ArticleHuman genetics2017
Haploinsufficiency of the E3 ubiquitin-protein ligase gene TRIP12 causes intellectual disability with or without autism spectrum disorders, speech delay, and dysmorphic features.
Article in Human genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 62 citations in OpenAlex.
- Review
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- Multilayered genetic dissection of autism: insights from whole-exome sequencing, molecular karyotyping, and cytogenetic analyses in a small Turkish cohort.Neurogenetics · 2025Article
- Novel TRIP12 variants in two Lebanese patients with neurodevelopmental delay.BMC medical genomics · 2025Article
- Neurodevelopmental Phenotype Associated withGenes · 2025Article
- Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12.Cell reports · 2025Article
- TRIP12 structures reveal HECT E3 formation of K29 linkages and branched ubiquitin chains.Nature structural & molecular biology · 2025Article
- TRIP12's role in the governance of DNA polymerase β involvement in DNA damage response and repair.Nucleic acids research · 2025Article
- The Role of a Novel TRIP12 Mutation in Intellectual Disability: A Molecular and Clinical Investigation in Multiplex Family.Journal of molecular neuroscience : MN · 2025Article
- The Hao-Fountain syndrome protein USP7 regulates neuronal connectivity in the brain via a novel p53-independent ubiquitin signaling pathway.Cell reports · 2025Article
- Ubiquitin-Proteasome-Mediated Protein Degradation and Disorders of the Central Nervous System.International journal of molecular sciences · 2025Review
- Prenatal whole-exome sequencing for fetal structural anomalies: a retrospective analysis of 145 Chinese cases.BMC medical genomics · 2023Article
- Gbb glutathionylation promotes its proteasome-mediated degradation to inhibit synapse growth.The Journal of cell biology · 2023Article
- The neurodevelopmental and facial phenotype in individuals with a TRIP12 variant.European journal of human genetics : EJHG · 2023Article
- The HAPSTR2 retrogene buffers stress signaling and resilience in mammals.Nature communications · 2023Article
- Novel Synonymous and Frameshift Variants in theNeurology. Genetics · 2022Article
- Activity-based probe profiling of RNF12 E3 ubiquitin ligase function in Tonne-Kalscheuer syndrome.Life science alliance · 2022Article
- Targeting UBR5 in hepatocellular carcinoma cells and precise treatment via echinacoside nanodelivery.Cellular & molecular biology letters · 2022Article
- Complex Diagnostics of Non-Specific Intellectual Developmental Disorder.International journal of molecular sciences · 2022Article
- De novo missense variants in FBXO11 alter its protein expression and subcellular localization.Human molecular genetics · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
38 authors at 12 institutions in 5 countries.
Funding
Abstract
Impairment of ubiquitin-proteasome system activity involving ubiquitin ligase genes UBE3A, UBE3B, and HUWE1 and deubiquitinating enzyme genes USP7 and USP9X has been reported in patients with neurodevelopmental delays. To date, only a handful of single-nucleotide variants (SNVs) and copy-number variants (CNVs) involving TRIP12, encoding a member of the HECT domain E3 ubiquitin ligases family on chromosome 2q36.3 have been reported. Using chromosomal microarray analysis and whole-exome sequencing (WES), we have identified, respectively, five deletion CNVs and four inactivating SNVs (two frameshifts, one missense, and one splicing) in TRIP12. Seven of these variants were found to be de novo; parental studies could not be completed in two families. Quantitative PCR analyses of the splicing mutation showed a dramatically decreased level of TRIP12 mRNA in the proband compared to the family controls, indicating a loss-of-function mechanism. The shared clinical features include intellectual disability with or without autistic spectrum disorders, speech delay, and facial dysmorphism. Our findings demonstrate that E3 ubiquitin ligase TRIP12 plays an important role in nervous system development and function. The nine presented pathogenic variants further document that TRIP12 haploinsufficiency causes a childhood-onset neurodevelopmental disorder. Finally, our data enable expansion of the phenotypic spectrum of ubiquitin-proteasome dependent disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.