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| Mendeliome v2.184 | GIT1 | Sarah Milton Classified gene: GIT1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.184 | GIT1 | Sarah Milton Gene: git1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.183 | GIT1 |
Sarah Milton gene: GIT1 was added gene: GIT1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GIT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GIT1 were set to 42360756 Phenotypes for gene: GIT1 were set to Neurodevelopmental disorder, MONDO:0700092, GIT1-related Review for gene: GIT1 was set to GREEN Added comment: GIT1 encodes G-protein-coupled receptor kinase-interacting protein 1 which is a scaffold protein that plays roles in the actin cytoskeletal dynamics, focal adhesion assembly, membrane trafficking, intracellular signalling and neuronal development. PMID 42360756 reports nine individuals from three families with biallelic loss-of-function GIT1 variants presenting with microcephaly, severe developmental delay/intellectual disability, seizures, enlarged ventricles and variable other congenital brain anomalies, facial dysmorphism and intrauterine growth restriction/poor growth. 2 of the families had a shared haplotype and the same homozygous variant with the third family unrelated with a different loss of function variant. GIT1 is constrained for loss of function in gnomAD v4, there are no homozygous loss of function individuals present. Extensive functional studies support the association with zebrafish knock‑down recapitulates microcephaly and is rescued by wild‑type human GIT1 mRNA but not mRNA containing variants from affected patients, knockout mice have microcephaly and developmental delay, patient fibroblasts lack GIT1 protein and show reduced actin‑cytoskeleton dynamics. Sources: Literature |
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