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| Genetic Epilepsy v1.112 | C12orf66 | Zornitza Stark Phenotypes for gene: C12orf66 were changed from Neurodevelopmental disorder MONDO:0700092 to Intellectual developmental disorder, autosomal recessive 83, MIM# 621100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v1.111 | C12orf66 | Zornitza Stark edited their review of gene: C12orf66: Changed rating: GREEN; Changed phenotypes: Intellectual developmental disorder, autosomal recessive 83, MIM# 621100; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v1.108 | C12orf66 | Zornitza Stark Marked gene: C12orf66 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v1.108 | C12orf66 | Zornitza Stark Added comment: Comment when marking as ready: HGNC approved name is KICS2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v1.108 | C12orf66 | Zornitza Stark Gene: c12orf66 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v1.108 | C12orf66 | Zornitza Stark Tag new gene name tag was added to gene: C12orf66. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v1.108 | C12orf66 | Chirag Patel Classified gene: C12orf66 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v1.108 | C12orf66 | Chirag Patel Gene: c12orf66 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v1.108 | C12orf66 | Chirag Patel Classified gene: C12orf66 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v1.108 | C12orf66 | Chirag Patel Gene: c12orf66 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v1.107 | C12orf66 |
Chirag Patel gene: C12orf66 was added gene: C12orf66 was added to Genetic Epilepsy. Sources: Literature Mode of inheritance for gene: C12orf66 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C12orf66 were set to PMID: 39824192 Phenotypes for gene: C12orf66 were set to Neurodevelopmental disorder MONDO:0700092 Review for gene: C12orf66 was set to GREEN Added comment: 11 individuals from 8 families with mild to moderate intellectual disability (11/11), epilepsy (8/11), hearing impairment (3/11), macrocephaly (2/11), facial dysmorphism (6/6). WES/WGS identified biallelic variants (missense, nonsense, and large deletion) in KICS2 gene (aka C12ORF66). The KICS2 protein is part of the KICSTOR complex which recruits GATOR1 to lysosomes and inhibits mTORC1 activity. Overactivation of the mTORC1 pathway is a recognized cause of several neurodevelopmental disorders. The variants in the individuals partly affected KICS2 stability, compromised KICSTOR complex formation, and demonstrated a deleterious impact on nutrient-dependent mTORC1 regulation of 4EBP1 and S6K. Phosphoproteome analyses extended these findings to show that KICS2 variants changed the mTORC1 proteome, affecting proteins that function in translation, splicing, and ciliogenesis. Depletion of Kics2 in zebrafish resulted in ciliary dysfunction consistent with a role of mTORC1 in cilia biology. Sources: Literature |
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