RNF19A
Chr 8ring finger protein 19A, RBR E3 ubiquitin protein ligase
Also known as: RNF19
The protein functions as an E3 ubiquitin ligase that targets specific substrates including synphilin-1 and pathogenic SOD1 variants for proteasomal degradation. Mutations cause autosomal recessive spastic paraplegia, which primarily affects the corticospinal tracts leading to progressive lower limb spasticity and weakness. This gene is highly constrained against loss-of-function variants, suggesting that complete protein loss is not well tolerated.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative 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
134 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 | 36 | 0 | 36 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 72 | 6 | 0 | 78 |
Likely Benign | 0 | 2 | 0 | 0 | 2 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 0 | 74 | 43 | 1 | 118 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RNF19A · 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