SMG8: A Key Regulator of Nonsense-Mediated mRNA Decay
Comprehensive gene card for SMG8, including genomic context, expression, mutations, and disease associations.
Gene Information Card
| Symbol | SMG8 |
|---|---|
| Full Name | SMG8, nonsense mediated mRNA decay factor |
| Gene Type | protein-coding |
| Chromosomal Location | 17q22 |
| NCBI Gene ID | 55181 ncbi.nlm.nih.gov/gene/55181 |
| Ensembl ID | ENSG00000108848 |
| UniProt ID | Q8ND04 |
| OMIM ID | 613175 |
| HGNC ID | 25551 |
| Aliases | FLJ10534, MGC138290, MGC138291 |
Description
SMG8 encodes a component of the SMG1-8-9 complex, which is essential for nonsense-mediated mRNA decay (NMD). NMD is a surveillance pathway that degrades mRNAs containing premature termination codons, preventing the production of truncated and potentially harmful proteins. SMG8 regulates the kinase activity of SMG1 and is involved in telomere maintenance and DNA damage response.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | SMG8 mutations may impair NMD, leading to accumulation of aberrant transcripts and promoting tumorigenesis. | COSMIC database reports somatic mutations in multiple cancer types. |
| Primary microcephaly | Biallelic loss-of-function variants in SMG8 have been associated with microcephaly and intellectual disability. | ClinVar and literature (PMID: 31064749) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 14.2 | Medium |
| Brain | 8.5 | Low |
| Liver | 6.1 | Low |
| Kidney | 5.3 | Low |
| Heart | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 12.1 | Cervical carcinoma cell line |
| HEK293 | 10.5 | Embryonic kidney cells |
| K562 | 9.3 | Leukemia cell line |
| A549 | 8.7 | Lung carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1003C>T (p.Arg335*) | Nonsense | Rare | Loss of function; triggers NMD of SMG8 mRNA itself |
| c.1462G>A (p.Glu488Lys) | Missense | 0.01% (gnomAD) | Unknown; may affect protein stability |
| c.1741_1742del (p.Leu581Valfs*2) | Frameshift | Somatic (COSMIC) | Loss of function; observed in colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or trigger NMD, reducing SMG8 levels and impairing NMD efficiency.
Gain of Function (GOF)
No known gain-of-function mutations reported.
Dominant Negative (DN)
Not described; SMG8 functions as part of a complex, and dominant-negative effects are theoretically possible but unconfirmed.
View complete mutation data：
Gene Ontology (GO)
| • nonsense-mediated mRNA decay (GO:0000184) | • protein kinase binding (GO:0019901) |
| • cytoplasm (GO:0005737) | • SMG1-8-9 complex (GO:1990726) |
| • telomere maintenance (GO:0000723) |
Pathways
• Nonsense-Mediated Decay (NMD) - Reactome R-HSA-927802
• SMG1-8-9 complex signaling
Protein Summary
SMG8 is a 991-amino acid protein that forms a stable complex with SMG1 and SMG9. It negatively regulates SMG1 kinase activity, ensuring proper NMD activation. The protein contains a conserved N-terminal domain and is localized predominantly in the cytoplasm. SMG8 also interacts with telomeric proteins and may have roles beyond NMD.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SMG8 Knockout HEK293 Cell Line | EDJ-KQ15366 | Human | 55181 | Details Get a Quote |
| SMG8 Knockout HCT 116 Cell Line | EDJ-KQ46108 | Human | 55181 | Details Get a Quote |
| SMG8 Knockout HeLa Cell Line | EDJ-KQ46109 | Human | 55181 | Details Get a Quote |
| SMG8 Knockout A-549 Cell Line | EDJ-KQ44876 | Human | 55181 | Details Get a Quote |
