ArticleThe Journal of clinical investigation2022
GIGYF1 disruption associates with autism and impaired IGF-1R signaling.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Discovery of obesity genes through cross-ancestry analysis.Nature communications · 2025Pooled it
- Evidence supporting the role of GIGYF2 in synapse development and autism.Molecular psychiatry · 2026Article
- Imputation of fluid intelligence scores reduces ascertainment bias and increases power for analyses of common and rare variants.Nature genetics · 2026Article
- Monoallelic loss-of-function variants in ZNF536 are associated with a neurodevelopmental disorder with prominent behavioral features.American journal of human genetics · 2026Article
- MSL2 disruption leads to autism-like behaviors, impairs neurogenesis, and alters histone H4K16 acetylation.Cellular and molecular life sciences : CMLS · 2026Article
- Ethnic genomic differences in esophageal squamous cell carcinoma: Whole-exome sequencing of Han and Kazakh populations in China.World journal of gastroenterology · 2025Article
- The Possible Role of Postnatal Biphasic Dysregulation of IGF-1 Tone in the Etiology of Idiopathic Autism Spectrum Disorder.International journal of molecular sciences · 2025Review
- Article
- Associations between amino acid levels and autism spectrum disorder severity.BMC psychiatry · 2025Article
- Review
- Post-transcriptional dysregulation in autism, schizophrenia, and bipolar disorder.Journal of biomedical research · 2024Article
- Review
- Unveiling the role of IGF1R in autism spectrum disorder: a multi-omics approach to decipher common pathogenic mechanisms in the IGF signaling pathway.Frontiers in genetics · 2024Article
- EHD1-dependent traffic of IGF-1 receptor to the cell surface is essential for Ewing sarcoma tumorigenesis and metastasis.Communications biology · 2023Article
- Low Expression of GIGYF1 Inhibits Metastasis, Proliferation, and Promotes Apoptosis and Autophagy of Gastric Cancer Cells.International journal of medical sciences · 2023Article
- GIGYF1-disturbed IGF-1R recycling: a potential contributor to autism spectrum disorder pathogenesis?The Journal of clinical investigation · 2022Article
- Machine learning uncovers novel sex-specific dementia biomarkers linked to autism and eye diseases.Journal of Alzheimer's disease reportsArticle
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Authors and funding
34 authors at 13 institutions in 6 countries.
Funding
Abstract
Autism spectrum disorder (ASD) represents a group of neurodevelopmental phenotypes with a strong genetic component. An excess of likely gene-disruptive (LGD) mutations in GIGYF1 was implicated in ASD. Here, we report that GIGYF1 is the second-most mutated gene among known ASD high-confidence risk genes. We investigated the inheritance of 46 GIGYF1 LGD variants, including the highly recurrent mutation c.333del:p.L111Rfs*234. Inherited GIGYF1 heterozygous LGD variants were 1.8 times more common than de novo mutations. Among individuals with ASD, cognitive impairments were less likely in those with GIGYF1 LGD variants relative to those with other high-confidence gene mutations. Using a Gigyf1 conditional KO mouse model, we showed that haploinsufficiency in the developing brain led to social impairments without significant cognitive impairments. In contrast, homozygous mice showed more severe social disability as well as cognitive impairments. Gigyf1 deficiency in mice led to a reduction in the number of upper-layer cortical neurons, accompanied by a decrease in proliferation and increase in differentiation of neural progenitor cells. We showed that GIGYF1 regulated the recycling of IGF-1R to the cell surface. KO of GIGYF1 led to a decreased level of IGF-1R on the cell surface, disrupting the IGF-1R/ERK signaling pathway. In summary, our findings show that GIGYF1 is a regulator of IGF-1R recycling. Haploinsufficiency of GIGYF1 was associated with autistic behavior, likely through interference with IGF-1R/ERK signaling pathway.
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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.