ArticleJournal of medical genetics2015
HACE1 deficiency causes an autosomal recessive neurodevelopmental syndrome.
Article in Journal of medical genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 44 citations in OpenAlex.
- Review
- Identification of a putative founder effect involving the HACE1:c.1396C>T variant in two Iranian families and review of reported cases.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Expanding the repertoire of loss-of-function variants in HACE1 causing complex spastic paraplegia: literature review and recommendations on clinical management.Human genomics · 2026Review
- Strabismus in Genetic Syndromes: A Review.Clinical & experimental ophthalmology · 2025Review
- Advances in genetic developmental and epileptic encephalopathies with movement disorders.Acta epileptologica · 2025Review
- A Missense Variant inGenes · 2024Article
- Article
- A Survey on the Expression of the Ubiquitin Proteasome System Components HECT- and RBR-E3 Ubiquitin Ligases and E2 Ubiquitin-Conjugating and E1 Ubiquitin-Activating Enzymes during Human Brain Development.International journal of molecular sciences · 2024Article
- Structural mechanisms of autoinhibition and substrate recognition by the ubiquitin ligase HACE1.Nature structural & molecular biology · 2024Article
- Previously Undescribed GrossGenes · 2022Article
- Hace1 overexpression mitigates myocardial hypoxia/reoxygenation injury via the effects on Keap1/Nrf2 pathway.In vitro cellular & developmental biology. Animal · 2022Article
- HACE1 builds molecular crosstalks between rare diseases and (more) common disorders.Clinical and translational medicine · 2022Article
- HACE1, GLRX5, and ELP2 gene variant cause spastic paraplegies.Acta neurologica Belgica · 2022Article
- Article
- Review
- Mitophagy in Human Diseases.International journal of molecular sciences · 2021Review
- Neurodevelopmental Disorders (NDD) Caused by Genomic Alterations of the Ubiquitin-Proteasome System (UPS): the Possible Contribution of Immune Dysregulation to Disease Pathogenesis.Frontiers in molecular neuroscience · 2021Review
- Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview.Frontiers in molecular biosciences · 2021Review
- TGF-β-Induced Phosphorylation of Usp9X Stabilizes Ankyrin-G and Regulates Dendritic Spine Development and Maintenance.Cell reports · 2020Article
- HECT E3 ubiquitin ligases - emerging insights into their biological roles and disease relevance.Journal of cell science · 2020Review
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundThe genetic aetiology of neurodevelopmental defects is extremely diverse, and the lack of distinctive phenotypic features means that genetic criteria are often required for accurate diagnostic classification. We aimed to identify the causative genetic lesions in two families in which eight affected individuals displayed variable learning disability, spasticity and abnormal gait.
methodsAutosomal recessive inheritance was suggested by consanguinity in one family and by sibling recurrences with normal parents in the second. Autozygosity mapping and exome sequencing, respectively, were used to identify the causative gene.
resultsIn both families, biallelic loss-of-function mutations in HACE1 were identified. HACE1 is an E3 ubiquitin ligase that regulates the activity of cellular GTPases, including Rac1 and members of the Rab family. In the consanguineous family, a homozygous mutation p.R219* predicted a truncated protein entirely lacking its catalytic domain. In the other family, compound heterozygosity for nonsense mutation p.R748* and a 20-nt insertion interrupting the catalytic homologous to the E6-AP carboxyl terminus (HECT) domain was present; western blot analysis of patient cells revealed an absence of detectable HACE1 protein.
conclusionHACE1 mutations underlie a new autosomal recessive neurodevelopmental disorder. Previous studies have implicated HACE1 as a tumour suppressor gene; however, since cancer predisposition was not observed either in homozygous or heterozygous mutation carriers, this concept may require re-evaluation.
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Registered trials
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.