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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NRXN2
neurexin 2
Chromosome 11 · 11q13.1
NCBI Gene: 9379Ensembl: ENSG00000110076.21HGNC: HGNC:8009UniProt: A0A8I5KY42
41PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
vocalization behavioradult behaviorsocial behaviorvocal learninggoutautism spectrum disorderautismMyocardial Ischemia
✦AI Summary

NRXN2 is a presynaptic cell adhesion molecule that functions as a synaptic organizer critical for neurodevelopment and neuropsychiatric health 1. As part of the neurexin family (NRXN1, NRXN2, NRXN3), NRXN2 interacts with postsynaptic neuroligins to regulate synaptic assembly and function 2. At the molecular level, NRXN2 acts as a context-dependent specifier of synapse properties and maintains the balance between excitatory and inhibitory neurotransmission (E/I balance), a process essential for normal neural development 3. Genetic variants in NRXN2 are associated with multiple neurodevelopmental and neuropsychiatric disorders. Homozygous NRXN2 mutations cause severe phenotypes including global developmental delay, severe intellectual disability, epilepsy, and speech delay 4. Heterozygous NRXN2 variants contribute to autism spectrum disorder (ASD) and early infantile epileptic encephalopathy (EIEE) 3, with digenic NRXN1/NRXN2 variants associated with respiratory dysfunction and seizures 5. Clinically, NRXN2 dysfunction disrupts proper alternative splicing patterns during brain development 6 and reduces astrocyte-neuron interactions during aging 7. These findings establish NRXN2 as a critical determinant of normal synaptic function and brain development, with mutations causing severe neurological consequences.

Sources cited
1
Neurexins are presynaptic synaptic organizers; NRXN2 variants implicated in ASD, schizophrenia, and intellectual disability
PMID: 29221905
2
NRXN2 variants associated with neurodevelopmental disorders; NRXN-NLGN interaction critical for synaptic function
PMID: 38739110
3
NRXN2 functions as context-dependent specifier of synapse properties; maintains E/I balance; implicated in ASD
PMID: 36923655
4
Homozygous NRXN2 missense variant causes global developmental delay, severe intellectual disability, epilepsy, and speech delay
PMID: 39748282
5
Digenic NRXN1/NRXN2 variants associated with EIEE, respiratory dysfunction, and seizures
PMID: 30709877
6
NRXN2 expression affected by spliceosomal dysfunction; altered alternative splicing in neurodevelopmental disorders
PMID: 40608414
7
Age-related reduction in molecular interactions between astrocytes and neurons involving NRXN2
PMID: 41006292
Disease Associationsⓘ20
goutOpen Targets
0.44Moderate
autism spectrum disorderOpen Targets
0.38Weak
autismOpen Targets
0.38Weak
Myocardial IschemiaOpen Targets
0.17Weak
mathematical abilityOpen Targets
0.17Weak
ArthropathyOpen Targets
0.16Weak
edemaOpen Targets
0.15Weak
Intellectual disabilityOpen Targets
0.15Weak
brain compressionOpen Targets
0.15Weak
osteoarthritis, kneeOpen Targets
0.14Weak
epilepsyOpen Targets
0.12Weak
sleep apneaOpen Targets
0.11Weak
developmental and epileptic encephalopathy, 1Open Targets
0.11Weak
genetic developmental and epileptic encephalopathyOpen Targets
0.11Weak
infantile epileptic-dyskinetic encephalopathyOpen Targets
0.11Weak
infantile spasmsOpen Targets
0.11Weak
Severe intellectual disabilityOpen Targets
0.11Weak
Spasticity - intellectual disability - X-linked epilepsyOpen Targets
0.11Weak
obesityOpen Targets
0.10Weak
overnutritionOpen Targets
0.09Suggestive
Pathogenic Variants1
NM_015080.4(NRXN2):c.433C>T (p.Gln145Ter)Likely pathogenic
NRXN2-related developmental disorder
★☆☆☆2025→ Residue 145
View on ClinVar ↗
Related Genes
POMGNT1Protein interaction99%CBLN1Protein interaction99%GRID2Protein interaction99%LRRTM3Protein interaction91%LRRTM1Protein interaction90%NRXN1Protein interaction87%
Tissue Expression6 tissues
Brain
100%
Ovary
41%
Bone Marrow
12%
Liver
9%
Heart
3%
Lung
1%
Gene Interaction Network
Click a node to explore
NRXN2POMGNT1CBLN1GRID2LRRTM3LRRTM1NRXN1
PROTEIN STRUCTURE
Preparing viewer…
PDB4NXR · 1.90 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.32Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.23 [0.17–0.32]
RankingsWhere NRXN2 stands among ~20K protein-coding genes
  • #10,045of 20,598
    Most Researched41
  • #5,159of 5,498
    Most Pathogenic Variants1
  • #1,268of 17,882
    Most Constrained (LOEUF)0.32 · top 10%
Genes detectedNRXN2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Mutations in the spliceosomal gene SNW1 cause neurodevelopment disorders with microcephaly.
PMID: 40608414
J Clin Invest · 2025
1.00
2
Unravelling the molecular landscape of endometrial cancer subtypes: insights from multiomics analysis.
PMID: 38775562
Int J Surg · 2024
0.90
3
Neurexins and neuropsychiatric disorders.
PMID: 29221905
Neurosci Res · 2018
0.80
4
Aging in mice alters regionally enriched striatal astrocytes.
PMID: 41006292
Nat Commun · 2025
0.70
5
Advances in neurexin studies and the emerging role of neurexin-2 in autism spectrum disorder.
PMID: 36923655
Front Mol Neurosci · 2023
0.60