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

    Gene ID: 57502, updated on 14-Nov-2024

    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; AllianceGenome:HGNC:14287
    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
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    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
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (5890042..6228867, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (5442298..5781161, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (5808083..6146908, complement)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene small nucleolar RNA SNORA20 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:5398809-5399309 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29379 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29380 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:5566951-5567836 Neighboring gene long intergenic non-protein coding RNA 3070 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:5945089-5945662 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:6119195-6119695 Neighboring gene uncharacterized LOC105373156 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:6194636-6195374 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:6197302-6198185 Neighboring gene microRNA 4770 Neighboring gene RPS5 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 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. The distribution of neuroligin4, an autism-related postsynaptic molecule, in the human brain. Toya A, et al. Mol Brain, 2023 Feb 6. PMID 36747195, Free PMC Article
    2. 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
    3. 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
    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 (70) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Late stage melanoma is hallmarked by low NLGN4X expression leading to HIF1A accumulation.
      Title: Late stage melanoma is hallmarked by low NLGN4X expression leading to HIF1A accumulation.
    2. The distribution of neuroligin4, an autism-related postsynaptic molecule, in the human brain.
      Title: The distribution of neuroligin4, an autism-related postsynaptic molecule, in the human brain.
    3. RNA sequencing and functional studies of patient-derived cells reveal that neurexin-1 and regulators of this pathway are associated with poor outcomes in Ewing sarcoma.
      Title: RNA sequencing and functional studies of patient-derived cells reveal that neurexin-1 and regulators of this pathway are associated with poor outcomes in Ewing sarcoma.
    4. Autism-associated variants of neuroligin 4X impair synaptogenic activity by various molecular mechanisms.
      Title: Autism-associated variants of neuroligin 4X impair synaptogenic activity by various molecular mechanisms.
    5. Pathogenic paternally inherited NLGN4X deletion in a female with autism spectrum disorder: Clinical, cytogenetic, and molecular characterization.
      Title: Pathogenic paternally inherited NLGN4X deletion in a female with autism spectrum disorder: Clinical, cytogenetic, and molecular characterization.
    6. An Autism-Associated Mutation Impairs Neuroligin-4 Glycosylation and Enhances Excitatory Synaptic Transmission in Human Neurons.
      Title: An Autism-Associated Mutation Impairs Neuroligin-4 Glycosylation and Enhances Excitatory Synaptic Transmission in Human Neurons.
    7. A Cluster of Autism-Associated Variants on X-Linked NLGN4X Functionally Resemble NLGN4Y.
      Title: A Cluster of Autism-Associated Variants on X-Linked NLGN4X Functionally Resemble NLGN4Y.
    8. Neuroligin-4 is primarily expressed in cerebral cortex and localized to excitatory synapses. Overexpression of NLGN4 in human embryonic stem cell-derived neurons resulted in an increase in excitatory synapse numbers but a remarkable decrease in synaptic strength. The syndromic autism mutation NLGN4-R704C elicited more excitatory synapses but with increased functional synaptic transmission via a postsynaptic mechanism.
      Title: Neuroligin-4 Regulates Excitatory Synaptic Transmission in Human Neurons.
    9. the effects of rs1421589 within NRXN1, rs4844285 and rs11795613 within NLGN3, as well as rs5961397 within NLGX4X on Hirschsprung's disease phenotypes were also statistically significant.
      Title: Significance of neurexin and neuroligin polymorphisms in regulating risk of Hirschsprung's disease.
    10. Steady-state fluorescence and microscale thermophoresis experiments allowed the authors to confirm the binding of some of mycotoxins to acetylcholinesterase and X-linked neuroligin 4, two proteins involved in synapse activity and, particularly for the second protein, neuronal plasticity and development.
      Title: Binding of mycotoxins to proteins involved in neuronal plasticity: a combined in silico/wet investigation.
    Submit: New GeneRIF Correction See all GeneRIFs (38)

    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 2
    MedGen: C1845539 OMIM: 300495 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Biological insights from 108 schizophrenia-associated genetic loci.
    EBI GWAS 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)

    Pathways from PubChem

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

    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
      5016..343841
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001282145.2 → NP_001269074.1  neuroligin-4, X-linked precursor

      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
      Q6UX10, Q8N0W4, Q9ULG0
      UniProtKB/TrEMBL
      A8K4S1, B3KP11
      Related
      ENSP00000370482.1, ENST00000381092.1
      Conserved Domains (1) summary
      pfam00135
      Location:46 → 590
      COesterase; Carboxylesterase family

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

      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
      Q6UX10, Q8N0W4, Q9ULG0
      UniProtKB/TrEMBL
      A8K4S1, B3KP11
      Related
      ENSP00000370483.3, ENST00000381093.6
      Conserved Domains (1) summary
      pfam00135
      Location:46 → 590
      COesterase; Carboxylesterase family

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

      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
      Q6UX10, Q8N0W4, Q9ULG0
      UniProtKB/TrEMBL
      A8K4S1, B3KP11
      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 precursor

      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
      Q6UX10, Q8N0W4, Q9ULG0
      UniProtKB/TrEMBL
      A8K4S1, B3KP11
      Related
      ENSP00000370485.3, ENST00000381095.8
      Conserved Domains (1) summary
      pfam00135
      Location:46 → 590
      COesterase; Carboxylesterase family

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      5890042..6228867 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

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

      See identical proteins and their annotated locations for XP_005274621.1

      UniProtKB/TrEMBL
      A8K4S1, B3KP11
      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_011545548.3 → XP_011543850.1  neuroligin-4, X-linked isoform X1

      See identical proteins and their annotated locations for XP_011543850.1

      UniProtKB/TrEMBL
      A8K4S1, B3KP11
      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_047442281.1 → XP_047298237.1  neuroligin-4, X-linked isoform X2

      UniProtKB/Swiss-Prot
      Q6UX10, Q8N0W4, Q9ULG0

    4. XM_005274565.3 → XP_005274622.1  neuroligin-4, X-linked isoform X1

      See identical proteins and their annotated locations for XP_005274622.1

      UniProtKB/TrEMBL
      A8K4S1, B3KP11
      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_017029691.2 → XP_016885180.1  neuroligin-4, X-linked isoform X2

      UniProtKB/Swiss-Prot
      Q6UX10, Q8N0W4, Q9ULG0
      UniProtKB/TrEMBL
      A8K4S1, B3KP11
      Conserved Domains (1) summary
      pfam00135
      Location:46 → 590
      COesterase; Carboxylesterase family

    6. XM_011545547.3 → XP_011543849.1  neuroligin-4, X-linked isoform X1

      See identical proteins and their annotated locations for XP_011543849.1

      UniProtKB/TrEMBL
      A8K4S1, B3KP11
      Conserved Domains (2) summary
      COG0657
      Location:179 → 286
      Aes; Acetyl esterase/lipase [Lipid transport and metabolism]
      pfam00135
      Location:42 → 610
      COesterase; Carboxylesterase family

    7. XM_017029692.2 → XP_016885181.1  neuroligin-4, X-linked isoform X2

      UniProtKB/Swiss-Prot
      Q6UX10, Q8N0W4, Q9ULG0
      UniProtKB/TrEMBL
      A8K4S1, B3KP11
      Conserved Domains (1) summary
      pfam00135
      Location:46 → 590
      COesterase; Carboxylesterase family

    8. XM_005274566.5 → XP_005274623.1  neuroligin-4, X-linked isoform X1

      See identical proteins and their annotated locations for XP_005274623.1

      UniProtKB/TrEMBL
      A8K4S1, B3KP11
      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

    9. XM_017029693.2 → XP_016885182.1  neuroligin-4, X-linked isoform X2

      UniProtKB/Swiss-Prot
      Q6UX10, Q8N0W4, Q9ULG0
      UniProtKB/TrEMBL
      A8K4S1, B3KP11
      Conserved Domains (1) summary
      pfam00135
      Location:46 → 590
      COesterase; Carboxylesterase family

    10. XM_047442282.1 → XP_047298238.1  neuroligin-4, X-linked isoform X2

      UniProtKB/Swiss-Prot
      Q6UX10, Q8N0W4, Q9ULG0

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

      See identical proteins and their annotated locations for XP_006724567.1

      UniProtKB/TrEMBL
      A8K4S1, B3KP11
      Conserved Domains (2) summary
      COG0657
      Location:179 → 286
      Aes; Acetyl esterase/lipase [Lipid transport and metabolism]
      pfam00135
      Location:42 → 610
      COesterase; Carboxylesterase family

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      5442298..5781161 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054327444.1 → XP_054183419.1  neuroligin-4, X-linked isoform X1

    2. XM_054327449.1 → XP_054183424.1  neuroligin-4, X-linked isoform X1

    3. XM_054327453.1 → XP_054183428.1  neuroligin-4, X-linked isoform X2

      UniProtKB/Swiss-Prot
      Q6UX10, Q8N0W4, Q9ULG0

    4. XM_054327451.1 → XP_054183426.1  neuroligin-4, X-linked isoform X2

      UniProtKB/Swiss-Prot
      Q6UX10, Q8N0W4, Q9ULG0

    5. XM_054327450.1 → XP_054183425.1  neuroligin-4, X-linked isoform X2

      UniProtKB/Swiss-Prot
      Q6UX10, Q8N0W4, Q9ULG0

    6. XM_054327446.1 → XP_054183421.1  neuroligin-4, X-linked isoform X1

    7. XM_054327445.1 → XP_054183420.1  neuroligin-4, X-linked isoform X1

    8. XM_054327448.1 → XP_054183423.1  neuroligin-4, X-linked isoform X1

    9. XM_054327452.1 → XP_054183427.1  neuroligin-4, X-linked isoform X2

      UniProtKB/Swiss-Prot
      Q6UX10, Q8N0W4, Q9ULG0

    10. XM_054327454.1 → XP_054183429.1  neuroligin-4, X-linked isoform X2

      UniProtKB/Swiss-Prot
      Q6UX10, Q8N0W4, Q9ULG0

    11. XM_054327447.1 → XP_054183422.1  neuroligin-4, X-linked isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8N0W4.1 GenPept UniProtKB/Swiss-Prot:Q8N0W4

    Gene LinkOut

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