protein
E3 ubiquitin-protein ligase TRIP12
Gene
TRIP12
Organism
Homo sapiens(9606)
Length
2067 aa
Mass
228,484 Da
TRIP12 is an E3 ubiquitin-protein ligase involved in the ubiquitin fusion degradation (UFD) pathway and DNA damage response (UniProt: Q14669). It mediates N-terminal ubiquitination of target proteins and acts as a suppressor of RNF168 to prevent excessive ubiquitinated chromatin accumulation at DNA damage sites. The protein also regulates degradation of CDKN2A isoform p19ARF/ARF, NAE1, SMARCE1, and ASXL1, with these functions modulated by interactions with regulatory proteins including MYC, TRADD, and SMARCC1.
TRIP12 is expressed across tissues and plays critical roles in cell cycle regulation and genomic stability. Mutations in TRIP12 are associated with Clark-Baraitser syndrome (CLABARS), an autosomal dominant condition characterized by intellectual disability, delayed psychomotor development, behavioral abnormalities, dysmorphic features, tall stature, obesity, and macrocephaly (UniProt: Q14669).
TRIP12 is classified as a syndromic autism risk gene (SFARI Cat 1), indicating a strong association with autism spectrum disorder within the context of systemic genetic syndromes such as Clark-Baraitser syndrome.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
High confidence — strong genetic evidence from multiple studies
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
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)
Disease associations
Clark-Baraitser syndromeCLABARS
An autosomal dominant disease characterized by intellectual disability, delayed psychomotor development, behavioral abnormalities, variable dysmorphic facial features, tall stature, obesity, and macrocephaly.
Sources
Last updated 5/6/2026, 5:25:10 AM