Human Gene Module / Chromosome 5 / CTNND2

CTNND2Catenin (cadherin-associated protein), delta 2

Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 4
Rare Variants / Common Variants
16 / 0
Aliases
CTNND2, GT24,  NPRAP
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
5p15.2
Associated 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.

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
2

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).

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.

04-01-2017
2

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)
5p15.2 25 Deletion-Duplication 41  /  250
Animal Models associated with CTNND2(1 Models)
Ctnnd2_1_KO_HM Genetic
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
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