HELP     Sign In
Search

Relevance to Autism

Genetic association has been found between the FEZF2 gene and autism in two large cohorts (AGRE and ACC) of European ancestry and replicated in two other cohorts (CAP and CART) (Wang et al., 2009). In addition, a rare mutation in the FEZF2 gene has been identified in an individual with ASD (Sanders et al., 2012). A de novo loss-of-function variant in FEZF2 was identified in an ASD proband from the SPARK cohort in Feliciano et al., 2019; in the same report, a meta-analysis of de novo variants in 4773 published ASD trios and 465 SPARK trios using TADA identified FEZF2 as an ASD candidate gene with a q-value 0.1.

Molecular Function

Regulation of transcription

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Common genetic variants on 5p14.1 associate with autism spectrum disorders.
ASD
Positive Association
A genome-wide association study of autism incorporating autism diagnostic interview-revised, autism diagnostic observation schedule, and social res...
ASD
Support
Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield.
DD, autistic behavior
Support
De novo mutations revealed by whole-exome sequencing are strongly associated with autism.
ASD
Highly Cited
Fezl is required for the birth and specification of corticospinal motor neurons.
Highly Cited
Zinc finger protein too few controls the development of monoaminergic neurons.
Recent Recommendation
Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes.
ASD
Recent Recommendation
SOX5 postmitotically regulates migration, postmigratory differentiation, and projections of subplate and deep-layer neocortical neurons.
Recent Recommendation
The Fezf2-Ctip2 genetic pathway regulates the fate choice of subcortical projection neurons in the developing cerebral cortex.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN090R001 
 missense_variant 
 c.1030C>T 
 p.Arg344Cys 
 De novo 
 NA 
 Simplex 
 GEN090R002a 
 inframe_deletion 
 c.710_721del 
 p.Arg237_Ala240del 
 Familial 
 Both parents 
 Multiplex 
 GEN090R003 
 frameshift_variant 
 c.1193del 
 p.Phe398SerfsTer7 
 De novo 
 NA 
  

Common

Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
 GEN090C001 
 2KB_upstream_variant 
 rs3755827 
 c.-1476A>G 
 C to T 
 US and European 
 Discovery 
 GEN090C002 
 2KB_upstream_variant 
 rs3755827 
 c.-1476A>G 
  
 Discovery cohort: 2165 participants from AGRE 
 Discovery 
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
3
Deletion
 1
 
3
Deletion
 7
 
3
Deletion
 1
 
3
Deletion
 1
 

Model Summary

Possible link between the transcriptional regulation of forebrain development and hyperactive behavio.

References

Type
Title
Author, Year
Primary
Zinc finger gene fez-like functions in the formation of subplate neurons and thalamocortical axons.

M_FEZF2_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Homologous recombination of exons containing the coding region (amino acids 27-455) of Fezf2 gene.
Allele Type: Targeted (Knock Out)
Strain of Origin: C57BL/6
Genetic Background: Not Specified
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_FEZF2_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity1
Increased
Description: Increased motor activity; Hyperactive
Exp Paradigm: Open Field test
 Open field test
 Unreported
Brain anatomy1
Decreased
Description: Decreased size of internal capsule; Irregular boundary between the cortical plate and intermediate zone; Decreased intermediate zone
Exp Paradigm: Histological analysis
 Histology
 E17.5
Brain anatomy1
Abnormal
Description: Decreased number of subplate neuron stainings in dorsal and lateral cortex; decreased chondroitin sulfate proteoglycan (CSPG)-rich subplate region; No Change in layer formation of cortex
Exp Paradigm: Anti-GAP43 and anti-chondroiton immunohistochemical analysis of coronal sections; Nissl and hematoxylin-eosin staining
 Immunohistochemistry
 E11.5-16.5
Brain anatomy1
Decreased
Description: Decreased number of L-1 positive thalamocortical axons (TCA) extending to cortex; Abberant location in telencephalon
Exp Paradigm: Immunohistochemical Analysis of coronal sections with an anti-L1 antibody and an anti-TAG1 antibody
 Immunohistochemistry
 E16.5
Size/growth1
Decreased
Description: Decreased size
Exp Paradigm: General observations
 General observations
 3 weeks
Mortality/lethality1
Increased
Description: Increased lethality
Exp Paradigm: General observations
 General observations
 4 weeks
Developmental trajectory1
Abnormal
Description: Abnormal diet; Decreased lethality on powdered food diet
Exp Paradigm: General observations
 General observations
 Unreported
Digestive system development1
 No change
 Histology
 Unreported
General characteristics1
 No change
 General observations
 0-3 weeks
Brain morphology1
 No change
 Immunohistochemistry
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neurophysiology, Physiological parameters, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
FOXG1 forkhead box G1 15228 Q60987 ChIP; ChIP-Seq
Eckler MJ , et al. 2014
HOXA1 homeobox A1 15394 P09022 Gene microarray
Makki N and Capecchi MR 2011
SOX5 SRY-box containing gene 5 20678 P35710 ChIP; ChIP-Seq
Eckler MJ , et al. 2014
Tbr1 T-box brain gene 1 21375 Q64336 ChIP
Han W , et al. 2011

HELP
Copyright © 2017 MindSpec, Inc.