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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NLGN4Y
neuroligin 4 Y-linked
Chromosome Y · Yq11.221
NCBI Gene: 22829Ensembl: ENSG00000165246.15HGNC: HGNC:15529UniProt: B4DHI3
23PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
social behaviorvocalization behaviorlearningscaffold protein bindingataxia telangiectasiaprostate cancerprostate intraepithelial neoplasiacancer
✦AI Summary

NLGN4Y (neuroligin 4 Y-linked) is a cell surface adhesion protein that functions in synaptic organization and neuronal communication. Located on the Y chrY, NLGN4Y shares 97% sequence homology with its X-linked counterpart NLGN4X and encodes a postsynaptic adhesion molecule that binds to presynaptic neurexins to facilitate synapse formation and maintenance 1. The protein is involved in both excitatory and inhibitory synaptic function, contributing to synaptic assembly and neuron-to-neuron adhesion 1. NLGN4Y has emerged as a candidate gene for autism spectrum disorders (ASD), with evidence suggesting that overexpression may contribute to ASD risk in males with Y chromosome Y like 47,XYY 2. Notably, maternal immune responses against NLGN4Y protein have been associated with male homosexuality, particularly in sons with older brothers 3. In prostate cancer, reduced NLGN4Y expression correlates with higher grade tumors and increased biochemical recurrence risk, suggesting a tumor suppressor role 4. While rare missense variants like p.I679V have been identified in autism patients, the functional significance remains unclear due to limited cosegregation data 5. The gene's expression is male-specific and can be used for forensic sex determination 6.

Sources cited
1
NLGN4Y shares 97% sequence homology with NLGN4X and encodes a postsynaptic adhesion molecule that binds to neurexins
PMID: 40032531
2
NLGN4Y overexpression may contribute to ASD risk in males with Y chromosome aneuploidies
PMID: 31161682
3
Maternal immune responses against NLGN4Y are associated with male homosexuality in sons with older brothers
PMID: 29229842
4
Reduced NLGN4Y expression correlates with higher grade prostate cancer and increased recurrence risk
PMID: 27626693
5
Rare missense variant p.I679V identified in autism patient with limited functional evidence
PMID: 18628683
6
NLGN4Y expression is male-specific and can be used for forensic sex determination
PMID: 31852540
Disease Associationsⓘ20
ataxia telangiectasiaOpen Targets
0.07Suggestive
prostate cancerOpen Targets
0.03Suggestive
prostate intraepithelial neoplasiaOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
posterior cortical atrophyOpen Targets
0.02Suggestive
Adams-Oliver syndromeOpen Targets
0.01Suggestive
autismOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
glioblastoma multiformeOpen Targets
0.01Suggestive
sclerosing cholangitisOpen Targets
0.00Suggestive
lung cancerOpen Targets
0.00Suggestive
adenomaOpen Targets
0.00Suggestive
atherosclerosisOpen Targets
0.00Suggestive
breast cancerOpen Targets
0.00Suggestive
hepatocellular carcinomaOpen Targets
0.00Suggestive
Intellectual disabilityOpen Targets
0.00Suggestive
intrahepatic cholangiocarcinomaOpen Targets
0.00Suggestive
schizophreniaOpen Targets
0.00Suggestive
ulcerative colitisOpen Targets
0.00Suggestive
rosaceaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DLG3Protein interaction100%DLG4Protein interaction100%CASKProtein interaction100%DLGAP1Protein interaction100%RPS4Y1Protein interaction95%SRYProtein interaction95%
Tissue Expression6 tissues
Liver
100%
Lung
42%
Brain
4%
Ovary
2%
Bone Marrow
1%
Heart
0%
Gene Interaction Network
Click a node to explore
NLGN4YDLG3DLG4CASKDLGAP1RPS4Y1SRY
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8NFZ3
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.09LoF Tolerant
pLIⓘ
0.19Tolerant
Observed/Expected LoF0.48 [0.23–1.09]
RankingsWhere NLGN4Y stands among ~20K protein-coding genes
  • #13,470of 20,598
    Most Researched23
  • #11,095of 17,882
    Most Constrained (LOEUF)1.09
Genes detectedNLGN4Y
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Novel human sex-typing strategies based on the autism candidate gene NLGN4X and its male-specific gametologue NLGN4Y.
PMID: 31852540
Biol Sex Differ · 2019
1.00
2
Constructing Bayesian networks by integrating gene expression and copy number data identifies NLGN4Y as a novel regulator of prostate cancer progression.
PMID: 27626693
Oncotarget · 2016
0.90
3
Y chromosome gene copy number and lack of autism phenotype in a male with an isodicentric Y chromosome and absent NLGN4Y expression.
PMID: 31161682
Am J Med Genet B Neuropsychiatr Genet · 2019
0.80
4
Male homosexuality and maternal immune responsivity to the Y-linked protein NLGN4Y.
PMID: 29229842
Proc Natl Acad Sci U S A · 2018
0.70
5
Neuroligins and Neurodevelopmental Disorders: X-Linked Genetics.
PMID: 32848696
Front Synaptic Neurosci · 2020
0.60