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NLGN4X neuroligin 4 X-linked [ Homo sapiens (human) ]

Gene ID: 57502, updated on 7-Dec-2018

Summary

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Official Symbol
NLGN4Xprovided by HGNC
Official Full Name
neuroligin 4 X-linkedprovided by HGNC
Primary source
HGNC:HGNC:14287
See related
Ensembl:ENSG00000146938 MIM:300427
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
HLNX; HNL4X; NLGN4; ASPGX2; AUTSX2
Summary
This gene encodes a member of the type-B carboxylesterase/lipase protein family. The encoded protein belongs to 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. The encoded protein interacts with discs large homolog 4 (DLG4). Mutations in this gene have been associated with autism and Asperger syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
Expression
Broad expression in brain (RPKM 6.8), ovary (RPKM 4.3) and 19 other tissues See more
Orthologs
all

Genomic context

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See NLGN4X in Genome Data Viewer
Location:
Xp22.32-p22.31
Exon count:
13
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) X NC_000023.11 (5890026..6228882, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (5808067..6146916, complement)

Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta pseudogene Neighboring gene hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta pseudogene Neighboring gene uncharacterized LOC101928228 Neighboring gene uncharacterized LOC105373156 Neighboring gene microRNA 4770 Neighboring gene ribosomal protein S5 pseudogene 8

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Neuroligin 4X overexpression in human breast cancer is associated with poor relapse-free survival. Henderson HJ, et al. PLoS One, 2017. PMID 29244827, Free PMC Article
  2. The functional genetic link of NLGN4X knockdown and neurodevelopment in neural stem cells. Shi L, et al. Hum Mol Genet, 2013 Sep 15. PMID 23710042, Free PMC Article
  3. Investigating synapse formation and function using human pluripotent stem cell-derived neurons. Kim JE, et al. Proc Natl Acad Sci U S A, 2011 Feb 15. PMID 21278334, Free PMC Article
  4. Gender differences in cognitive ability associated with genetic variants of NLGN4. Zhang K, et al. Neuropsychobiology, 2010. PMID 20714171
  5. A neuroligin-4 missense mutation associated with autism impairs neuroligin-4 folding and endoplasmic reticulum export. Zhang C, et al. J Neurosci, 2009 Sep 2. PMID 19726642, Free PMC Article

See all (55) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

  1. Our data suggest that these four previously described neuroligin mutations are not primary risk factors for autism.
    Title: Not all neuroligin 3 and 4X missense variants lead to significant functional inactivation.
  2. NLGN4X might represent novel biomarkers and therapeutic targets for breast cancer. Inhibition of NLGN4X may be a new target for the prevention and treatment of breast cancer
    Title: Neuroligin 4X overexpression in human breast cancer is associated with poor relapse-free survival.
  3. Noncoding polymorphisms on NLGN4X may be associated to autism suggesting the key role of NLGN4X in autism pathophysiology and in its male prevalence.
    Title: Association Analysis of Noncoding Variants in Neuroligins 3 and 4X Genes with Autism Spectrum Disorder in an Italian Cohort.
  4. Endogenous NLGN4X is intensely phosphorylated on T707 upon PKC stimulation in human neurons.
    Title: Autism-associated mutation inhibits protein kinase C-mediated neuroligin-4X enhancement of excitatory synapses.
  5. Our data provided a further evidence for the involvement of NLGN3 and NLGN4X gene in the pathogenesis of autism in Chinese population.
    Title: Variations analysis of NLGN3 and NLGN4X gene in Chinese autism patients.
  6. The present study explores, for the first time, the contribution of NLGN3 and NLGN4X genetic variants in Greek patients with autistic disorder.
    Title: Mutation screening in the Greek population and evaluation of NLGN3 and NLGN4X genes causal factors for autism.
  7. In vitro models show NLGN4X knockdown directly impacts neurodevelopmental process during the formation of neurons and their connections.
    Title: The functional genetic link of NLGN4X knockdown and neurodevelopment in neural stem cells.
  8. Lack of association between NLGN3, NLGN4, SHANK2 and SHANK3 gene variants and autism spectrum disorder in a Chinese population.
    Title: Lack of association between NLGN3, NLGN4, SHANK2 and SHANK3 gene variants and autism spectrum disorder in a Chinese population.
  9. Neuroligins are adhesion proteins that bind to beta-neurexin to form functional synapses.
    Title: Analysis of the genes encoding neuroligins NLGN3 and NLGN4 in Bulgarian patients with autism.
  10. Five genes have been directly disrupted in Tourette Syndrome by independent genomic rearrangements and copy number variations with unique breakpoints.
    Title: Pathogenetic model for Tourette syndrome delineates overlap with related neurodevelopmental disorders including Autism.
Submit: New GeneRIF Correction See all GeneRIFs (28)

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
Asperger syndrome X-linked 2
MedGen: C1845334 OMIM: 300497 GeneReviews: Not available
Compare labs
Autism, susceptibility to, X-linked 2
MedGen: C1845539 OMIM: 300495 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
Biological insights from 108 schizophrenia-associated genetic loci.
NHGRI GWA Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from BioSystems

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  • Cell adhesion molecules (CAMs), organism-specific biosystem (from KEGG)
    Cell adhesion molecules (CAMs), organism-specific biosystemCell adhesion molecules are (glyco)proteins expressed on the cell surface and play a critical role in a wide array of biologic processes that include hemostasis, the immune response, inflammation, em...
  • Cell adhesion molecules (CAMs), conserved biosystem (from KEGG)
    Cell adhesion molecules (CAMs), conserved biosystemCell adhesion molecules are (glyco)proteins expressed on the cell surface and play a critical role in a wide array of biologic processes that include hemostasis, the immune response, inflammation, em...
  • Interactions of neurexins and neuroligins at synapses, organism-specific biosystem (from REACTOME)
    Interactions of neurexins and neuroligins at synapses, organism-specific biosystemNeurexins (NRXNs) and neuroligins (NLGNs) are best characterized synaptic cell-adhesion molecules. They are part of excitatory glutamatergic and inhibitory GABAergic synapses in mammalian brain, medi...
  • Neuronal System, organism-specific biosystem (from REACTOME)
    Neuronal System, organism-specific biosystemThe human brain contains at least 100 billion neurons, each with the ability to influence many other cells. Clearly, highly sophisticated and efficient mechanisms are needed to enable communication a...
  • Protein-protein interactions at synapses, organism-specific biosystem (from REACTOME)
    Protein-protein interactions at synapses, organism-specific biosystemSynapses constitute highly specialized sites of asymmetric cell-cell adhesion and intercellular communication. Its formation involves the recruitment of presynaptic and postsynaptic molecules at newl...

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • KIAA1260, MGC22376

Gene Ontology Provided by GOA

Function Evidence Code Pubs
cell adhesion molecule binding TAS
Traceable Author Statement
more info
 PubMed 
chloride ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
neurexin family protein binding IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
neurexin family protein binding IDA
Inferred from Direct Assay
more info
 PubMed 
neurexin family protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
protein homodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
scaffold protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
signaling receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
Process Evidence Code Pubs
adult behavior IMP
Inferred from Mutant Phenotype
more info
 PubMed 
brainstem development ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
cell-cell junction organization NAS
Non-traceable Author Statement
more info
 PubMed 
cerebellum development ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
learning IMP
Inferred from Mutant Phenotype
more info
 PubMed 
modulation of chemical synaptic transmission IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
negative regulation of excitatory postsynaptic potential IDA
Inferred from Direct Assay
more info
 PubMed 
neuron cell-cell adhesion IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
neuron cell-cell adhesion TAS
Traceable Author Statement
more info
 PubMed 
neuron differentiation NAS
Non-traceable Author Statement
more info
 PubMed 
organ growth ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
postsynaptic membrane assembly IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
presynapse assembly TAS
Traceable Author Statement
more info
 PubMed 
presynaptic membrane assembly IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
presynaptic membrane assembly IDA
Inferred from Direct Assay
more info
 PubMed 
social behavior IMP
Inferred from Mutant Phenotype
more info
 PubMed 
synapse organization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
synapse organization NAS
Non-traceable Author Statement
more info
 PubMed 
synaptic vesicle endocytosis IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
vocalization behavior IMP
Inferred from Mutant Phenotype
more info
 PubMed 
vocalization behavior ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
Component Evidence Code Pubs
asymmetric, glutamatergic, excitatory synapse TAS
Traceable Author Statement
more info
 PubMed 
cell junction IEA
Inferred from Electronic Annotation
more info
  
cell surface IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
cell surface IDA
Inferred from Direct Assay
more info
 PubMed 
dendrite IDA
Inferred from Direct Assay
more info
 PubMed 
excitatory synapse IDA
Inferred from Direct Assay
more info
 PubMed 
integral component of membrane NAS
Non-traceable Author Statement
more info
 PubMed 
integral component of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
integral component of plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
plasma membrane TAS
Traceable Author Statement
more info
  
postsynaptic density IEA
Inferred from Electronic Annotation
more info
  
postsynaptic membrane IEA
Inferred from Electronic Annotation
more info
  
presynapse IEA
Inferred from Electronic Annotation
more info
  
spanning component of membrane TAS
Traceable Author Statement
more info
 PubMed 
symmetric, GABA-ergic, inhibitory synapse TAS
Traceable Author Statement
more info
 PubMed 
synapse IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
synapse ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 

General protein information

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Preferred Names
neuroligin-4, X-linked

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

  1. NG_008881.2 RefSeqGene

    Range
    5001..343857
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001282145.1 → NP_001269074.1  neuroligin-4, X-linked

    See identical proteins and their annotated locations for NP_001269074.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) represents the longest transcript. Variants 1, 2, 3, and 4 encode the same protein.
    Source sequence(s)
    AC078989, AC079173, AK055471, CN357526
    Consensus CDS
    CCDS14126.1
    UniProtKB/Swiss-Prot
    Q8N0W4
    UniProtKB/TrEMBL
    A0A024RBV0, B3KP11
    Related
    ENSP00000370482.1, ENST00000381092.1
    Conserved Domains (1) summary
    pfam00135
    Location:46 → 590
    COesterase; Carboxylesterase family

  2. NM_001282146.1 → NP_001269075.1  neuroligin-4, X-linked

    See identical proteins and their annotated locations for NP_001269075.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR, compared to variant 3. Variants 1, 2, 3, and 4 encode the same protein.
    Source sequence(s)
    AB033086, AC078989, AK291036, DA724500
    Consensus CDS
    CCDS14126.1
    UniProtKB/Swiss-Prot
    Q8N0W4
    UniProtKB/TrEMBL
    A0A024RBV0, A8K4S1
    Related
    ENSP00000370483.3, ENST00000381093.6
    Conserved Domains (1) summary
    pfam00135
    Location:46 → 590
    COesterase; Carboxylesterase family

  3. NM_020742.3 → NP_065793.1  neuroligin-4, X-linked

    See identical proteins and their annotated locations for NP_065793.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) differs in the 5' UTR, compared to variant 3. Variants 1, 2, 3, and 4 encode the same protein.
    Source sequence(s)
    AB033086, AC078989, AC112654
    Consensus CDS
    CCDS14126.1
    UniProtKB/Swiss-Prot
    Q8N0W4
    UniProtKB/TrEMBL
    A0A024RBV0
    Related
    ENSP00000275857.6, ENST00000275857.10
    Conserved Domains (1) summary
    pfam00135
    Location:46 → 590
    COesterase; Carboxylesterase family

  4. NM_181332.3 → NP_851849.1  neuroligin-4, X-linked

    See identical proteins and their annotated locations for NP_851849.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 3. Variants 1, 2, 3, and 4 encode the same protein.
    Source sequence(s)
    AB033086, AC078989, CN357526
    Consensus CDS
    CCDS14126.1
    UniProtKB/Swiss-Prot
    Q8N0W4
    UniProtKB/TrEMBL
    A0A024RBV0
    Related
    ENSP00000370485.3, ENST00000381095.7
    Conserved Domains (1) summary
    pfam00135
    Location:46 → 590
    COesterase; Carboxylesterase family

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000023.11 Reference GRCh38.p12 Primary Assembly

    Range
    5890026..6228882 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005274564.3 → XP_005274621.1  neuroligin-4, X-linked isoform X1

    See identical proteins and their annotated locations for XP_005274621.1

    UniProtKB/Swiss-Prot
    Q8N0W4
    Conserved Domains (2) summary
    COG0657
    Location:179 → 286
    Aes; Acetyl esterase/lipase [Lipid transport and metabolism]
    pfam00135
    Location:42 → 610
    COesterase; Carboxylesterase family

  2. XM_011545548.2 → XP_011543850.1  neuroligin-4, X-linked isoform X1

    See identical proteins and their annotated locations for XP_011543850.1

    UniProtKB/Swiss-Prot
    Q8N0W4
    Conserved Domains (2) summary
    COG0657
    Location:179 → 286
    Aes; Acetyl esterase/lipase [Lipid transport and metabolism]
    pfam00135
    Location:42 → 610
    COesterase; Carboxylesterase family

  3. XM_017029691.1 → XP_016885180.1  neuroligin-4, X-linked isoform X2

    UniProtKB/Swiss-Prot
    Q8N0W4
    UniProtKB/TrEMBL
    A0A024RBV0
    Conserved Domains (1) summary
    pfam00135
    Location:46 → 590
    COesterase; Carboxylesterase family

  4. XM_011545547.2 → XP_011543849.1  neuroligin-4, X-linked isoform X1

    See identical proteins and their annotated locations for XP_011543849.1

    UniProtKB/Swiss-Prot
    Q8N0W4
    Conserved Domains (2) summary
    COG0657
    Location:179 → 286
    Aes; Acetyl esterase/lipase [Lipid transport and metabolism]
    pfam00135
    Location:42 → 610
    COesterase; Carboxylesterase family

  5. XM_005274565.2 → XP_005274622.1  neuroligin-4, X-linked isoform X1

    See identical proteins and their annotated locations for XP_005274622.1

    UniProtKB/Swiss-Prot
    Q8N0W4
    Conserved Domains (2) summary
    COG0657
    Location:179 → 286
    Aes; Acetyl esterase/lipase [Lipid transport and metabolism]
    pfam00135
    Location:42 → 610
    COesterase; Carboxylesterase family

  6. XM_017029692.1 → XP_016885181.1  neuroligin-4, X-linked isoform X2

    UniProtKB/Swiss-Prot
    Q8N0W4
    UniProtKB/TrEMBL
    A0A024RBV0
    Conserved Domains (1) summary
    pfam00135
    Location:46 → 590
    COesterase; Carboxylesterase family

  7. XM_005274566.4 → XP_005274623.1  neuroligin-4, X-linked isoform X1

    See identical proteins and their annotated locations for XP_005274623.1

    UniProtKB/Swiss-Prot
    Q8N0W4
    Conserved Domains (2) summary
    COG0657
    Location:179 → 286
    Aes; Acetyl esterase/lipase [Lipid transport and metabolism]
    pfam00135
    Location:42 → 610
    COesterase; Carboxylesterase family

  8. XM_017029693.1 → XP_016885182.1  neuroligin-4, X-linked isoform X2

    UniProtKB/Swiss-Prot
    Q8N0W4
    UniProtKB/TrEMBL
    A0A024RBV0
    Conserved Domains (1) summary
    pfam00135
    Location:46 → 590
    COesterase; Carboxylesterase family

  9. XM_006724504.3 → XP_006724567.1  neuroligin-4, X-linked isoform X1

    See identical proteins and their annotated locations for XP_006724567.1

    UniProtKB/Swiss-Prot
    Q8N0W4
    Related
    ENSP00000439203.3, ENST00000538097.6
    Conserved Domains (2) summary
    COG0657
    Location:179 → 286
    Aes; Acetyl esterase/lipase [Lipid transport and metabolism]
    pfam00135
    Location:42 → 610
    COesterase; Carboxylesterase family
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8N0W4.1 GenPept UniProtKB/Swiss-Prot:Q8N0W4

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