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

Summary

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

Location:: Xp22.32-p22.31

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (5890042..6228867, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (5442298..5781161, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (5808083..6146908, complement)

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?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Submit: New GeneRIF Correction See all GeneRIFs (37)

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	Compare labs

EBI GWAS Catalog

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

DXS7979 (e-PCR)
- UniSTS:154376

DXS996 (e-PCR), detects polymorphism
- UniSTS:88080

SHGC-155196 (e-PCR)
- UniSTS:185108

G43607 (e-PCR)
- UniSTS:95042

DXS1118E (e-PCR)
- UniSTS:99399

SHGC-147783 (e-PCR)
- UniSTS:172876

G66233 (e-PCR)
- UniSTS:230221

G66396 (e-PCR)
- UniSTS:230234

DXS7042 (e-PCR)
- UniSTS:42604

DXYS125 (e-PCR)
- UniSTS:31387

DXS7031E (e-PCR)
- UniSTS:49072

DXS996 (e-PCR), detects polymorphism
- UniSTS:2253

SHGC-150657 (e-PCR)
- UniSTS:173262

RH15923 (e-PCR)
- UniSTS:86485

DXS7538 (e-PCR)
- UniSTS:153835

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	IBA Inferred from Biological aspect of Ancestor more info
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
enables signaling receptor activity	IBA Inferred from Biological aspect of Ancestor more info

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 chemical synaptic transmission	IBA Inferred from Biological aspect of Ancestor 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	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	IBA Inferred from Biological aspect of Ancestor more info
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 postsynaptic membrane assembly	IBA Inferred from Biological aspect of Ancestor 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	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 synaptic vesicle endocytosis	IBA Inferred from Biological aspect of Ancestor more info
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
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 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
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
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
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	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

NG_008881.2 RefSeqGene

Range

5016..343841

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001282145.2 → 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

Q6UX10, Q8N0W4, Q9ULG0

UniProtKB/TrEMBL

A8K4S1, B3KP11

Related

ENSP00000370482.1, ENST00000381092.1

Conserved Domains (1) summary

pfam00135
Location:46 → 590

COesterase; Carboxylesterase family
NM_001282146.2 → 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

Q6UX10, Q8N0W4, Q9ULG0

UniProtKB/TrEMBL

A8K4S1, B3KP11

Related

ENSP00000370483.3, ENST00000381093.6

Conserved Domains (1) summary

pfam00135
Location:46 → 590

COesterase; Carboxylesterase family
NM_020742.4 → 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

Q6UX10, Q8N0W4, Q9ULG0

UniProtKB/TrEMBL

A8K4S1, B3KP11

Related

ENSP00000275857.6, ENST00000275857.10

Conserved Domains (1) summary

pfam00135
Location:46 → 590

COesterase; Carboxylesterase family
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

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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000023.11 Reference GRCh38.p14 Primary Assembly

Range

5890042..6228867 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
XM_047442281.1 → XP_047298237.1 neuroligin-4, X-linked isoform X2

UniProtKB/Swiss-Prot

Q6UX10, Q8N0W4, Q9ULG0
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
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
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
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
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
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
XM_047442282.1 → XP_047298238.1 neuroligin-4, X-linked isoform X2

UniProtKB/Swiss-Prot

Q6UX10, Q8N0W4, Q9ULG0
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