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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
NLGN4X
neuroligin 4 X-linked
Chromosome X Β· Xp22.32-p22.31
NCBI Gene: 57502Ensembl: ENSG00000146938.17HGNC: HGNC:14287UniProt: A8K4S1
75PubMed Papers
21Diseases
0Drugs
12Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingchloride ion bindingneurexin family protein bindingprotein homodimerization activityautismneurodegenerative diseasegenetic disorderX-linked intellectual disability
✦AI Summary

NLGN4X encodes neuroligin-4 X-linked, a postsynaptic cell adhesion molecule that plays a critical role in synapse formation and function through interactions with presynaptic neurexin family members 12. The protein regulates synaptic homeostasis and the balance between excitation and inhibition at synapses 1. NLGN4X function is modulated by phosphorylation at serine 712, which controls spine density and synaptic transmission, with phosphorylation by PKA reducing mature mushroom spines while unphosphorylated forms increase spine density and miniature excitatory postsynaptic current frequency 3. NLGN4X is strongly associated with autism spectrum disorders and intellectual disability, with multiple missense mutations identified in Chinese autism patients that are predicted to be damaging and absent in controls 1. A promoter mutation causing increased NLGN4X expression has been linked to autism and profound mental retardation 4. The gene forms an X-Y pair with NLGN4Y, sharing 97% homology, though NLGN4Y shows severe functional deficits and cannot compensate for ASD-associated NLGN4X mutations 5. NLGN4X also serves as a tumor-associated antigen overexpressed in gliomas, making it a potential target for immunotherapy 6.

Sources cited
1
NLGN4X is a postsynaptic cell adhesion molecule that interacts with neurexins and regulates synaptic homeostasis, with mutations associated with autism
PMID: 24570023
2
NLGN4X is an X-linked synaptic protein strongly linked to autism spectrum disorders and intellectual disability
PMID: 32848696
3
NLGN4X phosphorylation at serine 712 by PKA regulates spine density and synaptic transmission
PMID: 40032531
4
A promoter mutation causing increased NLGN4X expression is associated with autism and mental retardation
PMID: 19545860
5
NLGN4X forms an X-Y pair with NLGN4Y sharing 97% homology, but NLGN4Y has severe functional deficits
PMID: 32243781
6
NLGN4X is overexpressed in gliomas and serves as a tumor-associated antigen for immunotherapy
PMID: 37715782
Disease Associationsβ“˜21
autismOpen Targets
0.63Moderate
neurodegenerative diseaseOpen Targets
0.49Moderate
genetic disorderOpen Targets
0.47Moderate
X-linked intellectual disabilityOpen Targets
0.42Moderate
X-linked complex neurodevelopmental disorderOpen Targets
0.40Weak
insomniaOpen Targets
0.38Weak
schizophreniaOpen Targets
0.38Weak
Asperger syndromeOpen Targets
0.16Weak
Intellectual disabilityOpen Targets
0.15Weak
autism spectrum disorderOpen Targets
0.12Weak
melanomaOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.07Suggestive
Alzheimer diseaseOpen Targets
0.03Suggestive
breast carcinomaOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.02Suggestive
ovarian carcinomaOpen Targets
0.02Suggestive
Adams-Oliver syndromeOpen Targets
0.02Suggestive
Neurodevelopmental disorderOpen Targets
0.01Suggestive
alcohol dependenceOpen Targets
0.01Suggestive
triple-negative breast cancerOpen Targets
0.01Suggestive
Autism, X-linked 2UniProt
Pathogenic Variants12
NM_181332.3(NLGN4X):c.259C>T (p.Arg87Trp)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 87
NM_181332.3(NLGN4X):c.1075C>T (p.Gln359Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2026β†’ Residue 359
NM_181332.3(NLGN4X):c.779_782dup (p.Leu262fs)Pathogenic
Autism, susceptibility to, X-linked 2
β˜…β˜†β˜†β˜†2025β†’ Residue 262
NM_181332.3(NLGN4X):c.1747C>T (p.Arg583Trp)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2024β†’ Residue 583
NM_181332.3(NLGN4X):c.626-1G>ALikely pathogenic
Autism, susceptibility to, X-linked 2
β˜…β˜†β˜†β˜†2023
NM_181332.3(NLGN4X):c.301C>T (p.Arg101Ter)Pathogenic
Autism, susceptibility to, X-linked 2|not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 101
NM_181332.3(NLGN4X):c.625+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2022
NC_000023.11:g.(?_5892817)_(6383998_?)delPathogenic
not provided
β˜…β˜†β˜†β˜†2018
NM_181332.3(NLGN4X):c.334dup (p.Gln112fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2017β†’ Residue 112
GRCh38/hg38 Xp22.32-22.31(chrX:5982467-6100650)x0Pathogenic
See cases
β˜†β˜†β˜†β˜†2013
GRCh38/hg38 Xp22.32(chrX:5885166-5914976)x0Pathogenic
See cases
β˜†β˜†β˜†β˜†2011
NM_181332.3(NLGN4X):c.1254_1255del (p.Glu418fs)Pathogenic
Autism, susceptibility to, X-linked 2|X-linked intellectual disability
β˜†β˜†β˜†β˜†2004β†’ Residue 418
View on ClinVar β†—
Related Genes
DLG2Protein interaction100%DLG3Protein interaction100%DLG4Protein interaction100%CASKProtein interaction100%DLGAP2Protein interaction100%DLGAP1Protein interaction100%
Tissue Expression6 tissues
Ovary
100%
Brain
98%
Heart
37%
Liver
7%
Lung
2%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
NLGN4XDLG2DLG3DLG4CASKDLGAP2DLGAP1
PROTEIN STRUCTURE
Preparing viewer…
PDB3BE8 Β· 2.20 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.19Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.07 [0.03–0.19]
RankingsWhere NLGN4X stands among ~20K protein-coding genes
  • #6,349of 20,598
    Most Researched75
  • #2,678of 5,498
    Most Pathogenic Variants12
  • #408of 17,882
    Most Constrained (LOEUF)0.19 Β· top 5%
Genes detectedNLGN4X
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Analysis of the human kidney transcriptome and plasma proteome identifies markers of proximal tubule maladaptation to injury.
PMID: 38091407
Sci Transl Med Β· 2023
1.00
2
Variations analysis of NLGN3 and NLGN4X gene in Chinese autism patients.
PMID: 24570023
Mol Biol Rep Β· 2014
0.90
3
Novel human sex-typing strategies based on the autism candidate gene NLGN4X and its male-specific gametologue NLGN4Y.
PMID: 31852540
Biol Sex Differ Β· 2019
0.80
4
NLGN4X TCR transgenic T cells to treat gliomas.
PMID: 37715782
Neuro Oncol Β· 2024
0.70
5
Phosphorylation of NLGN4X Regulates Spinogenesis and Synaptic Function.
PMID: 40032531
eNeuro Β· 2025
0.60