ADGRL2

Chr 1

adhesion G protein-coupled receptor L2

Also known as: CIRL2, CL2, LEC1, LPHH1, LPHN2

NCBI Gene: 23266ENSG00000117114UniProt: O95490

This gene encodes a member of the latrophilin subfamily of G-protein coupled receptors. The encoded protein participates in the regulation of exocytosis. The proprotein is thought to be further cleaved within a cysteine-rich G-protein-coupled receptor proteolysis site into two chains that are non-covalently bound at the cell membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

Research Assistant →
0
Active trials
11
Pubs (1 yr)
15
P/LP submissions
0%
P/LP missense
0.11
LOEUF· LoF intol.
—
Mechanism
Clinical Summary— ADGRL2
⚡
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.
📋
ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 148 VUS of 220 total submissions
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
0.11LOEUF
pLI 1.000
Z-score 7.33
OE 0.04 (0.02–0.11)
Highly constrained

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

Missense Constraint
1.22Z-score
OE missense 0.87 (0.82–0.93)
647 obs / 740.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.04 (0.02–0.11)
0≤0.351.4
Missense OE0.87 (0.82–0.93)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 3 / 68.5Missense obs/exp: 647 / 740.7Syn Z: -0.55

ClinVar Variant Classifications

220 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic2
VUS148
Likely Benign21
Benign16
13
Pathogenic
2
Likely Pathogenic
148
VUS
21
Likely Benign
16
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
2
0
2
VUS
0
145
3
0
148
Likely Benign
0
7
3
11
21
Benign
0
8
2
6
16
Total01602317200

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

View in ClinVar →

Protein Context — Lollipop Plot

ADGRL2 · 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.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors.
Hamann J et al.·Pharmacol Rev
2015Review
A correlation study of adhesion G protein-coupled receptors as potential therapeutic targets in Uterine Corpus Endometrial cancer.
Lei P et al.·Int Immunopharmacol
2022
A de novo variant in ADGRL2 suggests a novel mechanism underlying the previously undescribed association of extreme microcephaly with severely reduced sulcation and rhombencephalosynapsis.
Vezain M et al.·Acta Neuropathol Commun
2018Functional
Genetic Architecture of Adaptive Immune System Identifies Key Immune Regulators.
Lagou V et al.·Cell Rep
2018
Pontocerebellar hypoplasia with rhombencephalosynapsis and microlissencephaly expands the spectrum of PCH type 1B.
Saugier-Veber P et al.·Eur J Med Genet
2020Case report
Top 5 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