SMG7
protein-codingSMG7 nonsense mediated mRNA decay factor
Gene summary
This gene encodes a protein that is essential for nonsense-mediated mRNA decay (NMD); a process whereby transcripts with premature termination codons are targeted for rapid degradation by a mRNA decay complex. The mRNA decay complex consists, in part, of this protein along with proteins SMG5 and UPF1. The N-terminal domain of this protein is thought to mediate its association with SMG5 or UPF1 while the C-terminal domain interacts with the mRNA decay complex. This protein may therefore couple changes in UPF1 phosphorylation state to the degradation of NMD-candidate transcripts. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2011]
- C1orf16
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~126.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0007179
Submitter: Illumina
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SMG7 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001375584.1. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 1 | 4 | |||
| missense | 120 | 1 | 121 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 127 | 2 | 0 | 129 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001362513.1 | 23 | MANE Select | |
| Ensembl | ENSP00000510175.1 | 23 | MANE Select | |
| RefSeq | NP_001167532.1 | 21 | Standard | |
| RefSeq | NP_001317936.1 | 23 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| smg7 | Danio rerio | Structure: post-vent region Quality: bent abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- mRNA surveillance pathway - Homo sapiens (human)
Biological Process
- nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
- mRNA export from nucleus
- telomere maintenance via telomerase
- regulation of telomere maintenance via telomerase
- regulation of dephosphorylation
Molecular Function
- protein binding
- telomeric DNA binding
- protein phosphatase 2A binding
- telomerase RNA binding
Cellular Component
- nucleus
- telomerase holoenzyme complex
- cytoplasm
- cytosol
- intermediate filament cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000507469
- Coding exons
- 23
- Length
- 126031
- Individuals with no LoFs
- 125720
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 19
- Defined
- 125739
- p
- 0.0000756
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.19 | 466 | 620 | 0.752 | 0.0000314 | 7684 |
| Missense (PolyPhen) | 122 | 235.28 | 0.51852 | 2977 | ||
| Synonymous | 0.531 | 224 | 234 | 0.956 | 0.0000123 | 2306 |
| Loss of Function | 6.60 | 8 | 65.8 | 0.122 | 0.00000367 | 700 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000069 | 0.000062 | rare |
| Latino/Admixed American | 0.000040 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000074 | 0.000054 | rare |
| Finnish | 0.00020 | 0.00018 | rare |
| European (Non-Finnish) | 0.00010 | 0.000097 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in nonsense-mediated mRNA decay. Recruits UPF1 to cytoplasmic mRNA decay bodies. Together with SMG5 is thought to provide a link to the mRNA degradation machinery involving exonucleolytic pathways, and to serve as an adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation. {ECO:0000269|PubMed:15546618, ECO:0000269|PubMed:15721257}.;
Recessive Scores
- pRec
- 0.114
Intolerance Scores
- LoFtool
- 0.413
- RVIS EVS
- -0.31
- RVIS percentile EVS
- 32.23
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.885
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |