NLGN3
Homo sapiens
Gene Name: neuroligin 3
Aliases: HNL3, ASPGX1, AUTSX1, KIAA1480
Chromosome No: X
Chromosome Band: Xq13.1
Genetic Category: Rare Single Gene variant-Rare Single Gene variant, Genetic Association--Rare Single Gene variant,Genetic Association-Rare single gene variant/genetic association-Functional-Genetic association-Rare single gene variant/Functional
Aliases: HNL3, ASPGX1, AUTSX1, KIAA1480
Chromosome No: X
Chromosome Band: Xq13.1
Genetic Category: Rare Single Gene variant-Rare Single Gene variant, Genetic Association--Rare Single Gene variant,Genetic Association-Rare single gene variant/genetic association-Functional-Genetic association-Rare single gene variant/Functional
Summary Statistics:
ASD Reports: 49
Recent Reports: 14
Annotated variants: 37
Associated CNVs: 10
Evidence score: 3
ASD Reports: 49
Recent Reports: 14
Annotated variants: 37
Associated CNVs: 10
Evidence score: 3
| Associated Disorders: |
|
Relevance to Autism
Studies have found rare single gene variations in the NLGN3 gene in autism. However, other studies claimed to find no rare variations in the NLGN3 gene in autism patients, although one of these found several silent variations. One study (Ylisaukko-oja et al., 2005) found a genetic association between an NLGN3 variant and autism in a sample of Finnish autism families, and another study (Yu et al., 2011) found a genetic association between an NLGN3 variant and autism in the Chinese Han population. This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.
Molecular Function
This gene encodes a member of a family of neuronal cell-adhesion proteins located at the postsynaptic side of the synapse. Members of this family may act as splice site-specific ligands for beta-neurexins and may be involved in the formation and remodeling of central nervous system synapses.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism.
ASD
Positive Association
Genetic analysis of the postsynaptic transmembrane X-linked neuroligin 3 gene in autism
ASD
Positive Association
A sex-specific association of common variants of neuroligin genes (NLGN3 and NLGN4X) with autism spectrum disorders in a Chinese Han cohort.
ASD
Positive Association
Analysis of four neuroligin genes as candidates for autism.
ASD
Negative Association
Not all neuroligin 3 and 4X missense variants lead to significant functional inactivation.
ASD
Negative Association
Variations analysis of NLGN3 and NLGN4X gene in Chinese autism patients.
ASD
Negative Association
Lack of association between NLGN3, NLGN4, SHANK2 and SHANK3 gene variants and autism spectrum disorder in a Chinese population.
ASD
Negative Association
No evidence for involvement of genetic variants in the X-linked neuroligin genes NLGN3 and NLGN4X in probands with autism spectrum disorder on high...
ASD
Negative Association
Absence of coding mutations in the X-linked genes neuroligin 3 and neuroligin 4 in individuals with autism from the IMGSAC collection.
ASD
Negative Association
NLGN3/NLGN4 gene mutations are not responsible for autism in the Quebec population.
ASD
Negative Association
Mutation screening of X-chromosomal neuroligin genes: no mutations in 196 autism probands.
ASD
Support
An Autism-Associated Neuroligin-3 Mutation Affects Developmental Synapse Elimination in the Cerebellum
ASD
Support
Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.
ID
Support
Abnormal Social Interactions in a Drosophila Mutant of an Autism Candidate Gene: Neuroligin 3
Support
Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders.
ASD, SCZ
Support
Neuroligin 3 Regulates Dendritic Outgrowth by Modulating Akt/mTOR Signaling.
Support
Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.
ASD
Support
Novel mutations in NLGN3 causing autism spectrum disorder and cognitive impairment.
ASD or autistic behavior, ID
Support
Using whole-exome sequencing to identify inherited causes of autism.
ASD
Support
Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder
ASD
Support
Identification of rare X-linked neuroligin variants by massively parallel sequencing in males with autism spectrum disorder.
ASD
Support
Large-scale discovery of novel genetic causes of developmental disorders.
Specific learning disability
Support
Imbalance of flight-freeze responses and their cellular correlates in the Nlgn3 -/y rat model of autism
Support
Identification of Four Novel Synonymous Substitutions in the X-Linked Genes Neuroligin 3 and Neuroligin 4X in Japanese Patients with Autistic Spect...
ASD
Support
The contribution of de novo coding mutations to autism spectrum disorder
ASD
Recent Recommendation
Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling.
Recent Recommendation
Modulation of excitation on parvalbumin interneurons by neuroligin-3 regulates the hippocampal network.
Recent Recommendation
The Arg473Cys-neuroligin-1 mutation modulates NMDA mediated synaptic transmission and receptor distribution in hippocampal neurons.
Recent Recommendation
Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function.
Recent Recommendation
Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci.
ASD
Recent Recommendation
Neuroligin trafficking deficiencies arising from mutations in the alpha/beta-hydrolase fold protein family.
Recent Recommendation
Integrated systems analysis reveals a molecular network underlying autism spectrum disorders.
ASD
Recent Recommendation
Differential expression of neuroligin genes in the nervous system of zebrafish.
Recent Recommendation
Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors.
Recent Recommendation
A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice.
Recent Recommendation
Autism-related neuroligin-3 mutation alters social behavior and spatial learning.
Recent Recommendation
A mutation linked with autism reveals a common mechanism of endoplasmic reticulum retention for the alpha,beta-hydrolase fold protein family.
Recent Recommendation
Developmental regulation of GABAergic signalling in the hippocampus of neuroligin 3 R451C knock-in mice: an animal model of Autism.
Recent Recommendation
Expression patterns of neurexin-1 and neuroligins in brain and retina of the chick embryo: Neuroligin-3 is absent in retina.
Rare
Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
GEN171R001
missense_variant
c.1411C>T
p.Arg471Cys
Familial
Maternal
Multiplex
GEN171R023
stop_gained
c.1328G>A
p.Trp443Ter
Familial
Maternal
Simplex
GEN171R024
missense_variant
c.1729C>T
p.Arg577Trp
Familial
Maternal
Extended multiplex
GEN171R026
frameshift_variant
c.1228dup
p.Leu410ProfsTer16
Familial
Maternal
Simplex
GEN171R027
frameshift_variant
c.1228dup
p.Leu410ProfsTer16
Familial
Maternal
Simplex
GEN171R028
missense_variant
c.1480C>T
p.Pro494Ser
Familial
Maternal
Multiplex
Common
Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
GEN171C001
intron_variant
rs11795613
c.-200-72A>G;c.-272A>G;c.-38-585A>G;c.47-72A>G;c.-116-72A>G
G/A
Chinese Han
Discovery
GEN171C002
intron_variant
rs4844285
c.457+2188G>A;c.517+1489G>A;c.106+2188G>A;c.328+1489G>A;c.166+1489G>A
A to G
Chinese Han
Discovery
GEN171C003
intron_variant
rs4844286
c.458-3490T>G;c.458-1753T>G;c.518-1753T>G;c.107-1753T>G;c.329-1753T>G;c.167-1753T>G
G to T
Chinese Han
Discovery
GEN171C004
intron_variant
rs5981079
c.458-2809T>C;c.458-1072T>C;c.518-1072T>C;c.107-1072T>C;c.329-1072T>C;c.167-1072T>C
C to T
Chinese Han
Discovery
GEN171C005
intron_variant
rs7051529
c.458-860A>G;c.517+818A>G;c.577+818A>G;c.166+818A>G;c.388+818A>G;c.226+818A>G
G/A
Chinese Han
Discovery
GEN171C006
missense_variant
c.551T>C
p.Val184Ala
108 ASD probands from the North Karnataka region of India and 150 age-, sex-, and ethnicity-matched healthy controls
Discovery
