SMG6: Telomerase-Binding Protein and Nonsense-Mediated Decay Factor
A dual-function gene involved in telomere maintenance and mRNA surveillance
Gene Information Card
| Symbol | SMG6 |
|---|---|
| Full Name | SMG6 nonsense mediated mRNA decay factor |
| Gene Type | Protein coding |
| Chromosomal Location | 17p13.3 |
| NCBI Gene ID | 23293 ncbi.nlm.nih.gov/gene/23293 |
| Ensembl ID | ENSG00000170370 |
| UniProt ID | Q86US8 |
| OMIM ID | 610963 |
| HGNC ID | 11123 |
| Aliases | EST1A, C17orf31, hEST1A, SMG-6 |
Description
SMG6 (nonsense mediated mRNA decay factor) encodes a protein that functions both in telomere maintenance as a component of the telomerase complex and in nonsense-mediated mRNA decay (NMD) as an endonuclease that cleaves mRNAs containing premature termination codons. The protein localizes to telomeres and is required for telomerase recruitment and telomere elongation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dyskeratosis congenita | Impaired telomere maintenance due to SMG6 mutations | ClinVar |
| Idiopathic pulmonary fibrosis | Telomere dysfunction from SMG6 variants | ClinVar |
| Hepatocellular carcinoma | SMG6 overexpression linked to telomerase activation | COSMIC |
| Breast cancer | SMG6 amplification and altered NMD | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 25.3 | Medium |
| Bone marrow | 18.7 | Medium |
| Lymph node | 15.2 | Medium |
| Brain | 12.1 | Medium |
| Liver | 10.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 22.4 | Embryonic kidney |
| HeLa | 19.8 | Cervical carcinoma |
| K562 | 17.3 | Leukemia |
| MCF7 | 15.6 | Breast cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.01% | Loss of function, NMD defect |
| c.567_568del (p.Glu190fs) | Frameshift | <0.01% | Loss of function, telomere shortening |
| c.2345A>G (p.Asn782Ser) | Missense | 0.02% | Reduced telomerase binding |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in SMG6 impair both NMD and telomere maintenance, leading to telomere shortening and cellular senescence.
Gain of Function (GOF)
Amplification or overexpression of SMG6 in cancers may enhance telomerase activity and promote immortalization.
Dominant Negative (DN)
Not reported for SMG6.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Nonsense-mediated mRNA decay (NMD) pathway
• Telomere maintenance via telomerase
Protein Summary
SMG6 is a 1,419-amino acid protein containing an N-terminal telomerase-binding domain and a C-terminal PIN domain with endonuclease activity. It is essential for the recruitment of telomerase to telomeres and for the cleavage of aberrant mRNAs during NMD. The protein interacts with telomerase RNA component (TERC) and SMG1 kinase.
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