UPF2
Chr 10UPF2 regulator of nonsense mediated mRNA decay
Also known as: HUPF2, RENT2, smg-3
UPF2 encodes a protein essential for nonsense-mediated mRNA decay (NMD), a cellular quality control mechanism that degrades mRNAs containing premature stop codons by forming surveillance complexes with UPF1 and UPF3 proteins. Mutations cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in early childhood. This gene is extremely intolerant to loss-of-function mutations, reflecting its critical role in mRNA surveillance and cellular homeostasis.
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
199 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 0 | 17 | 0 | 18 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 125 | 10 | 0 | 135 |
Likely Benign | 0 | 2 | 5 | 3 | 10 |
Benign | 0 | 0 | 4 | 4 | 8 |
| Total | 1 | 127 | 36 | 7 | 171 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
UPF2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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