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Relevance to Autism

Rare mutations in the DLGAP2 gene have been identified with autism. In separate studies, de novo duplications were found in patients with ASD (Marshall et al., 2008; Pinto et al., 2010).

Molecular Function

The encoded protein is a membrane-associated guanylate kinase localized at the post-synaptic density in neuronal cells.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Structural variation of chromosomes in autism spectrum disorder.
ASD
Support
Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders.
ASD
Support
Next-Generation Sequencing in Korean Children With Autism Spectrum Disorder and Comorbid Epilepsy
ASD
Support
Genetic diagnostic outcomes from a 10-year research programme in autism in Aotearoa New Zealand
ASD
Support
Deep exon resequencing of DLGAP2 as a candidate gene of autism spectrum disorders.
ASD
Support
Segregating patterns of copy number variations in extended autism spectrum disorder (ASD) pedigrees
ASD
Support
Genomic insights from a deeply phenotyped highly consanguineous neurodevelopmental disorders cohort
ASD, DD
Support
Functional impact of global rare copy number variation in autism spectrum disorders.
ASD
Support
Resequencing and Association Analysis of Six PSD-95-Related Genes as Possible Susceptibility Genes for Schizophrenia and Autism Spectrum Disorders.
ASD, SCZ
Support
ASD
Support
Comprehensive molecular testing in patients with high functioning autism spectrum disorder.
ASD
Support
Integrating de novo and inherited variants in 42
ASD
Support
The contribution of de novo coding mutations to autism spectrum disorder
ASD
Support
Mutational Landscape of Autism Spectrum Disorder Brain Tissue
ASD
Support
Synaptic, transcriptional and chromatin genes disrupted in autism.
ASD
Support
8p23.2-pter Microdeletions: Seven New Cases Narrowing the Candidate Region and Review of the Literature
ASD, ADHD
Highly Cited
Distinct spatiotemporal expression of SAPAP transcripts in the developing rat brain: a novel dendritically localized mRNA.
Recent Recommendation
Low load for disruptive mutations in autism genes and their biased transmission.
ASD
Recent Recommendation
Fragile X mental retardation protein regulates the levels of scaffold proteins and glutamate receptors in postsynaptic densities.
Recent Recommendation
Computational and experimental identification of novel human imprinted genes.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN066R001 
 copy_number_gain 
  
  
 De novo 
  
 Simplex 
 GEN066R002 
 copy_number_gain 
  
  
 De novo 
  
  
 GEN066R003 
 missense_variant 
 c.44C>T 
 p.Ser15Phe 
 Familial 
 Maternal 
 Simplex 
 GEN066R004 
 missense_variant 
 c.277C>A 
 p.Leu93Met 
 Familial 
 Maternal 
 Simplex 
 GEN066R005 
 missense_variant 
 c.545G>A 
 p.Gly182Asp 
 Familial 
 Paternal 
 Simplex 
 GEN066R006 
 missense_variant 
 c.574G>T 
 p.Ala192Ser 
 Unknown 
  
 Unknown 
 GEN066R007 
 missense_variant 
 c.970A>T 
 p.Arg324Trp 
 Familial 
 Paternal 
 Simplex 
 GEN066R008 
 missense_variant 
 c.1516T>C 
 p.Cys506Arg 
 Familial 
 Paternal 
 Simplex 
 GEN066R009 
 missense_variant 
 c.2392G>C 
 p.Glu798Gln 
 Familial 
 Maternal 
 Simplex 
 GEN066R010 
 missense_variant 
 c.2209G>C 
 p.Ala737Pro 
 Familial 
  
 Extended multiplex (at least one pair of ASD affec 
 GEN066R011 
 missense_variant 
 c.2216G>C 
 p.Arg739Thr 
 De novo 
  
 Simplex 
 GEN066R012 
 copy_number_loss 
  
  
 Unknown 
  
  
 GEN066R013 
 missense_variant 
 c.637A>G 
 p.Met213Val 
 De novo 
  
  
 GEN066R014 
 missense_variant 
 c.136G>A 
 p.Gly46Ser 
 Unknown 
  
  
 GEN066R015 
 missense_variant 
 c.371G>T 
 p.Arg124Leu 
 Familial 
  
  
 GEN066R016 
 missense_variant 
 c.520G>A 
 p.Asp174Asn 
 Unknown 
  
  
 GEN066R017 
 missense_variant 
 c.1225A>G 
 p.Ser409Gly 
 Unknown 
  
  
 GEN066R018 
 missense_variant 
 c.1289C>T 
 p.Ser430Phe 
 Unknown 
  
  
 GEN066R019 
 missense_variant 
 c.1810C>T 
 p.Arg604Cys 
 Familial 
 Paternal 
 Simplex 
 GEN066R020 
 missense_variant 
 c.1997G>A 
 p.Ser666Asn 
 Unknown 
  
  
 GEN066R021 
 missense_variant 
 c.2044G>A 
 p.Ala682Thr 
 Unknown 
  
  
 GEN066R022 
 missense_variant 
 c.2219C>A 
 p.Thr740Asn 
 Unknown 
  
  
 GEN066R023 
 missense_variant 
 c.2284G>A 
 p.Val762Ile 
 Unknown 
  
  
 GEN066R024 
 copy_number_gain 
  
  
 Familial 
 Paternal 
 Multiplex 
 GEN066R025 
 copy_number_gain 
  
  
 Unknown 
  
  
 GEN066R026 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN066R027 
 missense_variant 
 c.425A>C 
 p.His142Pro 
 De novo 
  
  
 GEN066R028 
 missense_variant 
 c.1330G>T 
 p.Asp444Tyr 
 De novo 
  
 Multiplex 
 GEN066R029 
 missense_variant 
 c.2710G>A 
 p.Gly904Ser 
 De novo 
  
 Multiplex 
 GEN066R030 
 missense_variant 
 c.1330G>T 
 p.Asp444Tyr 
 De novo 
  
  
 GEN066R031 
 missense_variant 
 c.2117C>T 
 p.Ala706Val 
 De novo 
  
  
 GEN066R032 
 missense_variant 
 c.2153G>A 
 p.Gly718Glu 
 Familial 
 Maternal 
  
 GEN066R033 
 missense_variant 
 c.1289G>T 
 p.Cys430Phe 
 Familial 
 Maternal 
  
 GEN066R034 
 missense_variant 
 c.232C>T 
 p.Pro78Ser 
 Familial 
 Maternal 
  
 GEN066R035 
 missense_variant 
 c.2909G>A 
 p.Arg970Gln 
 Unknown 
  
  
 GEN066R036 
 missense_variant 
 c.3089C>A 
 p.Ala1030Glu 
 Unknown 
  
  

Common

Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
 GEN066C001 
 intron_variant 
 rs2906569 
 c.-68-4A>G;c.242-4A>G 
  
 515 ASD cases and 596 controls of Han Chinese descent from Taiwan 
 Discovery 
 GEN066C002 
 missense_variant 
 rs2301963 
 c.1151C>A;c.1460C>A 
 p.Pro384Gln 
 515 ASD cases and 596 controls of Han Chinese descent from Taiwan 
 Discovery 
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
8
Deletion-Duplication
 37
 
8
Duplication
 1
 
8
Duplication
 1
 
8
Deletion
 3
 
8
Duplication
 6
 
8
Deletion
 30
 
8
Duplication
 14
 
8
Duplication
 1
 

Model Summary

Dlgap2 homozygous KO mice show no change in locomotion, no change in screen touches (exploratory behaviors), no change in reward reinforced choice behavior, increase in visual discrimination learning, increased cognitive flexibility in reversal learning paradigm, decreased cognition as measured by increased reaction times in visual discrimination and reversal learning.

References

Type
Title
Author, Year
Primary
Learning and reaction times in mouse touchscreen tests are differentially impacted by mutations in genes encoding postsynaptic interacting proteins SYNGAP1, NLGN3, DLGAP1, DLGAP2 and SHANK2
Additional
Altered odor perception in Dlgap2 mutant mice, a mouse model of autism spectrum disorder

M_DLGAP2_1_KO_HM

Model Type: Genetic LOF
Model Genotype: Homozygous
Mutation: Mutant mice with dlgap2 exons 9-10 replaced with a selection cassette in targeted mice that created a frameshift between exons 8 and 11. the targeting vector replaced 1.8kb of dlgap2 genomic dna (x14822401 to x14824243; ensemble build 69) with ires-lacz-neo cassette.
Allele Type: Knockout
Strain of Origin: C57BL/6*129S5
Genetic Background: C57BL/6*129S5
ES Cell Line: E14TG2a
Mutant ES Cell Line: E14TG2a
Model Source: University of Edinburgh

M_DLGAP2_2_KO_HT

Model Type: Genetic LOF
Model Genotype: Heterozygous
Mutation: Mutant mice with dlgap2 exons 9-10 replaced with a selection cassette in targeted mice that created a frameshift between exons 8 and 11. the targeting vector replaced 1.8kb of dlgap2 genomic dna (x14822401 to x14824243; ensemble build 69) with ires-lacz-neo cassette.
Allele Type: Knockout
Strain of Origin: C57BL/6*129S5
Genetic Background: C57BL/6*129S5
ES Cell Line: E14TG2a
Mutant ES Cell Line: E14TG2a
Model Source: University of Edinburgh

M_DLGAP2_3_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Dlgap2 knockout allele with an exon 6 deletion (MGI:6191669)
Allele Type: Knockout
Strain of Origin: 129S1/Sv
Genetic Background: C57BL/6
ES Cell Line: Not specified
Mutant ES Cell Line:
Model Source: Susan Shur-Fen Gau (National Taiwan University)

M_DLGAP2_4_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Dlgap2 knockout allele with an exon 6 deletion (MGI:6191669)
Allele Type: Knockout
Strain of Origin: 129S1/Sv
Genetic Background: C57BL/6
ES Cell Line: Not specified
Mutant ES Cell Line:
Model Source: Susan Shur-Fen Gau (National Taiwan University)

M_DLGAP2_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Reaction time: cognitive flexibility1
Decreased
Description: Decrease in response time for reward collection but no change in response latency for correct reponse or incorrect response
 Pairwise visual discrimination task
 10â??18weeks
Visual discrimination learning1
Increased
Description: Decrease in the number of trials from first presentation to 80% correct criterion; decrease in the number of correction trials to reach criterion
 Pairwise visual discrimination task
 10â??18weeks
Cognitive flexibility1
Increased
Description: Increase in percent of correct trials; no change in perseveration index
 Pairwise visual discrimination task
 10â??18weeks
Reaction time: visual discrimination1
 No change
 Pairwise visual discrimination task
 10â??18weeks
Reward reinforced choice behavior1
 No change
 Operant conditioning paradigm
 10â??18weeks
Hyperactivity1
 No change
 Home cage behavior
 10â??18weeks
 Not Reported:

M_DLGAP2_2_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Reaction time: cognitive flexibility1
Decreased
Description: Decrease in response time for reward collection but no change in response latency for correct reponse or incorrect response
 Pairwise visual discrimination task
 10â??18weeks
Visual discrimination learning1
Increased
Description: No change in the number of trials from first presentation to 80% correct criterion; decrease in the number of correction trials to reach criterion
 Pairwise visual discrimination task
 10â??18weeks
Cognitive flexibility1
 No change
 Pairwise visual discrimination task
 10â??18weeks
Reaction time: visual discrimination1
 No change
 Pairwise visual discrimination task
 10â??18weeks
Reward reinforced choice behavior1
 No change
 Operant conditioning paradigm
 10â??18weeks
Hyperactivity1
 No change
 Home cage behavior
 10â??18weeks
 Not Reported:

M_DLGAP2_3_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuronal activation: social odor1
Decreased
Description: olfactory peduncle, dorsal endopiriform nuclei, lateral olfactory tract, lateral endorhinal cortex, medial anterior bed nucleus of stria terminalis, cortical amygdaloid nucleus, medial amygdala, ventromedial hypothalamus, lateral medial preoptic nucleus, orbitofrontal cortex show reduced or ablated neuronal activation following bedding odor
Exp Paradigm: c-fos
 Immunohistochemistry
 adult
Neuronal activation: non-social odor1
Decreased
Description: medial olfactory bulb, olfactory peduncle, piriform cortex, bed nucleus of the stria terminalis, cortical amygdalar nucleus, medial amygdala, show reduced or ablated neuronal activation following banana odor
Exp Paradigm: c-fos
 Immunohistochemistry
 adult
Olfaction1
Decreased
Description: Reduced contact time when exploring food odors
 Olfactory habituation-dishabituation test
 adult
Social scent marking or recognition1
Increased
Description: Increased contact time when exploring social odors
 Olfactory habituation-dishabituation test
 adult
Anxiety1
Increased
Description: travel time in open arms decreased, no change in travel time in closed arms or center
 Elevated plus maze test
 adult
Anxiety1
Increased
Description: travel time in central zone decreased, no change in travel time in peripheral zone
 Open field test
 adult
Post-synaptic density number1
Decreased
Description: decrease in PSD-95 and no change in Shank3 expression, nonsignificant decrease in Homer expression
 Western blot
 adult
Targeted expression1
Decreased
Description: No expression of Dlgap2 protein
 Western blot
 adult
Protein expression level evidence1
Increased
Description: CamKIIb increased no change in CamKIIa levels in synaptosomes
 Western blot
 adult
General locomotor activity: ambulatory activity1
 No change
 Open field test
 adult
Neuroreceptor levels: glutamate receptors: AMPA receptors1
 No change
 Western blot
 adult
Neuroreceptor levels: glutamate receptors: mGluR1
 No change
 Western blot
 adult
Neuroreceptor levels: glutamate receptors: NMDA receptors1
 No change
 Western blot
 adult
Olfaction1
 No change
 Buried food test
 adult
 Not Reported:

M_DLGAP2_4_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Anxiety1
 No change
 Open field test
 adult
Anxiety1
 No change
 Elevated plus maze test
 adult
General locomotor activity: ambulatory activity1
 No change
 Open field test
 adult
Olfaction1
 No change
 Buried food test
 adult
Olfaction1
 No change
 Olfactory habituation-dishabituation test
 adult
Social scent marking or recognition1
 No change
 Olfactory habituation-dishabituation test
 adult
 Not Reported:





Download DLGAP2's Cytoscape file

Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
BZRAP1 benzodiazapine receptor (peripheral) associated protein 1 9256 O95153 Y2H
Corominas R , et al. 2014
DGCR6 DiGeorge syndrome critical region gene 6 8214 Q14129 Y2H
Corominas R , et al. 2014
KRT40 keratin 40, type I 125115 Q6A162 Y2H; bimolecular fluorescence complementation assay
Rolland T , et al. 2014
KRTAP4-2 keratin associated protein 4-2 85291 Q9BYR5 Y2H; bimolecular fluorescence complementation assay
Rolland T , et al. 2014
DLG4 Postsynaptic density protein 95 13385 Q62108 IP; LC-MS/MS
Frank RA , et al. 2016
Fmr1 fragile X mental retardation 1 14265 P35922 IP; qRT-PCR; WB; Northern blot
Schtt J , et al. 2009
GRIN1 glutamate receptor, ionotropic, NMDA1 (zeta 1) 14810 P35438 IP; LC-MS/MS
Frank RA , et al. 2016
Camk2A calcium/calmodulin-dependent protein kinase II alpha 25400 P11275 MS
Dosemeci A and Jaffe H 2009
Dlg4 discs, large homolog 4 (Drosophila) 29495 P31016 Y2H; GST; Surface plasmon resonance (SPR)
Takeuchi M , et al. 1997
Shank2 SH3 and multiple ankyrin repeat domains 2 171093 Q9QX74 Y2H
Boeckers TM , et al. 1999
Shank3 SH3 and multiple ankyrin repeat domains 3 59312 Q9JLU4 Y2H
Boeckers TM , et al. 1999

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