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Intellectual disability syndromic and non-syndromic v2.80 GTF3C1 chirag patel gene: GTF3C1 was added
gene: GTF3C1 was added to Intellectual disability syndromic and non-syndromic. Sources: Other
Mode of inheritance for gene: GTF3C1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GTF3C1 were set to Neurodevelopmental disorder, MONDO:0700092, GTF3C1-related
Review for gene: GTF3C1 was set to AMBER
Added comment: ESHG 2026

6 individuals from 6 unrelated families (4 consanguineous) with biallelic variants in GTF3C1 which segregated with disease (6 missense, 1 nonsense). Phenotype included developmental delay, intellectual disability, microcephaly, cerebellar atrophy/hypoplasia, abnormal corpus callosum, arthrogryposis, and variable craniofacial features.

GTF3C1 encodes a subunit within the general Transcription Factor IIIC (TFIIIC), which is involved general transcription factor activity via recruitment of RNA polymerase III for target gene transcription. Two other TFIIIC subunits, GTF3C3 and GTF3C5, have been implicated in neurodevelopmental disorders. Molecular modelling suggested missense variants disrupt intramolecular interactions, causing instability of the TFIIIC complex. Proteomic analysis using patient cell lines revealed significantly reduced GTF3C1 protein. A relative complex abundance assay demonstrated the five other subunits of the TFIIIC complex were also reduced, and suggests a loss-of-function mechanism. Gtf3c1 knockdown in mouse brain revealed impaired neuronal production and cell cycle exit.
Sources: Other
Intellectual disability syndromic and non-syndromic v2.0 GTF3C3 Gene migrated from ENSG00000119041 to ENSG00000119041 (gene set migration)
Intellectual disability syndromic and non-syndromic v1.145 GTF3C3 Zornitza Stark Phenotypes for gene: GTF3C3 were changed from Neurodevelopmental disorder MONDO:0700092, GTF3C3-related to Neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizures, MIM# 621201
Intellectual disability syndromic and non-syndromic v1.144 GTF3C3 Zornitza Stark edited their review of gene: GTF3C3: Changed phenotypes: Neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizures, MIM# 621201
Intellectual disability syndromic and non-syndromic v1.44 GTF3C3 chirag patel reviewed gene: GTF3C3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39636576; Phenotypes: Neurodevelopmental disorder MONDO:0700092, GTF3C3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.4763 GTF3C3 Zornitza Stark Phenotypes for gene: GTF3C3 were changed from Global developmental delay; Intellectual disability; Seizures to Neurodevelopmental disorder MONDO:0700092, GTF3C3-related
Intellectual disability syndromic and non-syndromic v0.4762 GTF3C3 Zornitza Stark edited their review of gene: GTF3C3: Changed phenotypes: Neurodevelopmental disorder MONDO:0700092, GTF3C3-related
Intellectual disability syndromic and non-syndromic v0.2017 GTF3C3 Zornitza Stark Marked gene: GTF3C3 as ready
Intellectual disability syndromic and non-syndromic v0.2017 GTF3C3 Zornitza Stark Gene: gtf3c3 has been classified as Green List (High Evidence).
Intellectual disability syndromic and non-syndromic v0.2017 GTF3C3 Zornitza Stark Phenotypes for gene: GTF3C3 were changed from Global developmental delay; Intellectual disability; Seizures to Global developmental delay; Intellectual disability; Seizures
Intellectual disability syndromic and non-syndromic v0.2016 GTF3C3 Zornitza Stark Phenotypes for gene: GTF3C3 were changed from to Global developmental delay; Intellectual disability; Seizures
Intellectual disability syndromic and non-syndromic v0.2015 GTF3C3 Zornitza Stark Publications for gene: GTF3C3 were set to
Intellectual disability syndromic and non-syndromic v0.2014 GTF3C3 Zornitza Stark Mode of inheritance for gene: GTF3C3 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.2013 GTF3C3 Zornitza Stark reviewed gene: GTF3C3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28940097, 28097321, 30552426; Phenotypes: Global developmental delay, Intellectual disability, Seizures; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability syndromic and non-syndromic v0.0 GTF3C3 Zornitza Stark gene: GTF3C3 was added
gene: GTF3C3 was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland
Mode of inheritance for gene: GTF3C3 was set to Unknown