THO complex subunit 6 (THOC6)

THO complex subunit 6 (THOC6) is an integral component of the multi-protein THO complex, which is part of the larger TREX (Transcription/Export) complex. THOC6 functions as a scaffold protein within the THO complex, facilitating formation of the TREX tetramer in mammals. This complex plays a crucial role in coupling mRNA transcription and processing with its export from the nucleus, thereby ensuring mature mRNAs are efficiently and accurately exported to the cytoplasm. Disruptions in THOC6, such as missense or loss-of-function mutations, are associated with the neurodevelopmental disorder Beaulieu-Boycott-Innes syndrome, characterized by intellectual disability and variable congenital malformations. Molecular studies show that THOC6 is required for proper mRNA splicing and export, with disease-associated variants leading to impaired splicing fidelity and developmental defects[1][2][3][5]. THOC6 supports mRNA processing by acting as a core structural and scaffolding subunit within the TREX complex, a major assembly required for exporting mature mRNAs from the nucleoplasm to the cytoplasm. The function is particularly significant during brain development, where it appears to regulate neural proliferation and differentiation[2][3]. Homozygous or compound heterozygous mutations in THOC6 cause Beaulieu-Boycott-Innes syndrome (BBIS), typified by intellectual disability, microcephaly, and frequently accompanied by cardiac, renal, or craniofacial abnormalities, reflecting its essential biological function in neurodevelopment and organogenesis[1][2][3][5]. While THOC6 contains WD repeat domains (typically involved in protein–protein interactions), it is not an enzyme, receptor, ion channel, nor typical signaling effector. It is classified as part of the macromolecular THO complex (and thus TREX complex) and is best described as an "Other" cellular machinery protein[1][3]. There are currently no drugs or mechanism-of-action agents identified to act directly on THOC6, nor is it a canonical therapeutic target in disease (such as a receptor or enzyme); its disease importance is established via loss-of-function genetic studies in rare neurodevelopmental disorders[1][2][3].

Other names

BBISFSAP35WDR58WD repeat-containing protein 58functional spliceosome-associated protein 35MGC2655PSEC0006