ADGRL3

Chr 4

adhesion G protein-coupled receptor L3

Also known as: CIRL3, CL3, LEC3, LPHN3

NCBI Gene: 23284ENSG00000150471UniProt: Q9HAR2

This gene encodes a member of the latrophilin subfamily of G-protein coupled receptors (GPCR). Latrophilins may function in both cell adhesion and signal transduction. In experiments with non-human species, endogenous proteolytic cleavage within a cysteine-rich GPS (G-protein-coupled-receptor proteolysis site) domain resulted in two subunits (a large extracellular N-terminal cell adhesion subunit and a subunit with substantial similarity to the secretin/calcitonin family of GPCRs) being non-covalently bound at the cell membrane. [provided by RefSeq, Jul 2008]

0
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— ADGRL3
⚡
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

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.18LOEUF
pLI 1.000
Z-score 6.73
OE 0.09 (0.05–0.18)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
2.67Z-score
OE missense 0.73 (0.68–0.79)
578 obs / 788.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.09 (0.05–0.18)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.68–0.79)
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.1.01
0≤1.21.6
LoF obs/exp: 6 / 64.1Missense obs/exp: 578 / 788.9Syn Z: -0.19

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ADGRL3 · 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
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Discovery of Novel Pyrano[3,2-a]carbazole Alkaloid Derivatives against Ischemic Stroke by Targeting ADGRL3.
Tao A et al.·J Med Chem
2026
Gene × environment interaction between latrophilin-3 (Lphn3 or Adgrl3) and developmental permethrin exposure in Sprague Dawley rats.
Vorhees CV et al.·Neurotoxicol Teratol
2026
Genome sequencing reveals the Adgrl3 (ADGRL3) gene as a possible cause of cephalic hypersensitivity in the STA rat and migraine in humans.
Nielsen BS et al.·Cephalalgia
2025
Expression profile of the ADHD risk gene ADGRL3 during human neurodevelopment and the effects of genetic variation.
McNeill RV et al.·World J Biol Psychiatry
2025
Gene × environment interaction between heterozygous deletion of the ADHD risk gene latrophilin-3 (adgrl3) and developmental deltamethrin exposure in Sprague Dawley rats.
Vorhees CV et al.·Neurotoxicol Teratol
2025
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