HELP     Sign In
Search

Relevance to Autism

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014).

Molecular Function

This gene encodes a multi-domain scaffolding protein that is required for normal development. This protein may have a role in septate junction formation, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Integrated systems analysis reveals a molecular network underlying autism spectrum disorders.
ASD
Support
Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes.
ASD
Support
Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder.
ASD
Support
Resequencing and Association Analysis of Six PSD-95-Related Genes as Possible Susceptibility Genes for Schizophrenia and Autism Spectrum Disorders.
ASD, SCZ

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN676R001 
 missense_variant 
 c.1998T>G 
 p.Asp666Glu 
 Unknown 
  
 Unknown 
 GEN676R002 
 missense_variant 
 c.2186A>T 
 p.Asn729Ile 
 Unknown 
  
  
 GEN676R003 
 missense_variant 
 c.1552G>C 
 p.Val518Leu 
 Unknown 
  
  
 GEN676R004 
 missense_variant 
 c.1470C>G 
 p.Asn606Lys 
 Unknown 
  
  
 GEN676R005 
 missense_variant 
 c.1143A>C 
 p.Glu381Asp 
 Unknown 
  
  
 GEN676R006 
 missense_variant 
 c.1030G>C 
 p.Gly344Arg 
 Unknown 
  
  
 GEN676R007 
 missense_variant 
 c.215C>T 
 p.Pro72Leu 
 Familial 
  
  
 GEN676R008 
 missense_variant 
 c.1030G>C 
 p.Gly344Arg 
 Unknown 
  
  
 GEN676R009 
 stop_gained 
 c.85C>T 
 p.Gln29Ter 
 De novo 
 NA 
 Simplex 
 GEN676R010 
 missense_variant 
 c.1249C>T 
 p.Pro417Ser 
 De novo 
 NA 
  

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
3
Duplication
 1
 
3
Duplication
 2
 
3
Duplication
 1
 
3
Duplication
 2
 
3
Duplication
 1
 
3
Duplication
 1
 
3
Deletion
 4
 
3
Duplication
 4
 
3
Deletion-Duplication
 55
 

Model Summary

dlg1 homozygous mutants are lethal compared to controls. Depending on the gene, double dlg1 heterozygotes exhibit decreased neuromuscular junction bouton numbers and altered sleep patterns. dlg1 knockdowns show a habituation deficit.

References

Type
Title
Author, Year
Primary
Synergistic interactions between Drosophila orthologues of genes spanned by de novo human CNVs support multiple-hit models of autism.
Primary
Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.

F_DLG1_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Stock acquired for positive mutation hit for dlg1 from the Bloomington Drosophila Stock Center was isogenised to the w^1118 wild type background for 7 generations.
Allele Type: Loss-of-function
Strain of Origin: w^1118
Genetic Background:
ES Cell Line:
Mutant ES Cell Line:
Model Source:

F_DLG1_2_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Stock acquired for positive mutation hit for dlg1 from the Bloomington Drosophila Stock Center was isogenised to the w^1118 wild type background for 7 generations.
Allele Type: Loss-of-function
Strain of Origin: w^1118
Genetic Background:
ES Cell Line:
Mutant ES Cell Line:
Model Source:

F_DLG1_3_KO_HT_PAK

Model Type: Genetic
Model Genotype: Heterozygous/heterozygous
Mutation: Stock acquired for positive mutation hits for dlg1 and Pak from the Bloomington Drosophila Stock Center was isogenised to the w^1118 wild type background for 7 generations. Double (trans-)heterozygotes were isogenised to each other.
Allele Type: Loss-of-function
Strain of Origin: w^1118
Genetic Background:
ES Cell Line:
Mutant ES Cell Line:
Model Source:

F_DLG1_4_KO_HT_CG5359

Model Type: Genetic
Model Genotype: Heterozygous/heterozygous
Mutation: Stock acquired for positive mutation hits for dlg1 and CG5359 from the Bloomington Drosophila Stock Center was isogenised to the w^1118 wild type background for 7 generations. Double (trans-)heterozygotes were isogenised to each other.
Allele Type: Loss-of-function
Strain of Origin: w^1118
Genetic Background:
ES Cell Line:
Mutant ES Cell Line:
Model Source:

F_DLG1_5_KO_HT_FSN

Model Type: Genetic
Model Genotype: Heterozygous/heterozygous
Mutation: Stock acquired for positive mutation hits for dlg1 and Fsn from the Bloomington Drosophila Stock Center was isogenised to the w^1118 wild type background for 7 generations. Double (trans-)heterozygotes were isogenised to each other.
Allele Type: Loss-of-function
Strain of Origin: w^1118
Genetic Background:
ES Cell Line:
Mutant ES Cell Line:
Model Source:

F_DLG1_1_KD_GAL4:UAS;RNAI-VDRC109274

Model Type: Genetic
Model Genotype: Wild type
Mutation: dlg1-Gal4 driver line expressing UAS-Dlg1-RNAi.
Allele Type: Loss-of-function
Strain of Origin: Not reported
Genetic Background: Not reported
ES Cell Line:
Mutant ES Cell Line:
Model Source:

F_DLG1_2_KD_GAL4:UAS;RNAI-VDRC41136

Model Type: Genetic
Model Genotype: Wild type
Mutation: dlg1-Gal4 driver line expressing UAS-Dlg1-RNAi.
Allele Type: Loss-of-function
Strain of Origin: Not reported
Genetic Background: Not reported
ES Cell Line:
Mutant ES Cell Line:
Model Source:

F_DLG1_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Mortality/lethality1
Increased
Description: dlg1 mutants are lethal compared to controls.
 Immunohistochemistry
 Third instar larval stage
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

F_DLG1_2_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Circadian rhythms: timing/phases of locomotor activity1
 No change
 General observations
 Adult stage
Neuroreceptor levels: glutamate receptors: ampa receptors1
 No change
 Immunohistochemistry
 Third instar larval stage
Synaptic morphology: active zone1
 No change
 Immunohistochemistry
 Third instar larval stage
Cytoskeletal organization: neuronal: axonal transport1
 No change
 Immunohistochemistry
 Third instar larval stage
 Not Reported: Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

F_DLG1_3_KO_HT_PAK

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Circadian rhythms: timing/phases of locomotor activity1
Abnormal
Description: dlg1 transheterozygous mutants lost the dark bias and displayed no significant difference between light/dark sleeping patterns compared to controls.
 General observations
 Adult stage
Synaptic morphology: active zone1
Decreased
Description: dlg1 mutants showed a significant decrease in the presynaptic active zone puncta number compared to controls.
 Immunohistochemistry
 Third instar larval stage
Cytoskeletal organization: neuronal: axonal transport1
Decreased
Description: dlg1 transheterozygous mutants showed a significant reduction in the number of neuromuscular junction boutons compared to controls.
 Immunohistochemistry
 Third instar larval stage
Neuroreceptor levels: glutamate receptors: ampa receptors1
 No change
 Immunohistochemistry
 Third instar larval stage
 Not Reported: Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

F_DLG1_4_KO_HT_CG5359

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Circadian rhythms: timing/phases of locomotor activity1
 No change
 General observations
 Adult stage
Cytoskeletal organization: neuronal: axonal transport1
 No change
 Immunohistochemistry
 Third instar larval stage
 Not Reported: Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

F_DLG1_5_KO_HT_FSN

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Circadian rhythms: timing/phases of locomotor activity1
 No change
 General observations
 Adult stage
Cytoskeletal organization: neuronal: axonal transport1
 No change
 Immunohistochemistry
 Third instar larval stage
 Not Reported: Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

F_DLG1_1_KD_GAL4:UAS;RNAI-VDRC109274

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Habituation to aversive stimuli1
Decreased
Description: When challenged in the light-off jump paradigm, the mutants showed a habituation deficit compared to controls.
Exp Paradigm: Habituation was measured in number of trials to reach no-jump criterion.
 Light-off startle jump
 adult stage
Startle response1
 No change
 Light-off startle jump
 adult stage
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

F_DLG1_2_KD_GAL4:UAS;RNAI-VDRC41136

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Habituation to aversive stimuli1
Decreased
Description: When challenged in the light-off jump paradigm, the mutants showed a habituation deficit compared to controls.
Exp Paradigm: Habituation was measured in number of trials to reach no-jump criterion.
 Light-off startle jump
 adult stage
Startle response1
 No change
 Light-off startle jump
 adult stage
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
ADGRA2 adhesion G protein-coupled receptor A2 25960 Q96PE1 IP; LC-MS/MS; IP/WB
Posokhova E , et al. 2015
ATP2B2 ATPase, Ca++ transporting, plasma membrane 2 491 Q01814 IP/WB; Y2H; GST
DeMarco SJ and Strehler EE 2001
CHD8 chromodomain helicase DNA binding protein 8 57680 Q9HCK8 CHIP-seq
Cotney J , et al. 2015
EFNB3 Ephrin-B3 1949 Q15768 IP; LC-MS/MS
Huttlin EL , et al. 2015
GJB7 Gap junction beta-7 protein 375519 Q6PEY0 IP; LC-MS/MS
Huttlin EL , et al. 2015
GPRC5B G-protein coupled receptor family C group 5 member B 51704 Q9NZH0 IP; LC-MS/MS
Huttlin EL , et al. 2015
GRIN2B glutamate receptor, ionotropic, N-methyl D-aspartate 2B 2904 Q13224 Y2H
Niethammer M , et al. 1996
KCNJ10 potassium inwardly-rectifying channel, subfamily J, member 10 3766 P78508 in silico target prediction
Horio Y , et al. 1997
LIN7C lin-7 homolog C (C. elegans) 55327 Q9NUP9 IP; LC-MS/MS
Huttlin EL , et al. 2015
MPP2 membrane protein, palmitoylated 2 (MAGUK p55 subfamily member 2) 4355 Q14168 IP; LC-MS/MS
Huttlin EL , et al. 2015
PRDM1 PR domain zinc finger protein 1 639 O75626 IP; LC-MS/MS
Huttlin EL , et al. 2015
PTEN phosphatase and tensin homolog 5728 F6KD01 Y2H; Affinity chromatography
Adey NB , et al. 2000
UBE3A ubiquitin protein ligase E3A 7337 Q05086 in vitro ubiquitination assay; WB; GST
Matsumoto Y , et al. 2006
CNTNAP2 forkhead box P2 114142 P58463 HPLC; MS/MS; IP
Chen N , et al. 2015
DLG4 Postsynaptic density protein 95 13385 Q62108 IP; LC-MS/MS
Frank RA , et al. 2016
GRIN1 glutamate receptor, ionotropic, NMDA1 (zeta 1) 14810 P35438 IP; LC-MS/MS
Frank RA , et al. 2016
PARK2 Parkinson disease (autosomal recessive, juvenile) 2, parkin 50873 Q9WVS6 FRAP
Stiffler MA , et al. 2006
GRIK2 glutamate receptor, ionotropic, kainate 2 54257 P42260 IP/WB
Garcia EP , et al. 1998

HELP
Copyright © 2017 MindSpec, Inc.