SMG7

Chr 1

SMG7 nonsense mediated mRNA decay factor

Also known as: C1orf16, EST1C, SGA56M

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]

OMIMResearchGenerating clinical summary…
LOFmechanismLOEUF 0.22
Clinical SummarySMG7
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
125 VUS of 159 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.22LOEUF
pLI 1.000
Z-score 6.60
OE 0.12 (0.070.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.19Z-score
OE missense 0.75 (0.700.81)
466 obs / 619.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.12 (0.070.22)
00.351.4
Missense OE?0.75 (0.700.81)
00.61.4
Synonymous OE?0.96
01.21.6
LoF obs/exp: 8 / 65.8Missense obs/exp: 466 / 619.6Syn Z: 0.53

This gene — mechanism propensity

DN
0.3495th %ile
GOF
0.2696th %ile
LOF
0.75top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.22

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

159 submitted variants in ClinVar

Classification Summary

VUS125
Likely Benign3
125
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
1
124
0
0
125
Likely Benign
0
2
0
1
3
Benign
0
0
0
0
0
Total112601128

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

28 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap SMG7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

SMG7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →