GeneBe

LGR5

protein-coding

leucine rich repeat containing G protein-coupled receptor 5, the group of G protein-coupled receptors, Class A orphans

Gene summary

The protein encoded by this gene is a leucine-rich repeat-containing receptor (LGR) and member of the G protein-coupled, 7-transmembrane receptor (GPCR) superfamily. The encoded protein is a receptor for R-spondins and is involved in the canonical Wnt signaling pathway. This protein plays a role in the formation and maintenance of adult intestinal stem cells during postembryonic development. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

Previous symbols:
  • GPR67
  • GPR49

MANE transcript

NM_003667.4

Inheritance

—

ClinVar variants

U:120B:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr12:71,439,798-71,586,310

External References & Databases

Ensembl (ENSG00000139292)NCBI Gene (8549)OMIM (606667)HGNC:4504GenCCUniProt (O75473)AlphaFoldClinVar (LGR5)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~146.5 kb
Loading mutation effect viewer...

GenCC 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 LGR5 variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 117
not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003667.4. 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
5
clinvar
1
clinvar
 8
missense
110
clinvar
7
clinvar
2
clinvar
 119
nonsense
2
clinvar
 2
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
6
clinvar
 6
Total00120123135
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_003667.4RefSeqNP_003658.118MANE Select
ENST00000266674.10EnsemblENSP00000266674.418MANE Select
NM_001277226.2RefSeqNP_001264155.117Standard
NM_001277227.2RefSeqNP_001264156.117Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Signaling by WNT
  • Signal Transduction
  • Regulation of FZD by ubiquitination
  • TCF dependent signaling in response to WNT

Biological Process

  • hair follicle development
  • G protein-coupled receptor signaling pathway
  • adenylate cyclase-activating G protein-coupled receptor signaling pathway
  • activation of adenylate cyclase activity
  • hormone-mediated signaling pathway

Molecular Function

  • transmembrane signaling receptor activity
  • G protein-coupled receptor activity
  • protein binding
  • G protein-coupled peptide receptor activity
  • protein-hormone receptor activity

Cellular Component

  • plasma membrane
  • integral component of plasma membrane
  • trans-Golgi network membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000266674
Coding exons
18
Length
146541
Individuals with no LoFs
125685
Homozygous LoFs
0
Heterozygous LoFs
63
Defined
125748
p
0.000251
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.1444744651.020.00002355890
Missense (PolyPhen)142175.090.810992387
Synonymous-0.2991971921.030.00001051825
Loss of Function2.921938.50.4930.00000182496

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000250.00025rare
Latino/Admixed American0.000290.00029rare
Ashkenazi Jewish0.0000990.000099rare
East Asian0.000160.00016rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.000330.00033rare
South Asian0.000230.00023rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and acts as a stem cell marker of the intestinal epithelium and the hair follicle. 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. Involved in the development and/or maintenance of the adult intestinal stem cells during postembryonic development. {ECO:0000269|PubMed:21693646, ECO:0000269|PubMed:21727895, ECO:0000269|PubMed:21909076, ECO:0000269|PubMed:22815884, ECO:0000269|PubMed:23809763}.;

Recessive Scores

pRec
0.141

Intolerance Scores

LoFtool
0.396
RVIS EVS
1.56
RVIS percentile EVS
95.68

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.621

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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