ADGRL2

Chr 1

adhesion G protein-coupled receptor L2

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

NCBI Gene: 23266 ENSG00000117114 UniProt: O95490 OMIM: 607018

The protein is an adhesion G-protein coupled receptor that mediates synapse specificity by associating with cell adhesion molecules to direct synapse formation, particularly in hippocampal perforant-path synapses. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and autism spectrum features. This gene is highly constrained against loss-of-function variants, indicating that such variants are likely to be pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

—

Mechanism

Some data sources returned errors (1)

gnomad: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in ADGRL2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 37

1,769 rare PASS variants

Rare truncating (LoF)

1 in 1,100

140 rare PASS variants

Rare synonymous (reference)

1 in 67

662 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ADGRL2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 44	1 in 1,300
South Asian	~43k	1 in 30	1 in 590
Remaining (unassigned)	~30k	1 in 33	1 in 1,300
European (Finnish)	~27k	1 in 100	≈ 1 in 13,000
Admixed American	~22k	1 in 34	1 in 910
African / African American	~21k	1 in 32	1 in 530
East Asian	~20k	1 in 47	1 in 1,000
Ashkenazi Jewish	~13k	1 in 130	1 in 600
Middle Eastern	~2,884	1 in 39	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 14 of 23 coding exons well covered in gnomAD exomes; exons 5, 23 poorly covered; exons 2, 4, 8, 10, 16 and 2 more marginal. Genomes: all 23.? see exons ↓