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Relevance to Autism

A SNP located in the 5'UTR of an alternative first exon of the CELF6 gene (rs2959930) associated with autism in male probands from AGRE using the transmission disequilibrium test (TDT). Screening for rare variants in the alternative first exon and exons 11-13 of the CELF6 gene in 384 male white ASD probands from AGRE identified a paternally-inherited nonsense variant in a male proband that showed incomplete penetrance with ASD. Disruption of CELF6 in mice resulted in animals exhibiting resistance to change and decreased ultrasonic vocalization as well as abnormal levels of serotonin in the brain (Dougherty et al., 2013).

Molecular Function

RNA-binding protein implicated in the regulation of pre-mRNA alternative splicing. Mediates exon inclusion and/or exclusion in pre-mRNA that are subject to tissue-specific and developmentally regulated alternative splicing.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
The disruption of Celf6, a gene identified by translational profiling of serotonergic neurons, results in autism-related behaviors.
ASD
Support
Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes
ASD
Support
Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
ASD
Support
Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders.
ASD

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN523R001 
 stop_gained 
 C>G 
  
 Familial 
 Paternal 
 Multiplex 
 GEN523R002 
 splice_site_variant 
 c.881-1G>A 
  
 Familial 
  
 Simplex 
 GEN523R003 
 stop_gained 
 c.1089C>G 
 p.Tyr363Ter 
 Familial 
 Paternal 
 Multiplex 
 GEN523R004 
 splice_site_variant 
 c.1237+2T>C 
  
 De novo 
 NA 
  

Common

Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
 GEN523C001 
 intron_variant, 5_prime_UTR_variant 
 rs2959930 
 c.346-1479C>T;c.-133C>T;c.67-1479C>T;c.-62-1479C>T;c.-195C>T;c.-24+9572C>T 
  
 3,787 individuals in 943 multiplex families from AGRE 
 Discovery 
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
15
Duplication
 66
  construct
15
Duplication
 1
 
15
Deletion-Duplication
 13
 
15
Deletion
 9
 
15
Deletion
 3
 
15
Deletion
 1
 
15
Deletion
 8
 

Model Summary

Reproducible and accurate method to profile serotonergic neurons under a variety of conditions and suggests a novel paradigm for gaining information on the etiology of psychiatric disorders.

References

Type
Title
Author, Year
Primary
The disruption of Celf6, a gene identified by translational profiling of serotonergic neurons, results in autism-related behaviors.

M_CELF6_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Targeted deletion of exon 4 of Celf6 introducing pre-mature stop codons resulting in nonsense mediated decay of mRNA.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not specified
Genetic Background: C57BL/6J
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_CELF6_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Swimming ability1
Increased
Description: Increased swim speed
Exp Paradigm: Swim speed during morris water maze test
 Morris water maze test
 3-5 months
Ultrasonic vocalization1
Decreased
Description: Decreased ultrasonic vocalizations indicated by fewer calls per recording session
Exp Paradigm: Maternal isolation test for ultrasonic vocalizations
 Monitoring ultrasonic vocalizations
 P8
Olfactory learning and memory1
Increased
Description: Increased resistance to change indicated by no effect of familiarization with odorants on hole-poking
Exp Paradigm: Modified holeboard test for resistance to change
 Hole-board test
 3-5 months
Protein expression level evidence1
Decreased
Description: Decreased celf6 signal from cells in all regions of the brain, including raphe neurons
Exp Paradigm: Celf6 expression
 Immunohistochemistry
 Unreported
Size/growth1
 No change
 General observations
 Unreported
Anxiety1
 No change
 Elevated plus maze test
 3-5 months
Spatial reference memory1
 No change
 Morris water maze test
 3-5 months
General locomotor activity1
 No change
 Open field test
 3-5 months
Grip strength1
 No change
 Ledge test
 3-5 months
Brain morphology1
 No change
 Nuclear staining
 Unreported
Hormone levels1
 No change
 Liquid chromatography-mass spectrometry (lc-ms)
 Unreported
Olfaction1
 No change
 Hole-board test
 3-5 months
Social approach1
 No change
 Three-chamber social approach test
 3-5 months
Social approach1
 No change
 Three-chamber social approach test
 3-5 months
Social interaction1
 No change
 Hole-board test
 3-5 months
 Not Reported: Circadian sleep/wake cycle, Immune response, Maternal behavior, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure

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