RNASEK
Chr 17ribonuclease K
The RNASEK protein is an endoribonuclease that regulates vacuolar H+-ATPase activity, which is essential for acidifying intracellular compartments and receptor-mediated endocytosis. Mutations cause MEND syndrome (mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma), a severe multisystem disorder with autosomal recessive inheritance. The condition involves intellectual disability, gastrointestinal dysfunction, hearing loss, and skin abnormalities with early childhood onset.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
RNASEK · 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