CTNND2Catenin (cadherin-associated protein), delta 2
Autism Reports / Total Reports
2 / 4Rare Variants / Common Variants
16 / 0Aliases
CTNND2, GT24, NPRAPAssociated Syndromes
-Genetic Category
Rare Single Gene MutationChromosome Band
5p15.2Associated Disorders
-Relevance to Autism
Missense variants at conserved residues of the CTNND2 gene were found to be significantly more frequent in autism cases than in controls (P=0.04 vs. 1000 Genomes Project; P=7.8E-04 vs. Exome Variant Server); several of these missense variants exhibited loss-of-function effects by functional analysis in zebrafish embryos and cultured hippocampal neurons (Turner et al., 2015).
Molecular Function
This gene encodes an adhesive junction associated protein of the armadillo/beta-catenin superfamily and is implicated in brain and eye development and cancer formation.
External Links
- Reports (4)
- Variants (16)
- Gene Score
- Associated CNVs (1)
- Associated Animal Models (1)
- Protein Interactions (16)
Reports related to CTNND2 (4 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Primary | Loss of -catenin function in severe autism. | Turner TN , et al. (2015) | Yes | - |
| 2 | Support | De novo genic mutations among a Chinese autism spectrum disorder cohort. | Wang T , et al. (2016) | Yes | - |
| 3 | Support | The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies. | Redin C , et al. (2016) | No | - |
| 4 | Support | Whole-Genome Sequencing of Cytogenetically Balanced Chromosome Translocations Identifies Potentially Pathological Gene Disruptions and Highlights t... | Nilsson D , et al. (2016) | No | - |
Rare Variants (16)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.100G>A | p.Gly34Ser | missense_variant | Familial | Maternal | Multiplex | 25807484 | Turner TN , et al. (2015) | |
| c.2137C>T | p.Arg713Cys | missense_variant | Familial | Maternal | Multiplex | 25807484 | Turner TN , et al. (2015) | |
| c.100G>A | p.Gly34Ser | missense_variant | Unknown | - | Unknown | 25807484 | Turner TN , et al. (2015) | |
| c.2137C>T | p.Arg713Cys | missense_variant | Unknown | - | Unknown | 25807484 | Turner TN , et al. (2015) | |
| c.566C>T | p.Pro189Leu | missense_variant | Unknown | - | Unknown | 25807484 | Turner TN , et al. (2015) | |
| c.671C>T | p.Pro224Leu | missense_variant | Unknown | - | Unknown | 25807484 | Turner TN , et al. (2015) | |
| c.823G>T | p.Gly275Cys | missense_variant | Unknown | - | Unknown | 25807484 | Turner TN , et al. (2015) | |
| c.1361G>A | p.Arg454His | missense_variant | Unknown | - | Unknown | 25807484 | Turner TN , et al. (2015) | |
| c.2585C>T | p.Thr862Met | missense_variant | Unknown | - | Unknown | 25807484 | Turner TN , et al. (2015) | |
| c.1520A>C | p.Gln507Pro | missense_variant | Unknown | - | Simplex | 25807484 | Turner TN , et al. (2015) | |
| - | - | copy_number_loss | Familial | Maternal | Unknown | 25807484 | Turner TN , et al. (2015) | |
| - | - | copy_number_loss | Familial | Paternal | Unknown | 25807484 | Turner TN , et al. (2015) | |
| c.2467G>A | p.Asp823Asn | missense_variant | Familial | Paternal | - | 27824329 | Wang T , et al. (2016) | |
| c.2087C>T | p.Ser696Leu | missense_variant | Familial | Paternal | - | 27824329 | Wang T , et al. (2016) | |
| - | - | translocation | De novo | - | - | 27841880 | Redin C , et al. (2016) | |
| - | - | translocation | Familial | Maternal | Multi-generational | 27862604 | Nilsson D , et al. (2016) |
Common Variants
No common variants reported.
SFARI Gene score
Strong Candidate
Exome sequencing of 13 unrelated female ASD patients from multiplex families with severe autism identified two missense variants in the CTNND2 gene. Additional sequencing of ASD cases and controls determined that missense variants at conserved residues of the CTNND2 gene were found to be significantly more frequent in autism cases than in controls (P=0.04 vs. 1000 Genomes Project; P=7.8E-04 vs. Exome Variant Server). Although segregation of these variants was incomplete or not determined in many cases, functional analysis of ASD-associated CTNND2 missense variants in zebrafish embryos and cultured hippocampal neurons identified several missense variants that exhibited loss-of-function effects (PMID 25807484). In the same report, a comparison of dosage imbalances (deletions, duplications, and unbalanced translocations) affecting the CTNND2 gene in 19,556 cases and 13,898 controls from PMID 22521361 found 25 instances in cases and three in controls, corresponding to an odds ratio of 5.9 (P=4.10 x 10-4).
criteria met
See SFARI Gene'scoring criteriaWe 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.
04-01-2017
Initial score established: 2
Description
Exome sequencing of 13 unrelated female ASD patients from multiplex families with severe autism identified two missense variants in the CTNND2 gene. Additional sequencing of ASD cases and controls determined that missense variants at conserved residues of the CTNND2 gene were found to be significantly more frequent in autism cases than in controls (P=0.04 vs. 1000 Genomes Project; P=7.8E-04 vs. Exome Variant Server). Although segregation of these variants was incomplete or not determined in many cases, functional analysis of ASD-associated CTNND2 missense variants in zebrafish embryos and cultured hippocampal neurons identified several missense variants that exhibited loss-of-function effects (PMID 25807484). In the same report, a comparison of dosage imbalances (deletions, duplications, and unbalanced translocations) affecting the CTNND2 gene in 19,556 cases and 13,898 controls from PMID 22521361 found 25 instances in cases and three in controls, corresponding to an odds ratio of 5.9 (P=4.10 x 10-4).
CNVs associated with CTNND2(1 CNVs)
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| 5p15.2 | 25 | Deletion-Duplication | 41 / 250 |
Animal Models associated with CTNND2(1 Models)
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| Ctnnd2_1_KO_HM | Genetic |
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
Interaction Table
| Interactor Symbol | Interactor Name | Interactor Organism | Interactor Type | Entrez ID | Uniprot ID |
|---|---|---|---|---|---|
| ARHGEF28 | Rho guanine nucleotide exchange factor (GEF) 28 | Human | Protein Binding | 64283 | Q8N1W1 |
| CCDC85A | coiled-coil domain containing 85A | Human | Protein Binding | 114800 | Q96PX6 |
| CCDC85B | coiled-coil domain containing 85B | Human | Protein Binding | 11007 | Q15834 |
| Cttn | cortactin | Mouse | Protein Binding | 13043 | Q60598 |
| Dact1 | dapper homolog 1, antagonist of beta-catenin (xenopus) | Mouse | Protein Binding | 59036 | Q8R4A3 |
| Dact2 | dapper homolog 2, antagonist of beta-catenin (xenopus) | Mouse | Protein Binding | 240025 | Q7TN08 |
| DNM1 | dynamin 1 | Human | Protein Binding | 1759 | Q05193 |
| GCH1 | GTP cyclohydrolase 1 | Human | Protein Binding | 2643 | P30793 |
| GLTP | glycolipid transfer protein | Human | Protein Binding | 51228 | Q9NZD2 |
| Grip2 | glutamate receptor interacting protein 2 | Rat | Protein Binding | 171571 | Q9WTW1 |
| HES1 | hairy and enhancer of split 1, (Drosophila) | Human | DNA Binding | 3280 | Q14469 |
| LNX1 | ligand of numb-protein X 1, E3 ubiquitin protein ligase | Human | Protein Modification | 84708 | Q8TBB1 |
| LRRC7 | leucine rich repeat containing 7 | Human | Protein Binding | 57554 | Q96NW7 |
| Pdzd2 | PDZ domain containing 2 | Rat | Protein Binding | 65034 | Q9QZR8 |
| PRR36 | proline rich 36 | Human | Protein Binding | 80164 | Q9H6K5 |
| Sphk1 | sphingosine kinase 1 | Mouse | Protein Binding | 20698 | Q8CI15 |