NRXN3

Chr 14

neurexin 3

Also known as: C14orf60

NRXN3 encodes a presynaptic neuronal cell adhesion molecule that functions in trans-synaptic complexes to regulate NMDA and AMPA receptor activity at hippocampal synapses. Mutations cause neurodevelopmental disorders including autism spectrum disorder and intellectual disability with autosomal dominant inheritance. The gene is highly constrained against loss-of-function mutations, indicating that NRXN3 variants are likely to have significant clinical impact.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.11
Clinical SummaryNRXN3
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.11LOEUF
pLI 1.000
Z-score 5.90
OE 0.02 (0.010.11)
Highly constrained

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

Missense Constraint
3.44Z-score
OE missense 0.62 (0.570.68)
409 obs / 657.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.02 (0.010.11)
00.351.4
Missense OE0.62 (0.570.68)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 1 / 42.5Missense obs/exp: 409 / 657.0Syn Z: 0.57
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedNRXN3-related autismLOFAD
DN
0.4388th %ile
GOF
0.4776th %ile
LOF
0.66top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.11

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NRXN3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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