RC3H2
Chr 9ring finger and CCCH-type domains 2
Also known as: MNAB, RNF164
RC3H2 encodes a post-transcriptional repressor that binds to conserved decay elements in mRNAs to promote their degradation, regulates microRNA processing, and functions as a ubiquitin E3 ligase involved in protein polyubiquitination. Mutations cause autosomal dominant neurodevelopmental disorder through loss-of-function mechanisms. The protein is highly intolerant to loss-of-function variants, indicating haploinsufficiency as the likely pathogenic mechanism.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
182 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 | 28 | 0 | 28 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 1 | 113 | 4 | 0 | 118 |
Likely Benign | 0 | 0 | 0 | 2 | 2 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 1 | 113 | 33 | 2 | 149 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RC3H2 · 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