SMG6

Chr 17

SMG6 nonsense mediated mRNA decay factor

Also known as: C17orf31, EST1A, SMG-6, hEST1A, hSMG5/7a

NCBI Gene: 23293ENSG00000070366UniProt: Q86US8OMIM: 610963

The encoded protein functions as a component of the telomerase ribonucleoprotein complex essential for chromosome end replication and maintenance, and provides endonuclease activity in the nonsense-mediated mRNA decay pathway. Mutations cause autosomal recessive intellectual developmental disorder with cardiac arrhythmias, dysmorphism, and skeletal malformations. This gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.30), indicating intolerance to protein-truncating mutations.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.30
Clinical Summary— SMG6
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
68 unique Pathogenic / Likely Pathogenic· 255 VUS of 368 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.982
Z-score 6.10
OE 0.18 (0.12–0.30)
Highly constrained

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

Missense Constraint
0.18Z-score
OE missense 0.98 (0.93–1.04)
820 obs / 834.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.18 (0.12–0.30)
0≤0.351.4
Missense OE0.98 (0.93–1.04)
0≤0.61.4
Synonymous OE1.16
0≤1.21.6
LoF obs/exp: 12 / 65.1Missense obs/exp: 820 / 834.5Syn Z: -2.28
DN
0.2898th %ile
GOF
0.2597th %ile
LOF
0.74top 10%

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

LOFprediction above median · LOEUF 0.30

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

368 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic62
Likely Pathogenic6
VUS255
Likely Benign17
Benign6
62
Pathogenic
6
Likely Pathogenic
255
VUS
17
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
62
0
62
Likely Pathogenic
0
0
6
0
6
VUS
1
236
17
1
255
Likely Benign
0
10
2
5
17
Benign
0
4
1
1
6
Total1250887346

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

View in ClinVar →

Protein Context — Lollipop Plot

SMG6 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients