function |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most MBD4 mutations are loss-of-function, impairing DNA glycosylase activity and leading to increased mutation rate at CpG sites.
Gain of Function (GOF)
No gain-of-function mutations have been reported for MBD4.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for MBD4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Base excision repair (BER) - Reactome R-HSA-73929
• Mismatch repair - Reactome R-HSA-5358565
Protein Summary
MBD4 is a 580-amino acid protein containing an N-terminal methyl-CpG binding domain (MBD) and a C-terminal catalytic glycosylase domain. It binds specifically to methylated CpG dinucleotides and excises thymine or uracil from mismatched G:T or G:U pairs, thereby preventing mutations. The protein interacts with MLH1 and other mismatch repair components, linking BER to MMR pathways. MBD4 is widely expressed, with highest levels in colon and endometrium.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MBD4 Knockout HEK293 Cell Line | EDJ-KQ6402 | Human | 8930 | Details Get a Quote |
| MBD4 Knockout A-549 Cell Line | EDJ-KQ29104 | Human | 8930 | Details Get a Quote |
| MBD4 Knockout HCT 116 Cell Line | EDJ-KQ30428 | Human | 8930 | Details Get a Quote |
| MBD4 Knockout HeLa Cell Line | EDJ-KQ30429 | Human | 8930 | Details Get a Quote |
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