Developmental Brain Disorder Gene Database

LoF Variant Gene

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Tier

1

CASK

HGNC:1497 (protein-coding gene)

calcium/calmodulin dependent serine protein kinase

Unique Cases:
49
Disorders:
ID, ASD, EP, CP
Last Updated:
January 24, 2024

Summary
Cases
Publications
External

Gene Summary:

DBD Genes Classification
CASK 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
Multidomain scaffolding Mg(2+)-independent protein kinase that catalyzes the phosphotransfer from ATP to proteins such as NRXN1, and plays a role in synaptic transmembrane protein anchoring and ion channel trafficking (PubMed:18423203). Contributes to neural development and regulation of gene expression via interaction with the transcription factor TBR1. Binds to cell-surface proteins, including amyloid precursor protein, neurexins and syndecans. May mediate a link between the extracellular matr... (Source: Uniprot)
Previous symbols
TNRC8
Alias symbols
LIN2, CAGH39, FGS4
Chromosomal Location
Xp11.4
Genomic Coordinates
GRCh37:chrX:41374187-41782287
GRCh38:chrX:41514934-41923554
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

3.08

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.07

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

No Classification

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Definitive8 Supportive2 Strong2

Publications:

Na JH et. al., Targeted gene panel sequencing in early infantile onset developmental and epileptic encephalopathy., Brain Dev, 2020
Alsubaie L et. al., Genomic testing and counseling: The contribution of next-generation sequencing to epilepsy genetics., Ann Hum Genet, 2020
Hayashi S et. al., Comprehensive investigation of CASK mutations and other genetic etiologies in 41 patients with intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH)., PLoS One, 2017
Snoeijen-Schouwenaars FM et. al., Diagnostic exome sequencing in 100 consecutive patients with both epilepsy and intellectual disability., Epilepsia, 2019
Moog U et. al., Phenotypic spectrum associated with CASK loss-of-function mutations., J Med Genet, 2011
Michaud JL et. al., The genetic landscape of infantile spasms., Hum Mol Genet, 2014
Rump P et. al., Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly., BMC Med Genomics, 2016
Helbig KL et. al., Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy., Genet Med, 2016
Lee H et. al., Clinical exome sequencing for genetic identification of rare Mendelian disorders., JAMA, 2014
Kodera H et. al., Targeted capture and sequencing for detection of mutations causing early onset epileptic encephalopathy., Epilepsia, 2013
Deciphering Developmental Disorders Study. et. al., Large-scale discovery of novel genetic causes of developmental disorders., Nature, 2015
Stojanovic JR et. al., Diagnostic and Clinical Utility of Clinical Exome Sequencing in Children With Moderate and Severe Global Developmental Delay / Intellectual Disability., J Child Neurol, 2020
Burglen L et. al., Spectrum of pontocerebellar hypoplasia in 13 girls and boys with CASK mutations: confirmation of a recognizable phenotype and first description of a male mosaic patient., Orphanet J Rare Dis, 2012
Hesse AN et. al., Retrospective genotype-phenotype analysis in a 305 patient cohort referred for testing of a targeted epilepsy panel., Epilepsy Res, 2018
Ko A et. al., Targeted gene panel and genotype-phenotype correlation in children with developmental and epileptic encephalopathy., Epilepsy Res, 2018
Guo YX et. al., Whole-Exome Sequencing for Identifying Genetic Causes of Intellectual Developmental Disorders., Int J Gen Med, 2021
Moreno-De-Luca A et. al., Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy., JAMA, 2021

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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