NLGN2

Chr 17

neuroligin 2

NCBI Gene: 57555ENSG00000169992UniProt: Q8NFZ4

This gene encodes a member of 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. [provided by RefSeq, Jul 2008]

287
ClinVar variants
28
Pathogenic / LP
1.00
pLI score· haploinsufficient
2
Active trials
Clinical Summary— NLGN2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
28 Pathogenic / Likely Pathogenic· 167 VUS of 287 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.13LOEUF
pLI 1.000
Z-score 4.50
OE 0.00 (0.00–0.13)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
4.47Z-score
OE missense 0.44 (0.40–0.49)
225 obs / 508.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.44 (0.40–0.49)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 0 / 23.6Missense obs/exp: 225 / 508.5Syn Z: 0.28

ClinVar Variant Classifications

287 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic4
VUS167
Likely Benign72
Benign19
Conflicting1
24
Pathogenic
4
Likely Pathogenic
167
VUS
72
Likely Benign
19
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
1
3
0
4
VUS
5
143
18
1
167
Likely Benign
0
2
9
61
72
Benign
0
2
4
13
19
Conflicting
—1
Total51485875287

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NLGN2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
NEUROLIGIN 2; NLGN2
MIM #606479 · *
📖
GeneReview available — NLGN2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
NLGN1 and NLGN2 in the prefrontal cortex: their role in memory consolidation and strengthening.
Katzman A et al.·Curr Opin Neurobiol
2018Review
Large-scale discovery of novel neurodevelopmental disorder-related genes through a unified analysis of single-nucleotide and copy number variants.
Hamanaka K et al.·Genome Med
2022
Chromosomal microarray analysis of consecutive individuals with autism spectrum disorders or learning disability presenting for genetic services.
Roberts JL et al.·Gene
2014
Expression alteration of Neuroligin family gene in attention deficit and hyperactivity disorder and autism spectrum disorder.
Bay H et al.·Res Dev Disabil
2023
Identification and functional characterization of rare mutations of the neuroligin-2 gene (NLGN2) associated with schizophrenia.
Sun C et al.·Hum Mol Genet
2011Functional
Neuroligin 2 nonsense variant associated with anxiety, autism, intellectual disability, hyperphagia, and obesity.
Parente DJ et al.·Am J Med Genet A
2017Case report
Quantification of the trans-synaptic partners neurexin-neuroligin in CSF of neurodegenerative diseases by parallel reaction monitoring mass spectrometry.
Camporesi E et al.·EBioMedicine
2022
Temporal Effects of Disease Signature Genes and Core Mechanisms in the Hyperacute Phase of Acute Ischemic Stroke: A Bioinformatics Analysis and Experimental Validation.
Ding PL et al.·Mediators Inflamm
2025Functional
Truncating mutations in NRXN2 and NRXN1 in autism spectrum disorders and schizophrenia.
Gauthier J et al.·Hum Genet
2011
De novo duplication of 17p13.1-p13.2 in a patient with intellectual disability and obesity.
Kuroda Y et al.·Am J Med Genet A
2014Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Morbid ObesityBariatric SurgeryTelerehabilitation

Exercise to Fight Obesity

RECRUITING
NCT06934681Phase NAInstituto de Investigacion Sanitaria La FeStarted 2025-05-19
Usual Care GroupControlled exercise with telerehabilitation
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools