AutismKB


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Evidence Detail for NLGN4X


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Basic Information Top
Gene Symbol:NLGN4X ( ASPGX2,AUTSX2,HLNX,HNLX,KIAA1260,MGC22376,NLGN,NLGN4 )
Gene Full Name: neuroligin 4, X-linked
Band: Xp22.33
Quick LinksEntrez ID:57502; OMIM: 300427; Uniprot ID:NLGNX_HUMAN; ENSEMBL ID: ENSG00000146938
Sequences Top
>NLGN4X|57502|nucleotide
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>NLGN4X|57502|protein
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Evidence Statistic Top

Click the link of the category-specific score to view different category of evidences. The categories without any evidences are hidden by default.
Evidences Syndromic Gene GWAS Expression CNV Linkage Low Scale Association Other Studies Total
Score (No. of Studies) Yes 2 (2) 0 (0) 1 (4) 0 (0) 1 (3) 3 (7) 38 (13)
Syndromic Autism Gene Top
Abbreviations: AD, autosomal dominant; AR, autosomal recessive; ASD, autism spectrum disorder; ID, intellectual disability; XL, X linked.
InheritanceXL
OMIMMental retardation, X-linked (300495)
DescriptionNon-syndromic X-linked ID and/or ASD; both mutations and deletions have been reported
Reference(s)17910064; 12669065; 18413370; 14963808; 18231125; 18252227;
LevelLevel 3: The gene has been reported in more than one family with ASD/autistic features, but the disorder hasn't been a generally acknowledged ASD related disorder.
Low Scale Association Studies (by Ethnic Group) Top
Family Based Association Studies: 2
Case Control Based Association Studies: 1
Reference Population #SNPs/ #VNTRs ASD Cases Normal Controls Result
#Subjects
(% Women)
ADI-R ADOS Diagnosis Age
(range)
IQ #Subjects
(% Women)
Age
(range)
CAUCASIAN
Kelemenova, 2010_1 Slovakia 1 (detail) 90
(0.00%)
ASD -
-
- 85
(-)
-
-
Genome-Wide Association Studies(By Ethnic Group) Top
Family Based Association Studies: 1
Reference Stage #SNPs/ #VNTRs #Families Affecteds Result
#Subjects
(% Women)
ADI-R ADOS Diagnosis Age
(range)
IQ
(range)
CAUCASIAN
Wang, 2009_1 Discovery 1 (detail) 780 1299
(-)
ASD -
-
-
-
Case Control Based Association Studies: 1
Reference Stage #SNPs/ #VNTRs ASD Cases Normal Controls Result
#Subjects
(% Women)
ADI-R ADOS Diagnosis Age
(range)
IQ #Subjects
(% Women)
Age
(range)
CAUCASIAN
Wang, 2009_2 Discovery 1 (detail) 1204
(-)
ASD 10.3±6.6
-
10.9±6.7 6491
(-)
8.8±5.4
-
Other Low Scale Gene Studies Top
Reference Orangnism Tissue ADI-R ADOS Diagnosis Evidence Level Result
Jamain, 2003_1 human -ASD genetics: mutation screen
  • Subjects: 2
  • Normal Controls: 350 (250 female, 100 male)
  • Methods: -
  • Evidence Details: A frameshift mutation (1186insT) in NLGN4 is found in one Swedish family with two affected brothers, one with typical autism and the other with Asperger syndrome.
Laumonnier, 2004_1 human ---AD genetics: mutation screen
  • Subjects: 1 large French family
  • Normal Controls: -
  • Methods: mutation screen
  • Evidence Details: A large French family including members affected by nonspecific X-linked mental retardation, with or without autism or pervasive developmental disorder in affected male patients, has been found to have a 2-base-pair deletion in the Neuroligin 4 gene (NLGN4) located at Xp22.33. This mutation leads to a premature stop codon in the middle of the sequence of the normal protein and is thought to suppress the transmembrane domain and sequences important for the dimerization of neuroligins that are required for proper cell-cell interaction through binding to beta-neurexins.
Talebizadeh, 2004_1 human blood--ASD genetics: mutation screen
  • Subjects: 67 (64 autism and 3 Asperger Syndrome, 41 female, 26 male)
  • Normal Controls: -
  • Methods: PCR, sequence
  • Evidence Details: The reported mutations in the two neuroligin genes were not detected in our group of individuals with ASD (American males and females), suggesting that these specific gene mutations are not common or found in a low frequency in the autism population
Vincent, 2004_1 human ---AD genetics: mutation screen
  • Subjects: 196
  • Normal Controls: -
  • Methods: -
  • Evidence Details: Our own study, screening a larger sample of 196 autism probands, failed to identify any mutations that would affect the coding regions of these genes. Our findings suggest that mutations in these two genes are infrequent in autism.
Gauthier, 2005_1 human ---AD genetics: mutation screen
  • Subjects: 96
  • Normal Controls: -
  • Methods: mutation screen
  • Evidence Details: NLGN3/NLGN4 gene mutations are not responsible for autism in the Quebec population.
Yan, 2005_1 human -ASD genetics: mutation screen
  • Subjects: 148
  • Normal Controls: 336
  • Methods: DOVAM-S (Detection of Virtually All Mutations-SSCP), direct sequencing
  • Evidence Details: G99S and K378R were found in unrelated Portuguese patients. V403M and R704C were found in unrelated Midwest patients.
Talebizadeh, 2006_1 human lymphoblastoid cell--AD function: alternative splice
  • Subjects: 10 female
  • Normal Controls: -
  • Methods: -
  • Evidence Details: The NLGN3 transcript was present in two isoforms (with and without exon 7) in nine of 10 autistic females and in 30 non-autistic subjects, including parents of the autistic female having only the complete transcript with exon 7, and from the whole brain of a control.
Lawson-Yuen, 2008_1 human ---ASD genetics: mutation screen
  • Subjects: 1 family
  • Normal Controls: -
  • Methods: mutation screen
  • Evidence Details: We describe here a family with a wide variation in neuropsychiatric illness associated with a deletion of exons 4, 5, and 6 of NLGN4.
Zhang, 2009_1 human bloodautism case report, protein expression
  • Subjects: 2 brothers (SS, 5 years; TS, 3 years)
  • Normal Controls: -
  • Methods: 500K SNP microarray
  • Evidence Details: we describe two brothers with classical ASD who carry a single amino acid substitution in NL4 (R87W). This substitution was absent from the brothers' asymptomatic parents, suggesting that it arose in the maternal germline. R87 is conserved in all NL isoforms, and the R87W substitution is not observed in control individuals.
Zhang, 2009_2 human HEK293 and COS cells--- protein expression, RNA expression
  • Subjects: -
  • Normal Controls: -
  • Methods: Immunocytochemistry,synapse formation assay,Membrane Biotinylation Assay,Glycosylation assay
  • Evidence Details: At the protein level, the R87W-substitution impaired glycosylation processing of NL4 expressed in HEK293 and COS cells, destabilized NL4, caused NL4 retention in the endoplasmic reticulum in non-neuronal cells and neurons, and blocked NL4 transport to the cell-surface.
Pampanos, 2009_1 human blood--autism genetics: mutation screen
  • Subjects: 169
  • Normal Controls: -
  • Methods: -
  • Evidence Details: In the preliminary study of specific exons of NLGN3 and NLGN4 genes, we identified the p.K378R substitution (c.1597 A > G) in exon 5 of the NLGN4 gene in a patient who was found to have mild autism and normal IQ at 3 years of age.
Daoud, 2009_1 human bloodautism genetics: mutation screen
  • Subjects: 96 (80 male and 16 female)
  • Normal Controls: -
  • Methods: PCR, sequencing of the entire coding sequence and the regulatory sequences
  • Evidence Details: We identified a de novo 1 base pair (?335G>A) substitution located in the promoter region in a patient with autism and nonsyndromic profound MR.
Daoud, 2009_2 human lymphoblastoid cell linesautism RNA expression
  • Subjects: 1
  • Normal Controls: 11 (6 female and 5 male)
  • Methods: Real-Time Reverse Transcription PCR, Luciferase assay
  • Evidence Details: The variation (?335G>A) is associated with an increased level of the NLGN4X transcript in the patient compared with male control subjects as well as his father by real time RT-PCR. Luciferase assay found a significant increase (twofold) of the luciferase gene expression under the control of the mutated NLGN4X promoter (p<0.05).
Daoud, 2009_3 human adult brain--- RNA regulation
  • Subjects: -
  • Normal Controls: -
  • Methods: Electrophoretic Mobility Shift Assay (EMSA)
  • Evidence Details: A different migration profile when mutated probe (?335G>A) was used, suggesting that DNA/TF complexes are altered in presence of the mutation.
Piton, 2010_1 human bloodASD genetics: mutation screen
  • Subjects: 142( 122 males and 20 females)
  • Normal Controls: -
  • Methods: direct sequencing
  • Evidence Details: Exonic variants identified during the the screening of the 171 X-linked synapic genes
Yasuda, 2011_1 human lymphoblastoid cellsASD mRNA expression level
  • Subjects: 35
  • Normal Controls: 35
  • Methods: RT-PCR
  • Evidence Details: Expression levels of NLGN4 mRNA were not quantitatively measurable in lymphoblastoid cells
Large Scale Expression Studies Top
CNV Studies Top
CNV Name Chr Band Gain/Loss Number of CNVs Evidence Type Reference
Case Control
AutCNV0000161 X Xp22.33-22.31 loss 1 - Denovo CNVs; Marshall, 2008
AutCNV0000299 X Xp22 loss 1 - Denovo CNVs; Thomas, 1999
AutCNV0000300 X Xp22 loss 1 - Denovo CNVs; Thomas, 1999
AutCNV0000301 X Xp22 loss 1 - Denovo CNVs; Thomas, 1999
AutCNV0000713 X Xp11.2-p22.33 gain 1 - CNVs Only Present In Patients; Edens, 2011
AutCNV0004398 X Xp22.32-p22.33 loss 1 - CNVs Only Present In Patients; Sanders, 2011
Linkage Studies Top

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Syndromic Genes

Non-syndromic Genes

AutismKB Statistics

  • Studies: 616
  • Genes: 3,075
  • SNPs/VNTRs: 3,386
  • CNVs: 4,617
  • Linkage Regions: 158
  • Last Update: 05/25/2012
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