LGI3

Chr 8AR

leucine rich repeat LGI family member 3

Also known as: IDDMDS, LGIL4

NCBI Gene: 203190ENSG00000168481UniProt: Q8N145

Predicted to be involved in regulation of exocytosis. Located in extracellular space. [provided by Alliance of Genome Resources, Jul 2025]

Research Assistant →

Primary Disease Associations & Inheritance

Intellectual developmental disorder with muscle tone abnormalities and distal skeletal defectsMIM #620007
AR
0
Active trials
2
Pubs (1 yr)
34
P/LP submissions
0%
P/LP missense
0.77
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— LGI3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
34 unique Pathogenic / Likely Pathogenic· 71 VUS of 121 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.77LOEUF
pLI 0.000
Z-score 2.44
OE 0.48 (0.30–0.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.49Z-score
OE missense 0.92 (0.84–1.02)
308 obs / 333.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.48 (0.30–0.77)
0≤0.351.4
Missense OE0.92 (0.84–1.02)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 12 / 25.2Missense obs/exp: 308 / 333.2Syn Z: -0.22
DN
0.74top 25%
GOF
0.6833th %ile
LOF
0.3065th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

121 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic1
VUS71
Likely Benign5
Benign4
33
Pathogenic
1
Likely Pathogenic
71
VUS
5
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
33
0
33
Likely Pathogenic
0
0
1
0
1
VUS
1
64
5
1
71
Likely Benign
0
0
0
5
5
Benign
0
2
0
2
4
Total166398114

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LGI3 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients