Human Gene Module / Chromosome 11 / CTNND1

CTNND1catenin delta 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 3
Rare Variants / Common Variants
12 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
11q12.1
Associated Disorders
-
Relevance to Autism

Whole-genome sequencing of 112 Chinese ASD patients and their non-ASD parents in Chang et al., 2024 identified two de novo missense variants in the CTNND1 gene; subsequent TADA analysis of de novo and inherited coding variants in this report identified CTNND1 as an ASD candidate gene with a P-value <0.001. A de novo nonsense variant in CTNND1 had previously been reported in a male ASD proband from the SPARK cohort (Zhou et al., 2022). Alharatani et al., 2020 reported eight novel protein-truncating CTNND1 variants, six of which were de novo, in 13 participants from nine families presenting with craniofacial dysmorphisms including cleft palate and hypodontia, as well as congenital cardiac anomalies, limb dysmorphologies and neurodevelopmental disorders; three of these individuals were reported to have autism spectrum disorder.

Molecular Function

This gene encodes a member of the Armadillo protein family, which function in adhesion between cells and signal transduction. Multiple translation initiation codons and alternative splicing result in many different isoforms being translated. Not all of the full-length natures of the described transcript variants have been determined. Read-through transcription also exists between this gene and the neighboring upstream thioredoxin-related transmembrane protein 2 (TMX2) gene.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CTNND1 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Reham Alharatani et al. (2020) No ASD, ADHD
2 Support - Zhou X et al. (2022) Yes -
3 Primary - Suhua Chang et al. () Yes -
Rare Variants   (12)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1030C>T p.Arg344Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.1269A>C p.Glu423Asp missense_variant De novo - Simplex 39126614 Suhua Chang et al. ()
c.2776A>G p.Met926Val missense_variant De novo - Simplex 39126614 Suhua Chang et al. ()
c.1381C>T p.Arg461Ter stop_gained De novo - Simplex 32196547 Reham Alharatani et al. (2020)
c.2389C>T p.Arg797Ter stop_gained De novo - Simplex 32196547 Reham Alharatani et al. (2020)
c.2702-5A>G - splice_region_variant De novo - Simplex 32196547 Reham Alharatani et al. (2020)
c.943C>T p.Arg315Cys missense_variant Familial Paternal Simplex 32196547 Reham Alharatani et al. (2020)
c.1595del p.Gly532AlafsTer6 frameshift_variant De novo - Simplex 32196547 Reham Alharatani et al. (2020)
c.2598_2601dup p.Ser868Ter stop_gained Familial Paternal Multiplex 32196547 Reham Alharatani et al. (2020)
c.443_444del p.Val148AspfsTer24 frameshift_variant Familial Maternal Simplex 32196547 Reham Alharatani et al. (2020)
c.1481_1485del p.Leu494ArgfsTer5 frameshift_variant Familial Maternal Multiplex 32196547 Reham Alharatani et al. (2020)
c.2737dup p.His913ProfsTer3 frameshift_variant De novo - Multiplex (monozygotic twins) 32196547 Reham Alharatani et al. (2020)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

10/1/2024
2

Initial score established: 2

Krishnan Probability Score

Score 0.48804768996439

Ranking 6834/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.99531268508893

Ranking 1503/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.94521152229068

Ranking 16380/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score 0.21219396394442

Ranking 4068/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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