NLGN3neuroligin 3
Autism Reports / Total Reports
34 / 53Rare Variants / Common Variants
23 / 6Aliases
NLGN3, HNL3, ASPGX1, AUTSX1, KIAA1480Associated Syndromes
-Chromosome Band
Xq13.1Associated Disorders
-Genetic Category
Rare Single Gene Mutation, Genetic Association, FunctionalRelevance 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
SFARI Genomic Platforms
Reports related to NLGN3 (53 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 | - | Lucie Sedlackova et al. (2024) | Yes | - |
| 47 | Support | - | Bekir Altas et al. () | No | - |
| 48 | Support | - | Suzanne Hosie et al. (2024) | Yes | - |
| 49 | Support | - | Lin-Yu Li et al. (2024) | Yes | - |
| 50 | Support | - | Mara H Cowen et al. (2024) | No | - |
| 51 | Support | - | Liming Qin et al. () | Yes | - |
| 52 | Support | - | Haiyan Sun et al. () | Yes | - |
| 53 | Support | - | Xin-Yu Cai 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.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.1720G>A | p.Asp574Asn | missense_variant | Familial | Maternal | - | 38008000 | Lucie Sedlackova et al. (2024) | |
| 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
High Confidence
Score Delta: Score remained at 1
criteria met
See SFARI Gene'scoring criteriaWe 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
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
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
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
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
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
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
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
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
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.
Reports Added
[Integrated systems analysis reveals a molecular network underlying autism spectrum disorders.2015] [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]7/1/2014
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
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
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ExAC Score
Score 0.89622716838809
Ranking 3257/18225 scored genes
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Sanders TADA Score
Score 0.091665315890799
Ranking 62/18665 scored genes
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Larsen Cumulative Evidence Score
Score 34
Ranking 64/461 scored genes
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Zhang D Score
Score 0.30378321260045
Ranking 2682/20870 scored genes
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External PIN Data
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
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 |