AlphaFold predicted structure
TRIP12 · Q14669
Mean pLDDT
66.8/ 100
Low
1,992 residues
Confidence breakdown
- Very high(≥ 90)26%
- Confident(70–90)33%
- Low(50–70)7%
- Very low(< 50)35%
Open interactive 3D viewer
AlphaFold (Jumper et al., 2021) · CC BY 4.0
TRIP12
Chr 2q36.3thyroid hormone receptor interactor 12
- Aliases:
- KIAA0045, ULF, TRIPC
- MANE:
- ENST00000675903.1
Annotations refreshed 1 month ago.
Predicted protein structure
Clinical relevance (Genomics England PanelApp)
Diagnostic Grade (Green)
DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownFetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownIntellectual disability
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Disease associations (Open Targets)
Clark-Baraitser syndrome
0.79neurodegenerative disease
0.58hereditary disease
0.52Intellectual disability
0.51complex neurodevelopmental disorder
0.46neurodevelopmental disorder
0.45lysosomal storage disease
0.37Neurodevelopmental delay
0.34diabetes mellitus
0.27mouth disorder
0.26
Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.
Protein function (UniProt)
E3 ubiquitin-protein ligase TRIP12
E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair (PubMed:19028681, PubMed:22884692, PubMed:40419785). Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardless of the presence of lysine residues in target proteins (PubMed:19028681). Acts as a key regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor required for p53/TP53 activation under oncogenic stress (PubMed:20208519). In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation (PubMed:20208519). Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A (PubMed:20208519). Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation (PubMed:18627766). Ubiquitination and degradation of target proteins is regulated by interaction with proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction between TRIP12 and target proteins (PubMed:20829358). Mediates ubiquitination of ASXL1: following binding to N(6)-methyladenosine methylated DNA, ASXL1 is ubiquitinated by TRIP12, leading to its degradation and subsequent inactivation of the PR-DUB complex (PubMed:30982744)
Diseases associated with TRIP12
Curated MONDO disease pages that list TRIP12 among their top associated genes.