SMG1
Chr 16SMG1 nonsense mediated mRNA decay associated PI3K related kinase
Also known as: 61E3.4, ATX, LIP
This gene encodes a serine/threonine protein kinase that phosphorylates UPF1 to regulate nonsense-mediated mRNA decay and also functions in DNA damage response by phosphorylating p53. Mutations cause primary microcephaly with intellectual disability and developmental delay, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants, indicating that complete loss of SMG1 function is likely incompatible with normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SMG1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools