RNF128
Chr Xring finger protein 128
Also known as: GRAIL
RNF128 encodes an E3 ubiquitin ligase that regulates immune responses by targeting various proteins for degradation, including components involved in T-cell activation, cytoskeletal dynamics, and innate immunity. Mutations in RNF128 cause autosomal recessive developmental and epileptic encephalopathy with microcephaly. The gene shows moderate constraint against loss-of-function variants, suggesting some tolerance to heterozygous disruption.
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 gain-of-function.
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
219 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 | 61 | 0 | 61 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 57 | 4 | 0 | 61 |
Likely Benign | 0 | 3 | 1 | 1 | 5 |
Benign | 0 | 1 | 0 | 1 | 2 |
Conflicting | — | 1 | |||
| Total | 0 | 61 | 69 | 2 | 133 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RNF128 · 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