LRRTM2

Chr 5

leucine rich repeat transmembrane neuronal 2

NCBI Gene: 26045ENSG00000146006UniProt: O43300

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]

0
ClinVar variants
0
Pathogenic / LP
0.81
pLI score
0
Active trials
Clinical Summary— LRRTM2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.81) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.42LOEUF
pLI 0.809
Z-score 3.36
OE 0.16 (0.07–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.89Z-score
OE missense 0.68 (0.60–0.77)
190 obs / 278.7 exp
Tolerant

Mild missense constraint

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.0.16 (0.07–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.60–0.77)
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.0.89
0≤1.21.6
LoF obs/exp: 3 / 18.6Missense obs/exp: 190 / 278.7Syn Z: 0.94

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

LRRTM2 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Structural insights into modulation and selectivity of transsynaptic neurexin-LRRTM interaction.
Yamagata A et al.·Nat Commun
2018
Neurexin 1 variants as risk factors for suicide death.
William N et al.·Mol Psychiatry
2021
A Systematic Structure-Function Characterization of a Human Mutation in Neurexin-3α Reveals an Extracellular Modulatory Sequence That Stabilizes Neuroligin-1 Binding to Enhance the Postsynaptic Properties of Excitatory Synapses.
Stokes EG et al.·J Neurosci
2024
Truncating mutations in NRXN2 and NRXN1 in autism spectrum disorders and schizophrenia.
Gauthier J et al.·Hum Genet
2011
Modeling a Neurexin-3α Human Mutation in Mouse Neurons Identifies a Novel Role in the Regulation of Transsynaptic Signaling and Neurotransmitter Release at Excitatory Synapses.
Restrepo S et al.·J Neurosci
2019Functional
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

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools