ADGRL1

Chr 19AD

adhesion G protein-coupled receptor L1

Also known as: CIRL1, CL1, DEDBANP, LEC2, LPHN1

NCBI Gene: 22859 ENSG00000072071 UniProt: O94910 OMIM: 616416

ADGRL1 encodes latrophilin-1, a G-protein coupled receptor that serves as a calcium-independent receptor for alpha-latrotoxin and mediates synaptic cell-cell contact and regulation of exocytosis at synapses. Mutations cause autosomal dominant developmental delay with behavioral abnormalities and neuropsychiatric disorders. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.19), indicating intolerance to functional disruption.

OMIM ResearchSummary from RefSeq, OMIM, 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. Latrophilin-1 has been shown to recruit the neurotoxin from black widow spider venom, alpha-latrotoxin, to the synapse plasma membrane. Alternative splicing results in multiple variants encoding distinct isoforms.[provided by RefSeq, Oct 2008]

OMIM ResearchGenerating clinical summary…

ADLOEUF 0.191 OMIM phenotype

Clinical Summary— ADGRL1

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

32 unique Pathogenic / Likely Pathogenic· 252 VUS of 370 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.19LOEUF

pLI 1.000

Z-score 6.99

OE 0.10 (0.06–0.19)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.43Z-score

OE missense 0.68 (0.64–0.73)

640 obs / 934.8 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.10 (0.06–0.19)

0≤0.351.4

Missense OE?0.68 (0.64–0.73)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 7 / 70.3Missense obs/exp: 640 / 934.8Syn Z: -1.72

ClinVar Variant Classifications

370 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16

Likely Pathogenic16

VUS252

Likely Benign51

Benign1

Conflicting5

Pathogenic

Likely Pathogenic

252

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	13	3	0	0	16
Likely Pathogenic	13	3	0	0	16
VUS	3	245	3	1	252
Likely Benign	0	14	4	33	51
Benign	0	0	0	1	1
Conflicting	—				5
Total	29	265	7	35	341

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap ADGRL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →