ADGRL3
protein-codingadhesion G protein-coupled receptor L3, 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 (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]
- LPHN3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~878.0 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 ADGRL3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001387552.1. 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 | 4 | 2 | 6 | |||
| missense | 149 | 1 | 150 | |||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 160 | 4 | 0 | 164 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001374481.1 | 25 | MANE Select | |
| Ensembl | ENSP00000507980.1 | 25 | MANE Select | |
| RefSeq | NP_001309175.1 | 24 | Standard | |
| RefSeq | NP_001309331.1 | 24 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| adgrl3.1 | Danio rerio | Structure: whole organism Quality: increased behavioural activity abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- GPCRs, Other
- GPCRs, Class B Secretin-like
Biological Process
- neuron migration
- cell surface receptor signaling pathway
- G protein-coupled receptor signaling pathway
- adenylate cyclase-activating G protein-coupled receptor signaling pathway
- synapse assembly
Molecular Function
- G protein-coupled receptor activity
- calcium ion binding
- protein binding
- carbohydrate binding
Cellular Component
- integral component of plasma membrane
- cell-cell junction
- integral component of membrane
- axon
- glutamatergic synapse
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000514591
- Coding exons
- 23
- Length
- 877078
- Individuals with no LoFs
- 124788
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 124797
- p
- 0.0000361
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.67 | 578 | 789 | 0.733 | 0.0000417 | 9609 |
| Missense (PolyPhen) | 223 | 385.83 | 0.57797 | 4853 | ||
| Synonymous | -0.189 | 301 | 297 | 1.01 | 0.0000163 | 2869 |
| Loss of Function | 6.73 | 6 | 64.1 | 0.0935 | 0.00000344 | 797 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000088 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000046 | 0.000044 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in cell-cell adhesion and neuron guidance via its interactions with FLRT2 and FLRT3 that are expressed at the surface of adjacent cells (PubMed:26235030). Plays a role in the development of glutamatergic synapses in the cortex. Important in determining the connectivity rates between the principal neurons in the cortex. {ECO:0000250|UniProtKB:Q80TS3, ECO:0000305|PubMed:26235030}.;
Recessive Scores
- pRec
- 0.141
Intolerance Scores
- RVIS EVS
- -0.37
- RVIS percentile EVS
- 28.26