Human Gene Module / Chromosome X / NLGN3

NLGN3neuroligin 3

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
29 / 46
Rare Variants / Common Variants
23 / 6
EAGLE Score
6.5
Moderate Learn More
Aliases
NLGN3, HNL3,  ASPGX1,  AUTSX1,  KIAA1480
Associated Syndromes
-
Chromosome Band
Xq13.1
Associated Disorders
-
Genetic Category
Rare Single Gene Mutation, Genetic Association, Functional
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.

SFARI Genomic Platforms
Reports related to NLGN3 (46 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism Jamain S , et al. (2003) Yes -
2 Negative Association Mutation screening of X-chromosomal neuroligin genes: no mutations in 196 autism probands Vincent JB , et al. (2004) Yes -
3 Negative Association NLGN3/NLGN4 gene mutations are not responsible for autism in the Quebec population Gauthier J , et al. (2004) Yes -
4 Positive Association Analysis of four neuroligin genes as candidates for autism Ylisaukko-oja T , et al. (2005) Yes -
5 Recent Recommendation The Arg473Cys-neuroligin-1 mutation modulates NMDA mediated synaptic transmission and receptor distribution in hippocampal neurons Khosravani H , et al. (2005) No -
6 Recent Recommendation Expression patterns of neurexin-1 and neuroligins in brain and retina of the chick embryo: Neuroligin-3 is absent in retina Paraoanu LE , et al. (2005) No -
7 Recent Recommendation A mutation linked with autism reveals a common mechanism of endoplasmic reticulum retention for the alpha,beta-hydrolase fold protein family De Jaco A , et al. (2006) No -
8 Negative Association Absence of coding mutations in the X-linked genes neuroligin 3 and neuroligin 4 in individuals with autism from the IMGSAC collection Blasi F , et al. (2006) Yes -
9 Recent Recommendation A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice Tabuchi K , et al. (2007) No -
10 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 functioning level Wermter AK , et al. (2008) Yes -
11 Recent Recommendation Differential expression of neuroligin genes in the nervous system of zebrafish Davey C , et al. (2010) No -
12 Recent Recommendation Neuroligin trafficking deficiencies arising from mutations in the alpha/beta-hydrolase fold protein family De Jaco A , et al. (2010) No -
13 Positive Association A sex-specific association of common variants of neuroligin genes (NLGN3 and NLGN4X) with autism spectrum disorders in a Chinese Han cohort Yu J , et al. (2011) Yes -
14 Recent Recommendation Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function Etherton M , et al. (2011) No -
15 Support Identification of Four Novel Synonymous Substitutions in the X-Linked Genes Neuroligin 3 and Neuroligin 4X in Japanese Patients with Autistic Spectrum Disorder Yanagi K , et al. (2012) Yes -
16 Support Identification of rare X-linked neuroligin variants by massively parallel sequencing in males with autism spectrum disorder Steinberg KM , et al. (2012) Yes -
17 Support Using whole-exome sequencing to identify inherited causes of autism Yu TW , et al. (2013) Yes -
18 Negative Association Lack of association between NLGN3, NLGN4, SHANK2 and SHANK3 gene variants and autism spectrum disorder in a Chinese population Liu Y , et al. (2013) Yes -
19 Recent Recommendation Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling Fldy C , et al. (2013) No -
20 Recent Recommendation Developmental regulation of GABAergic signalling in the hippocampus of neuroligin 3 R451C knock-in mice: an animal model of Autism Pizzarelli R and Cherubini E (2013) No -
21 Support Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing Jiang YH , et al. (2013) Yes -
22 Support Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders Kenny EM , et al. (2013) Yes -
23 Negative Association Variations analysis of NLGN3 and NLGN4X gene in Chinese autism patients Xu X , et al. (2014) Yes -
24 Recent Recommendation Autism-related neuroligin-3 mutation alters social behavior and spatial learning Jaramillo TC , et al. (2014) No -
25 Recent Recommendation Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors Rothwell PE , et al. (2014) No -
26 Support Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing Redin C , et al. (2014) No -
27 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
28 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) No -
29 Recent Recommendation Integrated systems analysis reveals a molecular network underlying autism spectrum disorders Li J , et al. (2015) Yes -
30 Recent Recommendation Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci Sanders SJ , et al. (2015) Yes -
31 Recent Recommendation Modulation of excitation on parvalbumin interneurons by neuroligin-3 regulates the hippocampal network Polepalli JS , et al. (2017) No -
32 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
33 Negative Association Not all neuroligin 3 and 4X missense variants lead to significant functional inactivation Xu X , et al. (2017) Yes -
34 Support Novel mutations in NLGN3 causing autism spectrum disorder and cognitive impairment Quartier A , et al. (2019) Yes -
35 Support Neuroligin 3 Regulates Dendritic Outgrowth by Modulating Akt/mTOR Signaling Xu J , et al. (2019) No -
36 Support Abnormal Social Interactions in a Drosophila Mutant of an Autism Candidate Gene: Neuroligin 3 Yost RT et al. (2020) No -
37 Support - Lai ESK et al. (2021) Yes -
38 Positive Association - Hegde R et al. (2021) Yes -
39 Support - Anstey NJ et al. (2022) No -
40 Support - Sgritta M et al. (2022) Yes -
41 Support - Gioia R et al. (2022) Yes -
42 Support - Bay H et al. (2023) Yes -
43 Support - Cirnigliaro M et al. (2023) Yes -
44 Support - Lee CYQ et al. (2023) Yes -
45 Support - Sheth F et al. (2023) Yes DD, ID
46 Support - et al. () Yes -
Rare Variants   (23)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
G>A p.(=) synonymous_variant - - - 16508939 Blasi F , et al. (2006)
A>G p.(=) synonymous_variant - - - 15274046 Vincent JB , et al. (2004)
C>G p.(=) synonymous_variant - - - 15274046 Vincent JB , et al. (2004)
- - intron_variant Unknown - Multiplex 23020841 Steinberg KM , et al. (2012)
c.1720G>A p.Asp574Asn missense_variant Familial Maternal - 38008000 et al. ()
c.607+47G>C - intron_variant Unknown - Unknown 22934180 Yanagi K , et al. (2012)
c.1276G>A p.Gly426Ser missense_variant De novo - Simplex 24570023 Xu X , et al. (2014)
c.1954A>G p.Thr652Ala missense_variant Unknown - Unknown 25549968 Li J , et al. (2015)
c.2222T>G p.Leu741Arg missense_variant De novo - Simplex 37543562 Sheth F et al. (2023)
- - 3_prime_UTR_variant Familial Maternal Multiplex 23020841 Steinberg KM , et al. (2012)
c.1698G>A p.Lys566= synonymous_variant Unknown - Unknown 22934180 Yanagi K , et al. (2012)
c.583C>T p.Arg195Trp missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.1675C>T p.Arg559Ter stop_gained Unknown - Multiplex 37506195 Cirnigliaro M et al. (2023)
c.962T>C p.Val321Ala missense_variant Familial Maternal Simplex 23352163 Yu TW , et al. (2013)
c.311del p.Pro104GlnfsTer41 frameshift_variant Unknown - Unknown 24126926 Kenny EM , et al. (2013)
c.222C>T p.Tyr74= synonymous_variant Familial - Multiplex 16077734 Ylisaukko-oja T , et al. (2005)
c.1036G>A p.Val346Met missense_variant Familial Maternal Simplex 23849776 Jiang YH , et al. (2013)
c.1954A>G p.Thr652Ala missense_variant Familial Maternal Multiplex 16508939 Blasi F , et al. (2006)
c.1411C>T p.Arg471Cys missense_variant Familial Maternal Multiplex 12669065 Jamain S , et al. (2003)
c.1480C>T p.Pro494Ser missense_variant Familial Maternal Multiplex 31184401 Quartier A , et al. (2019)
c.1228dup p.Leu410ProfsTer16 frameshift_variant Familial Maternal Simplex 28263302 C Yuen RK et al. (2017)
c.1729C>T p.Arg577Trp missense_variant Familial Maternal Extended multiplex 25167861 Redin C , et al. (2014)
c.1328G>A p.Trp443Ter stop_gained Familial Maternal Simplex 25533962 Deciphering Developmental Disorders Study (2014)
Common Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.-200-72A>G;c.-272A>G;c.-38-585A>G;c.47-72A>G;c.-116-72A>G G/A intron_variant - - - 21569590 Yu J , et al. (2011)
c.457+2188G>A;c.517+1489G>A;c.106+2188G>A;c.328+1489G>A;c.166+1489G>A A to G intron_variant - - - 21569590 Yu J , et al. (2011)
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 intron_variant - - - 21569590 Yu J , et al. (2011)
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 intron_variant - - - 21569590 Yu J , et al. (2011)
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 intron_variant - - - 21569590 Yu J , et al. (2011)
c.551T>C p.Val184Ala missense_variant - - - 35012288 Hegde R et al. (2021)
SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

1

High Confidence

See all Category 1 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

7/1/2020
1
icon
1

Score remained at 1

Description

A series of rare, deleterious variants have been reported in autism (Jamain et al., 2003 and Sanders et al., 2011; PMID: 21658581), and a gene expression study of lymphoblasts suggests reduced expression of the gene in ASD (Yasuda et al., 2011; PMID: 21615902). NLGN3 interacts with another ASD gene, NRXN1. This gene was recently 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).

1/1/2020
1
icon
1

Score remained at 1

Description

A series of rare, deleterious variants have been reported in autism (Jamain et al., 2003 and Sanders et al., 2011; PMID: 21658581), and a gene expression study of lymphoblasts suggests reduced expression of the gene in ASD (Yasuda et al., 2011; PMID: 21615902). NLGN3 interacts with another ASD gene, NRXN1. This gene was recently 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).

10/1/2019
2
icon
1

Decreased from 2 to 1

New Scoring Scheme
Description

A series of rare, deleterious variants have been reported in autism (Jamain et al., 2003 and Sanders et al., 2011; PMID: 21658581), and a gene expression study of lymphoblasts suggests reduced expression of the gene in ASD (Yasuda et al., 2011; PMID: 21615902). NLGN3 interacts with another ASD gene, NRXN1. This gene was recently 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).

Reports Added
[New Scoring Scheme]
7/1/2019
2
icon
2

Decreased from 2 to 2

Description

A series of rare, deleterious variants have been reported in autism (Jamain et al., 2003 and Sanders et al., 2011; PMID: 21658581), and a gene expression study of lymphoblasts suggests reduced expression of the gene in ASD (Yasuda et al., 2011; PMID: 21615902). NLGN3 interacts with another ASD gene, NRXN1. This gene was recently 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).

4/1/2017
2
icon
2

Decreased from 2 to 2

Description

A series of rare, deleterious variants have been reported in autism (Jamain et al., 2003 and Sanders et al., 2011; PMID: 21658581), and a gene expression study of lymphoblasts suggests reduced expression of the gene in ASD (Yasuda et al., 2011; PMID: 21615902). NLGN3 interacts with another ASD gene, NRXN1. This gene was recently 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).

Reports Added
[Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism.2003] [Mutation screening of X-chromosomal neuroligin genes: no mutations in 196 autism probands.2004] [NLGN3/NLGN4 gene mutations are not responsible for autism in the Quebec population.2004] [Analysis of four neuroligin genes as candidates for autism.2005] [Absence of coding mutations in the X-linked genes neuroligin 3 and neuroligin 4 in individuals with autism from the IMGSAC collection.2006] [No evidence for involvement of genetic variants in the X-linked neuroligin genes NLGN3 and NLGN4X in probands with autism spectrum disorder on high...2008] [A sex-specific association of common variants of neuroligin genes (NLGN3 and NLGN4X) with autism spectrum disorders in a Chinese Han cohort.2011] [Identification of Four Novel Synonymous Substitutions in the X-Linked Genes Neuroligin 3 and Neuroligin 4X in Japanese Patients with Autistic Spect...2012] [Identification of rare X-linked neuroligin variants by massively parallel sequencing in males with autism spectrum disorder.2012] [Using whole-exome sequencing to identify inherited causes of autism.2013] [Lack of association between NLGN3, NLGN4, SHANK2 and SHANK3 gene variants and autism spectrum disorder in a Chinese population.2013] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [Variations analysis of NLGN3 and NLGN4X gene in Chinese autism patients.2014] [Integrated systems analysis reveals a molecular network underlying autism spectrum disorders.2015] [Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders.2013] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [The Arg473Cys-neuroligin-1 mutation modulates NMDA mediated synaptic transmission and receptor distribution in hippocampal neurons.2005] [Expression patterns of neurexin-1 and neuroligins in brain and retina of the chick embryo: Neuroligin-3 is absent in retina.2005] [A mutation linked with autism reveals a common mechanism of endoplasmic reticulum retention for the alpha,beta-hydrolase fold protein family.2006] [A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice.2007] [Differential expression of neuroligin genes in the nervous system of zebrafish.2010] [Neuroligin trafficking deficiencies arising from mutations in the alpha/beta-hydrolase fold protein family.2010] [Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function.2011] [Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling.2013] [Developmental regulation of GABAergic signalling in the hippocampus of neuroligin 3 R451C knock-in mice: an animal model of Autism.2013] [Autism-related neuroligin-3 mutation alters social behavior and spatial learning.2014] [Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors.2014] [Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Modulation of excitation on parvalbumin interneurons by neuroligin-3 regulates the hippocampal network.2017] [Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder2017]
1/1/2017
2
icon
2

Decreased from 2 to 2

Description

A series of rare, deleterious variants have been reported in autism (Jamain et al., 2003 and Sanders et al., 2011; PMID: 21658581), and a gene expression study of lymphoblasts suggests reduced expression of the gene in ASD (Yasuda et al., 2011; PMID: 21615902). NLGN3 interacts with another ASD gene, NRXN1. This gene was recently 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).

1/1/2016
2
icon
2

Decreased from 2 to 2

Description

A series of rare, deleterious variants have been reported in autism (Jamain et al., 2003 and Sanders et al., 2011; PMID: 21658581), and a gene expression study of lymphoblasts suggests reduced expression of the gene in ASD (Yasuda et al., 2011; PMID: 21615902). NLGN3 interacts with another ASD gene, NRXN1. This gene was recently 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).

Reports Added
[Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism.2003] [Mutation screening of X-chromosomal neuroligin genes: no mutations in 196 autism probands.2004] [NLGN3/NLGN4 gene mutations are not responsible for autism in the Quebec population.2004] [Analysis of four neuroligin genes as candidates for autism.2005] [Absence of coding mutations in the X-linked genes neuroligin 3 and neuroligin 4 in individuals with autism from the IMGSAC collection.2006] [No evidence for involvement of genetic variants in the X-linked neuroligin genes NLGN3 and NLGN4X in probands with autism spectrum disorder on high...2008] [A sex-specific association of common variants of neuroligin genes (NLGN3 and NLGN4X) with autism spectrum disorders in a Chinese Han cohort.2011] [Identification of Four Novel Synonymous Substitutions in the X-Linked Genes Neuroligin 3 and Neuroligin 4X in Japanese Patients with Autistic Spect...2012] [Identification of rare X-linked neuroligin variants by massively parallel sequencing in males with autism spectrum disorder.2012] [Using whole-exome sequencing to identify inherited causes of autism.2013] [Lack of association between NLGN3, NLGN4, SHANK2 and SHANK3 gene variants and autism spectrum disorder in a Chinese population.2013] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [Variations analysis of NLGN3 and NLGN4X gene in Chinese autism patients.2014] [Integrated systems analysis reveals a molecular network underlying autism spectrum disorders.2015] [Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders.2013] [Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.2014] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [The Arg473Cys-neuroligin-1 mutation modulates NMDA mediated synaptic transmission and receptor distribution in hippocampal neurons.2005] [Expression patterns of neurexin-1 and neuroligins in brain and retina of the chick embryo: Neuroligin-3 is absent in retina.2005] [A mutation linked with autism reveals a common mechanism of endoplasmic reticulum retention for the alpha,beta-hydrolase fold protein family.2006] [A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice.2007] [Differential expression of neuroligin genes in the nervous system of zebrafish.2010] [Neuroligin trafficking deficiencies arising from mutations in the alpha/beta-hydrolase fold protein family.2010] [Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function.2011] [Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling.2013] [Developmental regulation of GABAergic signalling in the hippocampus of neuroligin 3 R451C knock-in mice: an animal model of Autism.2013] [Autism-related neuroligin-3 mutation alters social behavior and spatial learning.2014] [Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors.2014] [Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014]
10/1/2015
3
icon
2

Decreased from 3 to 2

Description

A series of rare, deleterious variants have been reported in autism (Jamain et al., 2003 and Sanders et al., 2011; PMID: 21658581), and a gene expression study of lymphoblasts suggests reduced expression of the gene in ASD (Yasuda et al., 2011; PMID: 21615902). NLGN3 interacts with another ASD gene, NRXN1. This gene was recently 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).

1/1/2015
3
icon
3

Decreased from 3 to 3

Description

A series of rare, deleterious variants have been reported in autism (Jamain et al., 2003 and Sanders et al., 2011; PMID: 21658581), and a gene expression study of lymphoblasts suggests reduced expression of the gene in ASD (Yasuda et al., 2011; PMID: 21615902). NLGN3 interacts with another ASD gene, NRXN1.

7/1/2014
No data
icon
3

Increased from No data to 3

Description

A series of rare, deleterious variants have been reported in autism (Jamain et al., 2003 and Sanders et al., 2011; PMID: 21658581), and a gene expression study of lymphoblasts suggests reduced expression of the gene in ASD (Yasuda et al., 2011; PMID: 21615902). NLGN3 interacts with another ASD gene, NRXN1.

Reports Added
[Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism.2003] [Mutation screening of X-chromosomal neuroligin genes: no mutations in 196 autism probands.2004] [NLGN3/NLGN4 gene mutations are not responsible for autism in the Quebec population.2004] [Analysis of four neuroligin genes as candidates for autism.2005] [The Arg473Cys-neuroligin-1 mutation modulates NMDA mediated synaptic transmission and receptor distribution in hippocampal neurons.2005] [Expression patterns of neurexin-1 and neuroligins in brain and retina of the chick embryo: Neuroligin-3 is absent in retina.2005] [A mutation linked with autism reveals a common mechanism of endoplasmic reticulum retention for the alpha,beta-hydrolase fold protein family.2006] [Absence of coding mutations in the X-linked genes neuroligin 3 and neuroligin 4 in individuals with autism from the IMGSAC collection.2006] [A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice.2007] [No evidence for involvement of genetic variants in the X-linked neuroligin genes NLGN3 and NLGN4X in probands with autism spectrum disorder on high...2008] [Differential expression of neuroligin genes in the nervous system of zebrafish.2010] [Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function.2011] [Neuroligin trafficking deficiencies arising from mutations in the alpha/beta-hydrolase fold protein family.2010] [A sex-specific association of common variants of neuroligin genes (NLGN3 and NLGN4X) with autism spectrum disorders in a Chinese Han cohort.2011] [Identification of Four Novel Synonymous Substitutions in the X-Linked Genes Neuroligin 3 and Neuroligin 4X in Japanese Patients with Autistic Spect...2012] [Identification of rare X-linked neuroligin variants by massively parallel sequencing in males with autism spectrum disorder.2012] [Using whole-exome sequencing to identify inherited causes of autism.2013] [Lack of association between NLGN3, NLGN4, SHANK2 and SHANK3 gene variants and autism spectrum disorder in a Chinese population.2013] [Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling.2013] [Developmental regulation of GABAergic signalling in the hippocampus of neuroligin 3 R451C knock-in mice: an animal model of Autism.2013] [Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.2013] [Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders.2013] [Variations analysis of NLGN3 and NLGN4X gene in Chinese autism patients.2014] [Autism-related neuroligin-3 mutation alters social behavior and spatial learning.2014] [Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors.2014]
4/1/2014
No data
icon
3

Increased from No data to 3

Description

A series of rare, deleterious variants have been reported in autism (Jamain et al., 2003 and Sanders et al., 2011; PMID: 21658581), and a gene expression study of lymphoblasts suggests reduced expression of the gene in ASD (Yasuda et al., 2011; PMID: 21615902). NLGN3 interacts with another ASD gene, NRXN1.

Krishnan Probability Score

Score 0.49477781949118

Ranking 3428/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
ExAC Score

Score 0.89622716838809

Ranking 3257/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.091665315890799

Ranking 62/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Larsen Cumulative Evidence Score

Score 34

Ranking 64/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Zhang D Score

Score 0.30378321260045

Ranking 2682/20870 scored genes


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The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
ACOT2 Human Protein Binding
ALPP CBS Human Protein Binding 250 P05187
C1QA Complement C1q subcomponent subunit A Human Protein Binding 712 P02745
CGB chorionic gonadotropin, beta polypeptide Human Protein Binding 1082 P01233
DPEP2 Dipeptidase 2 Human Protein Binding 64174 Q9H4A9
EBPL Emopamil-binding protein-like Human Protein Binding 84650 Q9BY08
GDF15 Growth/differentiation factor 15 Human Protein Binding 9518 Q99988
GPR175 Transmembrane protein adipocyte-associated 1 Human Protein Binding 131601 Q86W33
HID1 Protein HID1 Human Protein Binding 283987 Q8IV36
MIEN1 Migration and invasion enhancer 1 Human Protein Binding 84299 Q9BRT3
MT-CO2 Cytochrome c oxidase subunit 2 Human Protein Binding 4513 P00403
NLGN4Y Neuroligin-4, Y-linked Human Protein Binding 22829 Q8NFZ3
OR1F12 olfactory receptor, family 1, subfamily F, member 12 Human Protein Binding 442179 Q8NHA8
PLB1 Phospholipase B1, membrane-associated Human Protein Binding 151056 Q6P1J6
PLC4 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 Human Protein Binding 5332 Q15147
PSG1 Pregnancy-specific beta-1-glycoprotein 1 Human Protein Binding 5669 P11464
PSG11 pregnancy specific beta-1-glycoprotein 11 Human Protein Binding 5680 Q9UQ72
PSG3 Pregnancy-specific beta-1-glycoprotein 3 Human Protein Binding 5671 Q16557
PSG4 pregnancy specific beta-1-glycoprotein 4 Human Protein Binding 5672 Q00888
PSG5 Pregnancy-specific beta-1-glycoprotein 5 Human Protein Binding 5673 Q15238
RBM9 RNA binding protein fox-1 homolog 2 Human Protein Binding 9606 O43251
SPINT1 Kunitz-type protease inhibitor 1 Human Protein Binding 6692 O43278
TNNT3 Troponin T, fast skeletal muscle Human Protein Binding 7140 P45378
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