EXOSC4
Chr 8exosome component 4
The EXOSC4 protein is a non-catalytic component of the RNA exosome complex that processes and degrades various cellular RNAs, including rRNA maturation, mRNA turnover, and elimination of aberrant transcripts. Mutations in EXOSC4 cause autosomal recessive short stature, hearing loss, retinitis pigmentosa, and distinctive facies (SHRF) syndrome, affecting growth, sensory organs, and development. This gene shows relatively low constraint to loss-of-function variation, suggesting the recessive inheritance pattern aligns with its tolerance profile.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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
EXOSC4 · 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