NLGN2
protein-codingneuroligin 2, the group of Neuroligins
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NLGN2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020795.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 66 | 6 | 73 | ||
| missense | 1 | 154 | 4 | 159 | ||
| nonsense | 5 | 5 | ||||
| start loss | 0 | |||||
| frameshift | 4 | 4 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 1 | 166 | 70 | 6 | 243 |
Highest pathogenic variant AF is 6.8406285e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065846.1 | 7 | MANE Select | |
| Ensembl | ENSP00000305288.2 | 7 | MANE Select | |
| Ensembl | ENSP00000461092.1 | 4 | Standard | |
| Ensembl | ENSP00000461168.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell adhesion molecules (CAMs) - Homo sapiens (human)
- Neuronal System
- Neurexins and neuroligins
- Protein-protein interactions at synapses
Biological Process
- regulation of respiratory gaseous exchange by neurological system process
- neuron cell-cell adhesion
- synapse assembly
- sensory perception of pain
- positive regulation of insulin secretion
Molecular Function
- signaling receptor activity
- neurexin family protein binding
- identical protein binding
- cell adhesion molecule binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- cell surface
- membrane
- cell junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000302926
- Coding exons
- 7
- Length
- 14987
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 4.47 | 225 | 508 | 0.442 | 0.0000367 | 5271 |
| Missense (PolyPhen) | 83 | 300.88 | 0.27585 | 3091 | ||
| Synonymous | 0.278 | 234 | 239 | 0.977 | 0.0000194 | 1807 |
| Loss of Function | 4.50 | 0 | 23.6 | 0.00 | 0.00000102 | 277 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transmembrane scaffolding protein involved in cell-cell interactions via its interactions with neurexin family members. Mediates cell-cell interactions both in neurons and in other types of cells, such as Langerhans beta cells. Plays a role in synapse function and synaptic signal transmission, especially via gamma- aminobutyric acid receptors (GABA(A) receptors). Functions by recruiting and clustering synaptic proteins. Promotes clustering of postsynaptic GABRG2 and GPHN. Modulates signaling by inhibitory synapses, and thereby plays a role in controlling the ratio of signaling by excitatory and inhibitory synapses and information processing. Required for normal signal amplitude from inhibitory synapses, but is not essential for normal signal frequency. May promote the initial formation of synapses, but is not essential for this. In vitro, triggers the de novo formation of presynaptic structures. Mediates cell-cell interactions between Langerhans beta cells and modulates insulin secretion (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.113
Intolerance Scores
- RVIS EVS
- -1.02
- RVIS percentile EVS
- 7.94
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.767
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |