LRRTM2
protein-codingleucine rich repeat transmembrane neuronal 2
Gene summary
Predicted to enable neurexin family protein binding activity. Predicted to be involved in regulation of postsynaptic density assembly. Predicted to act upstream of or within several processes, including long-term synaptic potentiation; negative regulation of receptor internalization; and positive regulation of synapse assembly. Is active in GABA-ergic synapse and postsynaptic specialization membrane. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.4 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 LRRTM2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015564.3. 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 | 1 | ||||
| missense | 41 | 1 | 42 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 41 | 2 | 0 | 43 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056379.1 | 2 | MANE Select | |
| Ensembl | ENSP00000274711.5 | 2 | MANE Select | |
| Ensembl | ENSP00000428398.1 | 2 | Standard | |
| Ensembl | ENSP00000428398.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neuronal System
- Neurexins and neuroligins
- Protein-protein interactions at synapses
Biological Process
- negative regulation of receptor internalization
- synapse organization
- positive regulation of synapse assembly
- long-term synaptic potentiation
- regulation of postsynaptic density assembly
Molecular Function
- neurexin family protein binding
Cellular Component
- cell junction
- excitatory synapse
- Schaffer collateral - CA1 synapse
- hippocampal mossy fiber to CA3 synapse
- glutamatergic synapse
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000274711
- Coding exons
- 2
- Length
- 6446
- Individuals with no LoFs
- 124633
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 124637
- p
- 0.0000160
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.89 | 190 | 279 | 0.682 | 0.0000152 | 3387 |
| Missense (PolyPhen) | 55 | 112.31 | 0.48969 | 1428 | ||
| Synonymous | 0.942 | 97 | 110 | 0.886 | 0.00000598 | 1022 |
| Loss of Function | 3.36 | 3 | 18.6 | 0.161 | 0.00000115 | 213 |
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 | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000027 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the development and maintenance of excitatory synapse in the vertebrate nervous system. Regulates surface expression of AMPA receptors and instructs the development of functional glutamate release sites. Acts as a ligand for the presynaptic receptors NRXN1-A and NRXN1-B (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- LoFtool
- 0.246
- RVIS EVS
- -0.6
- RVIS percentile EVS
- 17.75
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.394
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |