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| Intellectual disability syndromic and non-syndromic v2.99 | THAP12 | chirag patel Marked gene: THAP12 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v2.99 | THAP12 | chirag patel Gene: thap12 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability syndromic and non-syndromic v2.99 | THAP12 |
chirag patel gene: THAP12 was added gene: THAP12 was added to Intellectual disability syndromic and non-syndromic. Sources: Other Mode of inheritance for gene: THAP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: THAP12 were set to Neurodevelopmental disorder, MONDO:0700092, THAP12-related Review for gene: THAP12 was set to RED Added comment: ESHG 2026 2 siblings from 1 family with compound heterozygous variants in THAP12 (1 missense, 1 frameshift), presenting with refractory early onset epilepsy, severe developmental delay and hypotonia, and microcephaly. ChIP-seq confirmed the role of THAP12 as a transcriptional activator of genes essential for proliferation, apoptosis, and mitochondrial function in HEK293FT cells. In silico predictions (AlphaFold 3) showed that THAP12 forms homodimers, enabling it to bind DNA. The patient variants were shown to lead to a significant reduction in THAP12 protein level, suggesting a loss-of-function mechanism. Mouse models show embryonic lethality in both Thap12-KO and models harbouring patient specific alleles. Zebrafish models showed THAP12 is primarily expressed in cycling neural progenitors, and loss-of-function models phenocopy the clinical presentation with microcephaly, abnormal neural activity, and seizure like-behaviour. Sources: Other |
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