The protein encoded by this gene is a G-protein coupled receptor that binds R-spondins and activates the Wnt signaling pathway. This Wnt signaling pathway activation is necessary for proper development of many organs of the body. [provided by RefSeq, Oct 2016] See more...

Aliases for LGR4 Gene

Aliases for LGR4 Gene

  • Leucine Rich Repeat Containing G Protein-Coupled Receptor 4 2 3 5
  • Leucine-Rich Repeat-Containing G-Protein Coupled Receptor 4 3 4
  • G Protein-Coupled Receptor 48 2 3
  • GPR48 3 4
  • G-Protein Coupled Receptor 48 4
  • BNMD17 3
  • LGR4 5

External Ids for LGR4 Gene

Previous HGNC Symbols for LGR4 Gene

  • GPR48

Previous GeneCards Identifiers for LGR4 Gene

  • GC11M027084

Summaries for LGR4 Gene

Entrez Gene Summary for LGR4 Gene

  • The protein encoded by this gene is a G-protein coupled receptor that binds R-spondins and activates the Wnt signaling pathway. This Wnt signaling pathway activation is necessary for proper development of many organs of the body. [provided by RefSeq, Oct 2016]

GeneCards Summary for LGR4 Gene

LGR4 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 4) is a Protein Coding gene. Diseases associated with LGR4 include Bone Mineral Density Quantitative Trait Locus 17 and Anterior Segment Dysgenesis. Among its related pathways are Signaling by GPCR and Signaling by Wnt. Gene Ontology (GO) annotations related to this gene include G protein-coupled receptor activity and transmembrane signaling receptor activity. An important paralog of this gene is LGR5.

UniProtKB/Swiss-Prot Summary for LGR4 Gene

  • Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and is involved in the formation of various organs. 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. Its function as activator of the Wnt signaling pathway is required for the development of various organs, including liver, kidney, intestine, bone, reproductive tract and eye. May also act as a receptor for norrin (NDP), such results however require additional confirmation in vivo. Required during spermatogenesis to activate the Wnt signaling pathway in peritubular myoid cells. Required for the maintenance of intestinal stem cells and Paneth cell differentiation in postnatal intestinal crypts. Acts as a regulator of bone formation and remodeling. Involved in kidney development; required for maintaining the ureteric bud in an undifferentiated state. Involved in the development of the anterior segment of the eye. Required during erythropoiesis. Also acts as a negative regulator of innate immunity by inhibiting TLR2/TLR4 associated pattern-recognition and proinflammatory cytokine production. Plays an important role in regulating the circadian rhythms of plasma lipids, partially through regulating the rhythmic expression of MTTP (By similarity).

Gene Wiki entry for LGR4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for LGR4 Gene

Genomics for LGR4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for LGR4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around LGR4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for LGR4

Top Transcription factor binding sites by QIAGEN in the LGR4 gene promoter:
  • E2F
  • E2F-1
  • E2F-2
  • E2F-3a
  • E2F-4
  • E2F-5
  • HEN1
  • Nkx3-1
  • Nkx3-1 v1
  • Nkx3-1 v4

Genomic Locations for LGR4 Gene

Genomic Locations for LGR4 Gene
chr11:27,365,961-27,472,790
(GRCh38/hg38)
Size:
106,830 bases
Orientation:
Minus strand
chr11:27,387,508-27,494,334
(GRCh37/hg19)
Size:
106,827 bases
Orientation:
Minus strand

Genomic View for LGR4 Gene

Genes around LGR4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
LGR4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for LGR4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for LGR4 Gene

Proteins for LGR4 Gene

  • Protein details for LGR4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BXB1-LGR4_HUMAN
    Recommended name:
    Leucine-rich repeat-containing G-protein coupled receptor 4
    Protein Accession:
    Q9BXB1
    Secondary Accessions:
    • A6NCH3
    • G5E9B3
    • Q8N537
    • Q9NYD1

    Protein attributes for LGR4 Gene

    Size:
    951 amino acids
    Molecular mass:
    104475 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for LGR4 Gene

    Alternative splice isoforms for LGR4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for LGR4 Gene

Post-translational modifications for LGR4 Gene

  • Glycosylation at Asn68, Asn199, Asn294, Asn314, and Asn505
  • Modification sites at PhosphoSitePlus

Other Protein References for LGR4 Gene

No data available for DME Specific Peptides for LGR4 Gene

Domains & Families for LGR4 Gene

Gene Families for LGR4 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Disease related genes
  • G-protein coupled receptors
  • Potential drug targets
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for LGR4 Gene

InterPro:
Blocks:
  • Cysteine-rich flanking region, N-terminal
  • Glycoprotein hormone receptor signature
ProtoNet:

Suggested Antigen Peptide Sequences for LGR4 Gene

GenScript: Design optimal peptide antigens:
  • G-protein coupled receptor 48 (LGR4_HUMAN)
  • LGR4 protein (Q8N537_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9BXB1

UniProtKB/Swiss-Prot:

LGR4_HUMAN :
  • Belongs to the G-protein coupled receptor 1 family.
Family:
  • Belongs to the G-protein coupled receptor 1 family.
genes like me logo Genes that share domains with LGR4: view

Function for LGR4 Gene

Molecular function for LGR4 Gene

UniProtKB/Swiss-Prot Function:
Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and is involved in the formation of various organs. 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. Its function as activator of the Wnt signaling pathway is required for the development of various organs, including liver, kidney, intestine, bone, reproductive tract and eye. May also act as a receptor for norrin (NDP), such results however require additional confirmation in vivo. Required during spermatogenesis to activate the Wnt signaling pathway in peritubular myoid cells. Required for the maintenance of intestinal stem cells and Paneth cell differentiation in postnatal intestinal crypts. Acts as a regulator of bone formation and remodeling. Involved in kidney development; required for maintaining the ureteric bud in an undifferentiated state. Involved in the development of the anterior segment of the eye. Required during erythropoiesis. Also acts as a negative regulator of innate immunity by inhibiting TLR2/TLR4 associated pattern-recognition and proinflammatory cytokine production. Plays an important role in regulating the circadian rhythms of plasma lipids, partially through regulating the rhythmic expression of MTTP (By similarity).

Phenotypes From GWAS Catalog for LGR4 Gene

Gene Ontology (GO) - Molecular Function for LGR4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004888 transmembrane signaling receptor activity IDA 21727895
GO:0004930 NOT G protein-coupled receptor activity TAS,IDA 22815884
GO:0005515 protein binding IEA,IPI 21727895
GO:0008528 G protein-coupled peptide receptor activity IBA 21873635
GO:0016500 protein-hormone receptor activity IEA --
genes like me logo Genes that share ontologies with LGR4: view
genes like me logo Genes that share phenotypes with LGR4: view

Animal Models for LGR4 Gene

MGI Knock Outs for LGR4:
  • Lgr4 Lgr4<tm1.1(cre/ERT2)Npa>
  • Lgr4 Lgr4<tm1.2Knis>
  • Lgr4 Lgr4<tm1(cre/ERT2)Cle>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LGR4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for LGR4 Gene

Localization for LGR4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for LGR4 Gene

Cell membrane. Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for LGR4 gene
Compartment Confidence
plasma membrane 5
extracellular 2
cytoskeleton 2
nucleus 2
mitochondrion 1
endoplasmic reticulum 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Centriolar satellite (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for LGR4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IBA,IDA 22815884
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with LGR4: view

Pathways & Interactions for LGR4 Gene

genes like me logo Genes that share pathways with LGR4: view

SIGNOR curated interactions for LGR4 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for LGR4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001649 osteoblast differentiation ISS --
GO:0001942 hair follicle development IEA --
GO:0002376 immune system process IEA --
GO:0007165 signal transduction IEA --
GO:0007186 G protein-coupled receptor signaling pathway IEA --
genes like me logo Genes that share ontologies with LGR4: view

Drugs & Compounds for LGR4 Gene

(4) Drugs for LGR4 Gene - From: DGIdb and IUPHAR

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
R-spondin-1 Pharma Agonist, Full agonist 0
R-spondin-2 Pharma Agonist, Full agonist 0
R-spondin-3 Pharma Agonist, Full agonist 0
R-spondin-4 Pharma Agonist, Full agonist 0
genes like me logo Genes that share compounds with LGR4: view

Transcripts for LGR4 Gene

mRNA/cDNA for LGR4 Gene

2 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LGR4

Alternative Splicing Database (ASD) splice patterns (SP) for LGR4 Gene

No ASD Table

Relevant External Links for LGR4 Gene

GeneLoc Exon Structure for
LGR4

Expression for LGR4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for LGR4 Gene

mRNA differential expression in normal tissues according to GTEx for LGR4 Gene

This gene is overexpressed in Pancreas (x4.6).

Protein differential expression in normal tissues from HIPED for LGR4 Gene

This gene is overexpressed in Liver (44.6) and Bone (15.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for LGR4 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for LGR4

SOURCE GeneReport for Unigene cluster for LGR4 Gene:

Hs.502176

mRNA Expression by UniProt/SwissProt for LGR4 Gene:

Q9BXB1-LGR4_HUMAN
Tissue specificity: Expressed in multiple steroidogenic tissues: placenta, ovary, testis and adrenal. Expressed also in spinal cord, thyroid, stomach, trachea, heart, pancreas, kidney, prostate and spleen.

Evidence on tissue expression from TISSUES for LGR4 Gene

  • Nervous system(4.7)
  • Liver(4.5)
  • Pancreas(4.5)
  • Kidney(3.2)
  • Intestine(3.2)
  • Skin(2.5)
  • Stomach(2.5)
  • Lung(2.5)
  • Heart(2.2)
  • Muscle(2.2)
  • Gall bladder(2.1)
  • Adrenal gland(2)
genes like me logo Genes that share expression patterns with LGR4: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for LGR4 Gene

Orthologs for LGR4 Gene

This gene was present in the common ancestor of animals.

Orthologs for LGR4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia LGR4 30 31
  • 99.18 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia LGR4 30 31
  • 90.61 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia LGR4 30 31
  • 90.25 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Lgr4 30
  • 89.34 (n)
Mouse
(Mus musculus)
Mammalia Lgr4 30 17 31
  • 89.31 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia LGR4 31
  • 87 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia LGR4 31
  • 86 (a)
OneToOne
Chicken
(Gallus gallus)
Aves LGR4 30 31
  • 78.24 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia LGR4 31
  • 82 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia lgr4 30
  • 71.23 (n)
Str.14297 30
Zebrafish
(Danio rerio)
Actinopterygii lgr4 30
  • 61.52 (n)
LGR4 31
  • 58 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta rk 31
  • 21 (a)
OneToMany
Species where no ortholog for LGR4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for LGR4 Gene

ENSEMBL:
Gene Tree for LGR4 (if available)
TreeFam:
Gene Tree for LGR4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for LGR4: view image

Paralogs for LGR4 Gene

(9) SIMAP similar genes for LGR4 Gene using alignment to 2 proteins:

  • LGR4_HUMAN
  • E9PK51_HUMAN
genes like me logo Genes that share paralogs with LGR4: view

Variants for LGR4 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for LGR4 Gene

LGR4_HUMAN-Q9BXB1
Genetic variations in LGR4 define the bone mineral density quantitative trait locus 17 (BMND17) [MIM:615311]. Variance in bone mineral density influences bone mass, contributes to size determination in the general population, and is a susceptibility factor for osteoporotic fractures.

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for LGR4 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
713249 Benign: not provided 27,368,475(-) C/T MISSENSE_VARIANT
719745 Benign: not provided 27,368,673(-) T/C MISSENSE_VARIANT
727021 Likely Benign: not provided 27,376,322(-) T/C SYNONYMOUS_VARIANT
730324 Benign: not provided 27,369,152(-) A/C
749514 Likely Benign: not provided 27,368,314(-) G/A SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for LGR4 Gene

Structural Variations from Database of Genomic Variants (DGV) for LGR4 Gene

Variant ID Type Subtype PubMed ID
esv3579454 CNV loss 25503493
nsv1070018 CNV deletion 25765185
nsv1121833 CNV deletion 24896259
nsv1134101 CNV deletion 24896259
nsv1143676 CNV deletion 24896259
nsv467782 CNV gain 19166990
nsv553914 CNV gain 21841781

Variation tolerance for LGR4 Gene

Residual Variation Intolerance Score: 13.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.57; 72.29% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for LGR4 Gene

Human Gene Mutation Database (HGMD)
LGR4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
LGR4

SNP Genotyping and Copy Number Assay Products

Disorders for LGR4 Gene

MalaCards: The human disease database

(8) MalaCards diseases for LGR4 Gene - From: OMIM, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
bone mineral density quantitative trait locus 17
  • bone mineral density, low
anterior segment dysgenesis
  • anterior segment mesenchymal dysgenesis
biliary tract cancer
thyroid malformation
exposure keratitis
  • exposure keratoconjunctivitis
- elite association - COSMIC cancer census association via MalaCards
Search LGR4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

LGR4_HUMAN
  • Osteoporosis (OSTEOP) [MIM:166710]: A systemic skeletal disorder characterized by decreased bone mass and deterioration of bone microarchitecture without alteration in the composition of bone. The result is fragile bones and an increased risk of fractures, even after minimal trauma. Osteoporosis is a chronic condition of multifactorial etiology and is usually clinically silent until a fracture occurs. {ECO:0000269 PubMed:23644456}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry. A LGR4 nonsense mutation creating a stop codon after position 126 (c.376C>T) is strongly associated with low bone mineral density and osteoporotic fractures (PubMed:23644456). This mutation probably causes degradation of the transcript by nonsense-mediated decay (NMD). The c.376C>T mutation is also associated with electrolyte imbalance, late onset of menarche and reduced testosterone levels, as well as an increased risk of squamous cell carcinoma of the skin and biliary tract cancer (PubMed:23644456). {ECO:0000269 PubMed:23644456}.
genes like me logo Genes that share disorders with LGR4: view

No data available for Genatlas for LGR4 Gene

Publications for LGR4 Gene

  1. Chromosomal localization of GPR48, a novel glycoprotein hormone receptor like GPCR, in human and mouse with radiation hybrid and interspecific backcross mapping. (PMID: 10894923) Loh ED … Kolakowski LF (Cytogenetics and cell genetics 2000) 2 3 23
  2. Nonsense mutation in the LGR4 gene is associated with several human diseases and other traits. (PMID: 23644456) Styrkarsdottir U … Stefansson K (Nature 2013) 3 4
  3. Multi-functional norrin is a ligand for the LGR4 receptor. (PMID: 23444378) Deng C … Hsueh AJ (Journal of cell science 2013) 3 4
  4. R-Spondin potentiates Wnt/β-catenin signaling through orphan receptors LGR4 and LGR5. (PMID: 22815884) Ruffner H … Cong F (PloS one 2012) 3 4
  5. R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling. (PMID: 21693646) Carmon KS … Liu Q (Proceedings of the National Academy of Sciences of the United States of America 2011) 3 4

Products for LGR4 Gene

  • Signalway Proteins for LGR4

Sources for LGR4 Gene