CUX2
Homo sapiens
Gene Name: cut like homeobox 2
Aliases: CDP2, CUTL2
Chromosome No: 12
Chromosome Band: 12q24.11-q24.12
Genetic Category: Rare single gene variant-Syndromic-Rare single gene variant/Functional
Aliases: CDP2, CUTL2
Chromosome No: 12
Chromosome Band: 12q24.11-q24.12
Genetic Category: Rare single gene variant-Syndromic-Rare single gene variant/Functional
Summary Statistics:
ASD Reports: 19
Recent Reports: 2
Annotated variants: 36
Associated CNVs: 4
Evidence score: 3
ASD Reports: 19
Recent Reports: 2
Annotated variants: 36
Associated CNVs: 4
Evidence score: 3
| Associated Disorders: |
|
Relevance to Autism
A de novo nonsense variant in the CUX2 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014. Chatron et al., 2018 identified nine patients with a recurrent de novo missense variant in the CUX2 gene (p.Glu590Lys) that presented with developmental and epileptic encephalopathy; in addition to recurrent phenotypes including epilepsy and intellectual disability, several individuals with this variant also presented with autistic features and/or motor stereotypies.
Molecular Function
This gene encodes a protein which contains three CUT domains and a homeodomain; both domains are DNA-binding motifs. The encoded protein may be a transcription factor involved in neural specification.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Synaptic, transcriptional and chromatin genes disrupted in autism.
ASD
Support
Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses
DD
Stereotypy
Support
Genetic and Phenotype Analysis of a Chinese Cohort of Infants and Children With Epilepsy
Epilepsy/seizures
Support
Genomic insights from a deeply phenotyped highly consanguineous neurodevelopmental disorders cohort
ID, epilepsy/seizures
Support
Mutational Landscape of Autism Spectrum Disorder Brain Tissue
ASD
Support
Exome sequencing improves the molecular diagnostics of paediatric unexplained neurodevelopmental disorders
ASD, DD, ID
Support
Cux2 expression regulated by Lhx2 in the upper layer neurons of the developing cortex.
Support
Reanalysis of Trio Whole-Genome Sequencing Data Doubles the Yield in Autism Spectrum Disorder: De Novo Variants Present in Half
ASD
ADHD, ID, epilepsy/seizures
Support
A recurrent de novo CUX2 missense variant associated with intellectual disability, seizures, and autism spectrum disorder.
ASD, ID, epilepsy/seizures
Support
Cux1 and Cux2 regulate dendritic branching, spine morphology, and synapses of the upper layer neurons of the cortex.
Support
Deleterious coding variation associated with autism is shared across ancestries.
ASD
Support
Cux-2 controls the proliferation of neuronal intermediate precursors of the cortical subventricular zone.
Support
CUX2 deficiency causes facilitation of excitatory synaptic transmission onto hippocampus and increased seizure susceptibility to kainate
Epilepsy/seizures
ID
Highly Cited
Expression of Cux-1 and Cux-2 in the subventricular zone and upper layers II-IV of the cerebral cortex.
Highly Cited
Dynamics of Cux2 expression suggests that an early pool of SVZ precursors is fated to become upper cortical layer neurons.
Recent Recommendation
Genomic landscape of rare variants in a Chinese autism cohort and discovery of novel risk genes.
ASD
Recent Recommendation
The epilepsy phenotypic spectrum associated with a recurrent CUX2 variant.
Epilepsy/seizures, ID
Autistic features, stereotypies
Rare
Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
GEN1011R032
inframe_insertion
c.2960_2961insCCCCCCCCCCCCCCC
p.Pro989_Ser990insProProProProPro
Unknown
Simplex
GEN1011R035
frameshift_variant
c.3754delinsTA
p.Ser1252TyrfsTer11
De novo
Simplex
Common
No Common Variants Available