ADGRL3

Chr 4

adhesion G protein-coupled receptor L3

Also known as: CIRL3, CL3, LEC3, LPHN3

NCBI Gene: 23284 ENSG00000150471 UniProt: Q9HAR2 OMIM: 616417

This gene encodes an adhesion G-protein coupled receptor that mediates synapse specificity and promotes glutamatergic synapse formation, particularly in the hippocampus and cortex. Mutations cause autosomal dominant neurodevelopmental disorders including intellectual disability and attention deficit hyperactivity disorder. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOEUF 0.18

Clinical Summary— ADGRL3

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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.

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ClinVar Variants

144 VUS of 174 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.09 (0.05–0.18)

0≤0.351.4

Missense OE?0.73 (0.68–0.79)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 6 / 64.1Missense obs/exp: 578 / 788.9Syn Z: -0.19

ClinVar Variant Classifications

174 submitted variants in ClinVar

ClinVar

Classification Summary

VUS144

Likely Benign3

144

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	143	1	0	144
Likely Benign	1	0	2	3
Benign	0	0	0	0
Total	144	1	2	147

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap ADGRL3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →