SMUG1 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the SMUG1 gene, encoding single-strand-selective monofunctional uracil-DNA glycosylase 1, its role in DNA repair, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | SMUG1 |
|---|---|
| Full Name | Single-strand-selective monofunctional uracil-DNA glycosylase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q13.13 |
| NCBI Gene ID | 23583 ncbi.nlm.nih.gov/gene/23583 |
| Ensembl ID | ENSG00000123415 |
| UniProt ID | Q86U38 |
| OMIM ID | 607753 |
| HGNC ID | 11163 |
| Aliases | FDG, UNG3 |
Description
The SMUG1 gene encodes a DNA glycosylase involved in base excision repair (BER). It specifically recognizes and removes uracil and certain oxidized pyrimidines from DNA, particularly in single-stranded regions. SMUG1 plays a crucial role in maintaining genomic stability by preventing mutagenesis from deaminated cytosine and misincorporated uracil. It is widely expressed and localizes to the nucleus and mitochondria.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | SMUG1 deficiency may lead to increased uracil accumulation and DNA damage, promoting tumorigenesis. Altered expression has been observed in tumors. | COSMIC, literature |
| Lung cancer | Overexpression of SMUG1 in some lung cancers may contribute to resistance to chemotherapeutic agents that induce DNA damage. | COSMIC, literature |
| Breast cancer | Polymorphisms in SMUG1 have been associated with altered DNA repair capacity and increased risk of breast cancer. | ClinVar, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.4 | Medium |
| Kidney | 8.7 | Low |
| Liver | 7.2 | Low |
| Brain | 5.1 | Low |
| Heart | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.5 | Cervical cancer cell line; high expression |
| A549 | 8.2 | Lung carcinoma; moderate expression |
| MCF7 | 7.8 | Breast cancer; moderate expression |
| K562 | 6.1 | Leukemia; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | Rare | Potential loss of start codon, affecting protein translation |
| c.335C>T (p.Pro112Leu) | Missense | 0.01% | May affect enzyme activity or stability |
| c.560G>A (p.Arg187Gln) | Missense | 0.02% | Located in catalytic domain, may reduce uracil glycosylase activity |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair SMUG1 catalytic activity or protein stability lead to reduced uracil excision, increasing mutagenesis and genomic instability.
Gain of Function (GOF)
No known gain-of-function mutations reported; overexpression in some cancers may be considered a gain-of-function at expression level.
Dominant Negative (DN)
No evidence of dominant-negative effects; SMUG1 functions as a monomer, and heterozygous mutations are unlikely to exert dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • uracil DNA N-glycosylase activity |
| • hydrolase activity | • base-excision repair |
| • DNA repair | • nucleus |
| • mitochondrion |
Pathways
• Base excision repair
• DNA damage response
Protein Summary
SMUG1 is a 270-amino acid protein with a conserved catalytic domain. It removes uracil from DNA, especially in single-stranded regions, and also processes 5-hydroxymethyluracil and other oxidized pyrimidines. It initiates BER by creating an abasic site, which is then processed by AP endonucleases. SMUG1 is essential for maintaining genomic integrity in both nuclear and mitochondrial DNA.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SMUG1 Knockout HEK293 Cell Line | EDJ-KQ8077 | Human | 23583 | Details Get a Quote |
| SMUG1 Knockout A-549 Cell Line | EDJ-KQ33908 | Human | 23583 | Details Get a Quote |
| SMUG1 Knockout HCT 116 Cell Line | EDJ-KQ33909 | Human | 23583 | Details Get a Quote |
| SMUG1 Knockout HeLa Cell Line | EDJ-KQ33910 | Human | 23583 | Details Get a Quote |
