LGR5

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

Basic information

Region (hg38): 12:71439797-71586310

Previous symbols: [ "GPR67", "GPR49" ]

Links

ENSG00000139292 ∙ NCBI:8549 ∙ OMIM:606667 ∙ HGNC:4504 ∙ Uniprot:O75473 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LGR5 gene.

• Inborn genetic diseases (32 variants)
• not provided (9 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LGR5 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	1	3
missense			31	4	2	37
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	31	6	3

Variants in LGR5

This is a list of pathogenic ClinVar variants found in the LGR5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-71440117-C-A		not specified	Uncertain significance (Jul 19, 2023)
12-71440214-G-A		not specified	Uncertain significance (Jul 09, 2021)
12-71504624-A-G		not specified	Uncertain significance (Sep 25, 2023)
12-71504657-C-A		not specified	Uncertain significance (Dec 01, 2022)
12-71504658-T-G		not specified	Uncertain significance (Jan 02, 2024)
12-71504663-A-T		not specified	Uncertain significance (Jan 16, 2024)
12-71524406-A-G		not specified	Likely benign (Aug 21, 2023)
12-71535142-C-T			Likely benign (Jun 12, 2018)
12-71535175-C-A		not specified	Uncertain significance (Feb 02, 2024)
12-71535176-C-T		not specified	Uncertain significance (Oct 06, 2023)
12-71553092-A-C		not specified	Uncertain significance (Jun 29, 2022)
12-71553245-A-T		not specified	Uncertain significance (Mar 29, 2022)
12-71553284-G-A		not specified	Uncertain significance (Sep 27, 2021)
12-71556627-A-G			Likely benign (Aug 01, 2018)
12-71556628-T-G		not specified	Uncertain significance (Dec 09, 2023)
12-71556630-A-C		not specified	Uncertain significance (Dec 09, 2023)
12-71556642-A-G		not specified	Uncertain significance (Oct 03, 2022)
12-71566905-C-G		not specified	Uncertain significance (Dec 12, 2022)
12-71572858-G-A		not specified	Uncertain significance (Oct 27, 2023)
12-71572861-A-G			Likely benign (Jun 08, 2018)
12-71577963-A-G		not specified	Uncertain significance (Aug 02, 2022)
12-71577986-C-G			Benign (Jun 15, 2018)
12-71578805-G-A			Benign (Jun 08, 2018)
12-71578813-G-T			Benign (Jun 15, 2018)
12-71578827-C-T			Likely benign (Feb 16, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LGR5	protein_coding	protein_coding	ENST00000266674	18	146541

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.50e-8	0.999	125685	0	63	125748	0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.144	474	465	1.02	0.0000235	5890
Missense in Polyphen		142	175.09	0.81099		2387
Synonymous	-0.299	197	192	1.03	0.0000105	1825
Loss of Function	2.92	19	38.5	0.493	0.00000182	496

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000537	0.000536
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000327	0.000325
Middle Eastern	0.000163	0.000163
South Asian	0.000229	0.000229
Other	0.00	0.00

dbNSFP

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}.
• Pathway: Signaling by WNT;Signal Transduction;Regulation of FZD by ubiquitination;TCF dependent signaling in response to WNT (Consensus)

Recessive Scores

• pRec: 0.141

Intolerance Scores

• loftool: 0.396
• rvis_EVS: 1.56
• rvis_percentile_EVS: 95.68

Haploinsufficiency Scores

• pHI: 0.639
• hipred: Y
• hipred_score: 0.591
• ghis: 0.403

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.621

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lgr5
• Phenotype: renal/urinary system phenotype; digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype

Gene ontology

• 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;oocyte differentiation;regulation of cell population proliferation;inner ear development;positive regulation of canonical Wnt signaling pathway;epithelial cell proliferation involved in renal tubule morphogenesis
• Cellular component: plasma membrane;integral component of plasma membrane;trans-Golgi network membrane
• Molecular function: transmembrane signaling receptor activity;G protein-coupled receptor activity;protein binding;G protein-coupled peptide receptor activity;protein-hormone receptor activity