Relevance to Autism

Two de novo variants (one nonsense, one missense) in the CTNNB1 gene were identified in unrelated simplex ASD cases (PMIDs 22495309 and 23160955). Three de novo LoF variants in CTNNB1 (two frameshift, one nonsense) have been identified in unrelated patients with a similar phenotypic profile: severe ID, absent or very limited speech, microcephaly, and spasticity (PMIDs 23033978 and 24614104). De novo LoF variants in CTNNB1 were identified in a total of six patients from the Deciphering Developmental Disorders study (PMID 25533962). A de novo LoF variant in CTNNB1 was identifed in a proband from the Pediatric Cardiac Genetics Consortium who presented with ASD, developmental delay, and intellectual disability in addition to congenital heart disease (Homsy et al., 2015). Conditional knockout mice with CTNNB1-deficient parvalbumin interneurons exhibited significantly impaired object recognition and social interactions, elevated repetitive behaviors, and increased anxiety (Dong et al., 2016). Two de novo protein-truncating variants in CTNNB1 were identified in ASD probands from the Autism Sequencing Consortium in Satterstrom et al., 2020; two protein-truncating variants in this gene were also observed in case samples from the Danish iPSYCH study in the same report. TADA analysis of de novo variants from the Simons Simplex Collection and the Autism Sequencing Consortium and protein-truncating variants from iPSYCH in Satterstrom et al., 2020 identified CTNNB1 as a candidate gene with a false discovery rate (FDR) 0.01. A two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in Zhou et al., 2022 identified CTNNB1 as a gene reaching study-wide significance based on 5,754 constraint genes (P < 8.69E-06).

Molecular Function

The protein encoded by this gene is part of a complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells. The encoded protein also anchors the actin cytoskeleton and may be responsible for transmitting the contact inhibition signal that causes cells to stop dividing once the epithelial sheet is complete. Finally, this protein binds to the product of the APC gene, which is mutated in adenomatous polyposis of the colon.

External Links

References

Model Summary

This model specifically deletes CTNNB1 in parvalbumin interneurons.

References