RPUSD4
Chr 11RNA pseudouridine synthase D4
The RPUSD4 protein is a pseudouridine synthase that modifies mitochondrial ribosomal RNA and tRNA, playing an essential role in mitochondrial ribosome assembly and translation, while also regulating nuclear pre-mRNA splicing through RNA modifications. Mutations cause autosomal recessive mitochondrial complex IV deficiency presenting in infancy with severe neurological deterioration, developmental delay, and multi-organ dysfunction. This gene shows very low constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
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
141 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 | 0 | 0 | 64 | 0 | 64 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 50 | 4 | 0 | 54 |
Likely Benign | 0 | 8 | 0 | 0 | 8 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 58 | 70 | 0 | 128 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RPUSD4 · 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