NLGN3 neuroligin 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NLGN3provided by HGNC
Official Full Name: neuroligin 3provided by HGNC
Primary source: HGNC:HGNC:14289
See related: Ensembl:ENSG00000196338 MIM:300336; AllianceGenome:HGNC:14289
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HNL3
Summary: This gene encodes a member of a family of neuronal cell surface proteins. 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. Mutations in this gene may be associated with autism and Asperger syndrome. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Oct 2009]
Expression: Biased expression in brain (RPKM 14.8), adrenal (RPKM 2.6) and 4 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: Xq13.1

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (71144841..71175307)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (69578926..69609395)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (70364691..70391051)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Analyses of the autism-associated neuroligin-3 R451C mutation in human neurons reveal a gain-of-function synaptic mechanism.
Title: Analyses of the autism-associated neuroligin-3 R451C mutation in human neurons reveal a gain-of-function synaptic mechanism.
Stabilization of KPNB1 by deubiquitinase USP7 promotes glioblastoma progression through the YBX1-NLGN3 axis.
Title: Stabilization of KPNB1 by deubiquitinase USP7 promotes glioblastoma progression through the YBX1-NLGN3 axis.
Glucocorticoids rescue cell surface trafficking of R451C Neuroligin3 and enhance synapse formation.
Title: Glucocorticoids rescue cell surface trafficking of R451C Neuroligin3 and enhance synapse formation.
Neuron-secreted NLGN3 ameliorates ischemic brain injury via activating Galphai1/3-Akt signaling.
Title: Neuron-secreted NLGN3 ameliorates ischemic brain injury via activating Gαi1/3-Akt signaling.
Autism-linked NLGN3 is a key regulator of gonadotropin-releasing hormone deficiency.
Title: Autism-linked NLGN3 is a key regulator of gonadotropin-releasing hormone deficiency.
Expression and structural analysis of human neuroligin 2 and neuroligin 3 implicated in autism spectrum disorders.
Title: Expression and structural analysis of human neuroligin 2 and neuroligin 3 implicated in autism spectrum disorders.
Neuronal-driven glioma growth requires Galphai1 and Galphai3.
Title: Neuronal-driven glioma growth requires Gαi1 and Gαi3.
Evidence for a Contribution of the Nlgn3/Cyfip1/Fmr1 Pathway in the Pathophysiology of Autism Spectrum Disorders.
Title: Evidence for a Contribution of the Nlgn3/Cyfip1/Fmr1 Pathway in the Pathophysiology of Autism Spectrum Disorders.
We report gut symptoms in patients with the autism-associated R451C mutation encoding the neuroligin-3 protein. We show that many of the genes implicated in autism are expressed in mouse gut. The neuroligin-3 R451C mutation alters the enteric nervous system, causes gastrointestinal dysfunction, and disrupts gut microbe populations in mice.
Title: Gastrointestinal dysfunction in patients and mice expressing the autism-associated R451C mutation in neuroligin-3.
Our report of two missense variants affecting the normal localization of NLGN3 in a total of five affected individuals reinforces the involvement of the NLGN3 gene in a neurodevelopmental disorder characterized by ID and ASD.
Title: Novel mutations in NLGN3 causing autism spectrum disorder and cognitive impairment.

Submit: New GeneRIF Correction See all GeneRIFs (36)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Autism, susceptibility to, X-linked 1 MedGen: C1845540 OMIM: 300425 GeneReviews: Not available	not available

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2012-07-25) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2012-07-25) ClinGen Genome Curation Page

EBI GWAS Catalog

Description
A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of neuroligin 3 (NLGN3) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NLGN4X (e-PCR)
- UniSTS:506501

RH47725 (e-PCR)
- UniSTS:31717

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cell adhesion molecule binding	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables neurexin family protein binding	IBA Inferred from Biological aspect of Ancestor more info
enables neurexin family protein binding	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables scaffold protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables signaling receptor activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in adult behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in axon extension	ISS Inferred from Sequence or Structural Similarity more info
involved_in chemical synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
involved_in inhibitory postsynaptic potential	ISS Inferred from Sequence or Structural Similarity more info
involved_in learning	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in modulation of chemical synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
involved_in modulation of chemical synaptic transmission	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuron cell-cell adhesion	IBA Inferred from Biological aspect of Ancestor more info
involved_in neuron cell-cell adhesion	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of excitatory postsynaptic potential	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of glutamate receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of synapse assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of synaptic transmission, glutamatergic	ISS Inferred from Sequence or Structural Similarity more info
involved_in postsynaptic membrane assembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in postsynaptic membrane assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in presynapse assembly	TAS Traceable Author Statement more info	PubMed
involved_in presynaptic membrane assembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in presynaptic membrane assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in receptor-mediated endocytosis	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of respiratory gaseous exchange by nervous system process	ISS Inferred from Sequence or Structural Similarity more info
involved_in rhythmic synaptic transmission	ISS Inferred from Sequence or Structural Similarity more info
involved_in social behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in social behavior	ISS Inferred from Sequence or Structural Similarity more info
involved_in synapse assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in synapse organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in synaptic vesicle endocytosis	IBA Inferred from Biological aspect of Ancestor more info
involved_in vocalization behavior	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in asymmetric, glutamatergic, excitatory synapse	TAS Traceable Author Statement more info	PubMed
is_active_in cell surface	IBA Inferred from Biological aspect of Ancestor more info
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in endocytic vesicle	ISS Inferred from Sequence or Structural Similarity more info
located_in excitatory synapse	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	TAS Traceable Author Statement more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynaptic membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in presynapse	IEA Inferred from Electronic Annotation more info
located_in symmetric, GABA-ergic, inhibitory synapse	TAS Traceable Author Statement more info	PubMed
is_active_in synapse	IBA Inferred from Biological aspect of Ancestor more info
located_in synapse	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: neuroligin-3

Names: gliotactin homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_015874.2 RefSeqGene

Range

5002..31362

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001166660.2 → NP_001160132.1 neuroligin-3 isoform 3 precursor

See identical proteins and their annotated locations for NP_001160132.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks two alternate in-frame exons in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 3), compared to isoform 1.

Source sequence(s)

AF217411, BC028738, BC051715, BP201014

Consensus CDS

CCDS55442.1

UniProtKB/TrEMBL

X5D7L6, X5DRC3

Related

ENSP00000445298.1, ENST00000536169.6

Conserved Domains (1) summary

pfam00135
Location:36 → 584

COesterase; Carboxylesterase family
NM_001321276.2 → NP_001308205.1 neuroligin-3 isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) encodes isoform 4, which lacks a predicted signal peptide compared to isoforms 1-3.

Source sequence(s)

AF217411, AK296217, BC051715, BX641059

Consensus CDS

CCDS94627.1

UniProtKB/TrEMBL

A0A8I5KSB7, B7Z610

Related

ENSP00000508700.1, ENST00000692338.1

Conserved Domains (1) summary

pfam00135
Location:19 → 487

COesterase; Carboxylesterase family
NM_018977.4 → NP_061850.2 neuroligin-3 isoform 2 precursor

See identical proteins and their annotated locations for NP_061850.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1. Isoform 2 has also been referred to as HNL3L, or the long form.

Source sequence(s)

AF217411, BC028738, BC051715, BP201014

Consensus CDS

CCDS14407.1

UniProtKB/TrEMBL

X5D2P6, X5DRC3

Related

ENSP00000363163.3, ENST00000374051.7

Conserved Domains (1) summary

pfam00135
Location:36 → 604

COesterase; Carboxylesterase family
NM_181303.2 → NP_851820.1 neuroligin-3 isoform 1 precursor

See identical proteins and their annotated locations for NP_851820.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AF217411, AF217412, BC051715, BP201014

Consensus CDS

CCDS55441.1

UniProtKB/Swiss-Prot

B2RBK1, D2X2H6, D3DVV0, D3DVV1, Q86V51, Q8NCD0, Q9NZ94, Q9NZ95, Q9NZ96, Q9NZ97, Q9P248

UniProtKB/TrEMBL

X5DNV3, X5DRC3

Related

ENSP00000351591.4, ENST00000358741.4

Conserved Domains (1) summary

pfam00135
Location:36 → 624

COesterase; Carboxylesterase family