ADGRL2
protein-codingadhesion G protein-coupled receptor L2, the group of Adhesion G protein-coupled receptors, subfamily L
Gene summary
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]
- LPHH1
- LPHN2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~687.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ADGRL2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001366006.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 11 | 3 | 14 | |||
| missense | 149 | 8 | 6 | 163 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 157 | 19 | 9 | 185 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001352935.1 | 23 | MANE Select | |
| Ensembl | ENSP00000509478.1 | 23 | MANE Select | |
| RefSeq | NP_001284633.1 | 19 | Standard | |
| RefSeq | NP_001284634.1 | 20 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- GPCRs, Other
- GPCRs, Class B Secretin-like
Biological Process
- cell surface receptor signaling pathway
- G protein-coupled receptor signaling pathway
- adenylate cyclase-activating G protein-coupled receptor signaling pathway
- brain development
Molecular Function
- G protein-coupled receptor activity
- latrotoxin receptor activity
- carbohydrate binding
Cellular Component
- integral component of plasma membrane
- integral component of membrane
- neuron projection
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000319517
- Coding exons
- 19
- Length
- 686276
- Individuals with no LoFs
- 125728
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125745
- p
- 0.0000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.22 | 647 | 741 | 0.873 | 0.0000383 | 9215 |
| Missense (PolyPhen) | 261 | 349.46 | 0.74686 | 4363 | ||
| Synonymous | -0.552 | 282 | 270 | 1.04 | 0.0000149 | 2692 |
| Loss of Function | 7.33 | 3 | 68.5 | 0.0438 | 0.00000420 | 775 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00013 | 0.00012 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000056 | 0.000054 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000063 | 0.000062 | rare |
| South Asian | 0.000040 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Calcium-independent receptor of low affinity for alpha- latrotoxin, an excitatory neurotoxin present in black widow spider venom which triggers massive exocytosis from neurons and neuroendocrine cells. Receptor probably implicated in the regulation of exocytosis. {ECO:0000250|UniProtKB:O88923}.;
Recessive Scores
- pRec
- 0.262
Intolerance Scores
- RVIS EVS
- -0.19
- RVIS percentile EVS
- 39.31
Essentials
- Essential (gene trap)
- N