Developmental Brain Disorder Gene Database

LoF Variant Gene

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Tier

1

CTNNB1

HGNC:2514 (protein-coding gene)

catenin beta 1

Unique Cases:
68
Disorders:
ID, ASD, EP, ADHD, SCZ, CP
Last Updated:
November 4, 2024

Summary
Cases
Publications
External

Gene Summary:

DBD Genes Classification
CTNNB1 is a High Confidence candidate gene classified as Tier 1. Tier 1 genes have three or more de novo pathogenic loss-of-function variants.
Gene Function
Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938). In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N- terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957... (Source: Uniprot)
Previous symbols
CTNNB
Alias symbols
beta-catenin, armadillo
Chromosomal Location
3p22.1
Genomic Coordinates
GRCh37:chr3:41240915-41281944
GRCh38:chr3:41199422-41240445
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Attention Deficit Hyperactivity Disorder, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

0.18

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.13

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

Definitive

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Strong4 Definitive2 Moderate1 Supportive2

Publications:

Wirth T et. al., Increased diagnostic yield in complex dystonia through exome sequencing., Parkinsonism Relat Disord, 2020
Wang T et. al., Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders., Nat Commun, 2020
Tucci V et. al., Dominant β-catenin mutations cause intellectual disability with recognizable syndromic features., J Clin Invest, 2014
Thevenon J et. al., Diagnostic odyssey in severe neurodevelopmental disorders: toward clinical whole-exome sequencing as a first-line diagnostic test., Clin Genet, 2016
Dillon OJ et. al., Exome sequencing has higher diagnostic yield compared to simulated disease-specific panels in children with suspected monogenic disorders., Eur J Hum Genet, 2018
Trujillano D et. al., Clinical exome sequencing: results from 2819 samples reflecting 1000 families., Eur J Hum Genet, 2017
Deciphering Developmental Disorders Study. et. al., Large-scale discovery of novel genetic causes of developmental disorders., Nature, 2015
Coe BP et. al., Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity., Nat Genet, 2019
Kuechler A et. al., De novo mutations in beta-catenin (CTNNB1) appear to be a frequent cause of intellectual disability: expanding the mutational and clinical spectrum., Hum Genet, 2015
Wang H et. al., Identification of a novel splice mutation in CTNNB1 gene in a Chinese family with both severe intellectual disability and serious visual defects., Neurol Sci, 2019
Beighley JS et. al., Clinical Phenotypes of Carriers of Mutations in CHD8 or Its Conserved Target Genes., Biol Psychiatry, 2020
de Ligt J et. al., Diagnostic exome sequencing in persons with severe intellectual disability., N Engl J Med, 2012
Grozeva D et. al., Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability., Hum Mutat, 2015
Winczewska-Wiktor A et. al., A de novo CTNNB1 nonsense mutation associated with syndromic atypical hyperekplexia, microcephaly and intellectual disability: a case report., BMC Neurol, 2016
Wang Q et. al., Effect of Damaging Rare Mutations in Synapse-Related Gene Sets on Response to Short-term Antipsychotic Medication in Chinese Patients With Schizophrenia: A Randomized Clinical Trial., JAMA Psychiatry, 2018
Percy AK et. al., When Rett syndrome is due to genes other than MECP2., Transl Sci Rare Dis, 2018
Yechieli M et. al., Diagnostic yield of chromosomal microarray and trio whole exome sequencing in cryptogenic cerebral palsy., J Med Genet, 2022
Li N et. al., In-depth analysis reveals complex molecular aetiology in a cohort of idiopathic cerebral palsy., Brain, 2022
Takezawa Y et. al., Genomic analysis identifies masqueraders of full-term cerebral palsy., Ann Clin Transl Neurol, 2018
Zech M et. al., Monogenic variants in dystonia: an exome-wide sequencing study., Lancet Neurol, 2020
Lee HF et. al., Diagnostic yield and treatment impact of whole-genome sequencing in paediatric neurological disorders., Dev Med Child Neurol, 2021
Jin SC et. al., Mutations disrupting neuritogenesis genes confer risk for cerebral palsy., Nat Genet, 2020
Moreno-De-Luca A et. al., Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy., JAMA, 2021
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NCBI: Gene

Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
NCBI: Gene

Gene Reviews

An international point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.
Gene Reviews

DECIPHER

DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient.
DECIPHER

SFARI

SFARI Gene is an evolving online database designed to permit quick entrée into the genetics of autism, and to help researchers track the ever-expanding genetic risk factors that emerge in the literature.
SFARI

ClinGen

ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.
ClinGen

GenCC

The GenCC DB provides information pertaining to the validity of gene-disease relationships, with a current focus on Mendelian diseases.
GenCC

gnomAD

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects, and making summary data available for the wider scientific community.
gnomAD
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