LGR6
protein-codingleucine rich repeat containing G protein-coupled receptor 6, the group of G protein-coupled receptors, Class A orphans
Gene summary
This gene encodes a member of the leucine-rich repeat-containing subgroup of the G protein-coupled 7-transmembrane protein superfamily. The encoded protein is a glycoprotein hormone receptor with a large N-terminal extracellular domain that contains leucine-rich repeats important for the formation of a horseshoe-shaped interaction motif for ligand binding. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~126.0 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 LGR6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001017403.2. 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 | 3 | 5 | 2 | 10 | ||
| missense | 140 | 6 | 1 | 147 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 146 | 11 | 3 | 160 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001017403.1 | 18 | MANE Select | |
| Ensembl | ENSP00000356247.3 | 18 | MANE Select | |
| RefSeq | NP_001017404.1 | 16 | Standard | |
| RefSeq | NP_067649.2 | 18 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- GPCRs, Other
- Signaling by WNT
- Signal Transduction
- Regulation of FZD by ubiquitination
- TCF dependent signaling in response to WNT
Biological Process
- G protein-coupled receptor signaling pathway
- Wnt signaling pathway
- positive regulation of Wnt signaling pathway
- positive regulation of cell migration
- positive regulation of canonical Wnt signaling pathway
Molecular Function
- transmembrane signaling receptor activity
- G protein-coupled receptor activity
- protein binding
- protein-hormone receptor activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- vesicle
- trans-Golgi network membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000367278
- Coding exons
- 18
- Length
- 125881
- Individuals with no LoFs
- 125708
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 40
- Defined
- 125748
- p
- 0.000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.07 | 482 | 553 | 0.872 | 0.0000320 | 6143 |
| Missense (PolyPhen) | 170 | 223.76 | 0.75975 | 2606 | ||
| Synonymous | 0.496 | 245 | 255 | 0.960 | 0.0000155 | 2105 |
| Loss of Function | 3.31 | 16 | 38.0 | 0.421 | 0.00000177 | 431 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00022 | 0.00020 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00015 | 0.00015 | rare |
| South Asian | 0.00043 | 0.00042 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and acts as a marker of multipotent stem cells in the epidermis. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. In contrast to classical G-protein coupled receptors, does not activate heterotrimeric G-proteins to transduce the signal. May act as a tumor suppressor. {ECO:0000269|PubMed:21727895, ECO:0000269|PubMed:22615920}.;
Intolerance Scores
- LoFtool
- 0.232
- RVIS EVS
- -0.1
- RVIS percentile EVS
- 45.69
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0700
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |