DIS3
Chr 13DIS3 exosome endoribonuclease and 3'-5' exoribonuclease
Also known as: 2810028N01Rik, EXOSC11, KIAA1008, RRP44, dis3p
The DIS3 protein functions as the catalytic component of the RNA exosome complex, performing 3'-5' exoribonuclease activity essential for RNA processing, degradation, and cellular RNA surveillance in both the nucleus and cytoplasm. Mutations in DIS3 cause multiple mitochondrial dysfunctions syndrome 7, an autosomal recessive disorder characterized by early-onset developmental delay, intellectual disability, seizures, and mitochondrial dysfunction. This gene shows extreme intolerance to loss-of-function variants, indicating that even single functional copies may be insufficient for normal cellular function.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
DIS3 · 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