TRIP12
Chr 2ADthyroid hormone receptor interactor 12
Also known as: MRD49, TRIP-12, TRIPC, ULF
The encoded E3 ubiquitin-protein ligase degrades the p19ARF tumor suppressor isoform and regulates USP7 stability in DNA damage response pathways. Loss-of-function mutations cause autosomal dominant intellectual developmental disorder. The gene is extremely intolerant to loss-of-function variants, indicating haploinsufficiency as the disease mechanism.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
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
567 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 | 36 | 1 | 26 | 0 | 63 |
Likely Pathogenic | 13 | 6 | 5 | 0 | 24 |
VUS | 4 | 292 | 30 | 0 | 326 |
Likely Benign | 0 | 31 | 12 | 41 | 84 |
Benign | 0 | 0 | 2 | 2 | 4 |
Conflicting | — | 5 | |||
| Total | 53 | 330 | 75 | 43 | 506 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TRIP12 · 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
External Resources
Links to major genomics databases and tools