• 1
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
CTNND2 (HGNC:2516) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
catenin delta 2
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
NPRAP, GT24
%HI
5.83(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.1(Read more about gnomAD LOEUF score)
Cytoband
5p15.2
Genomic Coordinates
GRCh37/hg19: chr5:10971948-11904558 NCBI Ensembl UCSC
GRCh38/hg38: chr5:10971836-11904446 NCBI Ensembl UCSC
MANE Select Transcript
NM_001332.4 ENST00000304623.13 (Read more about MANE Select)
Function
Has a critical role in neuronal development, particularly in the formation and/or maintenance of dendritic spines and synapses (PubMed:25807484). Involved in the regulation of Wnt signaling (PubMed:25807484). It probably acts on beta-catenin turnover, facilitating beta-catenin interaction with GSK3B, phosphorylation, ubiquitination and degradation (By similarity). Functions as a transcriptional activator when bound to ZBTB33 (By similarity). May be involved in neuronal cell adhesion and tissue m... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-1869
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Little Evidence for Haploinsufficiency (1)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
10/12/2021

Haploinsufficiency (HI) Score Details

HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • Complex Neurodevelopmental Disorder Monarch
HI Evidence:
  • PUBMED: 25106414
    Asadollahi et al (2014) report a de novo 113 kb out-of-frame deletion of exons 4-7 (chr5:11,431,816-11,545,23, confirmed by MLPA) in an 11 year old female with borderline intellectual disability (full-scale IQ 77), learning difficulties, short attention, social-emotional issues, and mild facial dysmorphism (Decipher ID=284528). Sanger sequencing in the patient did not reveal an additional pathogenic variant of the gene. Authors also summarized three further patients with exonic deletions limited to CTNND2 and neurodevelopmental features in the DECIPHER database: 248402, out-of-frame exons 2-8 deletion; 271234, out-of-frame exon 3 deletion; both inherited from parent with low normal IQ. DECIPHER case 269928 was found to have an exon 1-3 deletion, however carrier mother had no specific features.
  • PUBMED: 25807484
    Turner et al (2015) performed exome sequencing on 13 females with autism and identified 2 missense variants in the CTNND2 gene. To further explore variation in this gene, they sequenced CTNND2 in 362 additional autism families and identified 7 variants (additional observations of the original 2 missense variants, plus 5 novel missense variants). The authors also identified12 CNVs (10 deletions, 2 duplications) involving the CTNND2 gene in patients with autism from the literature, from the clinical cytogenetics laboratories at Emory University and Baylor College of Medicine, and from the Autism Genetic Resource Exchange (AGRE). Seven of the 10 listed deletions were focal deletions within CTNND2 overlapping one or more exons; 1 was de novo, 3 were maternal, 1 was paternal, and 2 were unknown. However, no clinical information was provided for the carrier parents. Duplications were partial duplications. The author stated that the incidence of loss-of-function variants in neurodevelopmental disorders was found to be significantly increased compared to independent cases referred for other indications. In vivo functional studies of CTNND2 missense variants in zebrafish demonstrate their loss-of-function mechanism and that CTNND2 plays a critical role in the formation and/or maintenance of synapses.
  • PUBMED: 25473103
    Hofmeister et al (2015) reported a mother and daughter who had borderline intelligence and learning problems. Karyotyping identified two apparently balanced translocations t(1;8)(p22;q24) and t(5;18)(p15;q11) in both of them. Whole-genome mate-pair sequencing and breakpoint PCR clarified the t(1;8) did not affect any coding genes, while the t(5;18) had a breakpoint within intron 9 of CTNND2 leading to a loss-of-function, 18q break affected an uncharacterized nonsignificant gene, ZSCAN30 (syn.ZNF917, ZNF397OS). Zebrafish with CTNND2 knockdown showed affected neuronal migration. Additionally, author found an exons 12-18 (out of frame) deletion (by array) in a Decipher male patient who had pronounced learning disabilities and, specifically, difficulties in reading suggestive of dyslexia, some dysmorphic features, as well as joint laxity in the fingers and a marfanoid habitus. His unaffected mother was mosaic for the microdeletion, and unaffected sibling did not carry the deletion.
  • PUBMED: 23375656
    Girirajan et al. 2013 reported a de novo 93 kb in-frame deletion of exons 4-9 in a patient with autism.
  • PUBMED: 25839933
    Belcaro et al (2015) reported a 27.6 kb deletion involving exon 14 (chr5:11,322,037-11,349,674) in a patient with delayed developmental milestones, mild intellectual disability. The patient inherited this deletion from his mother who also had delayed psychomotor development milestones, but otherwise no ID.
  • PUBMED: 31814264
    Miller et al. (2020) reported a de novo 97 kb exon 3 duplication [arr[hg19] 5p15.12(11,526,900-11,624,190)x3] in a 5-year-old male with developmental delay, behavioral problems, and dysmorphic features. Mate-pair sequencing was used to determine that the duplication is tandem and is predicted to lead to CTNND2 haploinsufficiency. Of note, this patient also had a maternally inherited 93 kb deletion [arr[hg19] 5q14.1(79,892,666-79,985,830)x1)] that was not considered to associate with the patient's phenotype, due to low pLI score of involved genes.
HI Evidence Comments:
CTNND2 maps to the Cri-du-Chat critical region. This gene has been associated with intellectual disability in Cri-du-Chat syndrome (MIM 123450)[PMID 10673328], autism spectrum disorder [PMID 15733271], cerebral palsy [PMID: 23695280] and schizophrenia [PMID 18940311]. While more recent evidence suggests that this gene is involved in neurodevelopmental phenotypes, given the non-specific phenotype and the number of inherited deletions, the current haploinsufficiency score for CTNND2 is a 1.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000005.9) (NC_000005.10)