Property Summary

NCBI Gene PubMed Count 37
PubMed Score 81.19
PubTator Score 72.95

Knowledge Summary

Patent (6,865)


  Disease (3)

Disease Target Count
Cryptorchidism 67
Disease Target Count P-value
psoriasis 6685 1.1e-06
Disease Target Count Z-score Confidence
Testicular cancer 24 3.791 1.9
Infertility 163 3.436 1.7


  Differential Expression (1)

Disease log2 FC p
psoriasis -2.100 1.1e-06

MLP Assay (2)

AID Type Active / Inconclusive / Inactive Description
489043 confirmatory 176 / 182 / 111 qHTS Assay for Agonists of the Relaxin Receptor RXFP1: RXFP2 Hit Validation
602258 confirmatory 5 / 7 / 55 qHTS Assay for Agonists of the Relaxin Receptor RXFP1: RXFP2 SAR

Gene RIF (34)

24983702 Mapping key regions of the RXFP2 low-density lipoprotein class-A module that are involved in signal activation.
23539510 Findings suggest a novel and gender-specific role for INSL3 and cognate receptor RXFP2 signaling in ocular surface homeostasis.
23024363 Identification of key residues essential for the structural fold and receptor selectivity within the A-chain of human gene-2 (H2) relaxin
22973049 These results provide new mechanistic insights into the binding and activation events of RXFP1 and RXFP2 by their native hormone ligands.
22737225 relaxin-2 and its receptors RXFP1 and RXFP2 are expressed in GSV and their expression is significantly decreased in varicose GSV
21789898 higher expression of LGR8 may facilitate tumor invasiveness in the early clinical stage of hepatocellular carcinoma.
20636340 haplotype analysis of the RXFP2 gene in T222P carriers and their parents showed that this variant is linked to the previously inferred C-C-G-A-13 haplotype and consequently provides further support to the 'founder effect' hypothesis
20636340 Observational study of gene-disease association. (HuGE Navigator)
20560146 Data show that synthetic parallel dimer of the B-chain of INSL3 is a potent inhibitor of the native peptide's binding to its receptor, RXFP2.
19416191 Data link RXFP2 gene mutations with human osteoporosis.
19416190 This study confirmed the association between INSL3 and RXFP2 gene mutations and human cryptorchidism.
19416190 Observational study of gene-disease association. (HuGE Navigator)
19416188 Several missense mutations were described in both the INSL3 and RXFP2 genes and a novel V39G INSL3 mutation in a patient with cryptorchidism was identified
19416162 relaxin binds with high affinity to the leucine-rich repeats of RXFP2 in a manner similar to INSL3 binding to its receptor
19416161 Ligand-mediated activation of RXFP1 and RXFP2 is a complex process involving various domains of the receptors
19279230 The apparent lack of classical regulation for RXFP1 and RXFP2 provides the molecular basis for the prolonged signaling and physiological actions of relaxin and related peptides
19017913 Observational study of gene-disease association. (HuGE Navigator)
18772597 No association between T222P/LGR8 mutation and cryptorchidism in the Moroccan population
18434306 analysis of truncated human relaxin-2 and -3 (H2 and H3) relaxin peptides and their binding and cAMP activities on RXFP1, RXFP2, and RXFP3
18073304 T222P mutation cannot be considered either causative or a susceptibility factor for cryptorchidism.
18073304 Observational study of gene-disease association. (HuGE Navigator)
18063691 negative cooperativity is present and that INSL3-RXFP2 binding shows both similarities and differences with insulin binding to the insulin receptor
17473281 predicted the complete INSL3/LGR8 primary binding site, including interactions between INSL3 His-B12 and LGR8 Trp-177, INSL3 Val-B19 and LGR8 Ile-179, and INSL3 Arg-B20 with LGR8 Asp-181 and Glu-229
17437853 The V18M mutation in the insulin-like factor 3 signal peptide had a significant deleterious effect in activating LGR8 receptor in ex vivo studies
17028442 Observational study of gene-disease association. (HuGE Navigator)
16963451 The essential role of the LDLa module in LGR7 and LGR8 function is reported.
16926383 Novel allele of LGR8 (R223K) found in one patient with retractile testes.
16867980 Alanine-substituted analogs were used to identify the key residues of INSL3 that are responsible for the interaction with the ectodomain of LGR8. These include Arg(B16) and Val(B19), with His(B12) and Arg(B20) playing a secondary role.
16051677 LGR8.1 spliced isoform is expressed at the cell surface, unable to stimulate cAMP production.
15708846 LGR8 signal is activated by the relaxin-like factor
15579790 recurrent T222P mutation in the LGR8 gene was not found in any of the patients. These data show for the first time a lack of association between genetic factors necessary for correct testicular descent and anorchia.
14656401 Observational study of gene-disease association. (HuGE Navigator)
14656401 mutations involving the human LGR8 gene do not represent a frequent cause of cryptorchidism in the Finnish population
12970298 the only clinical consequence of alterations of the INSL3-LGR8 system seems to be failure of the testis to normally descend in the scrotum during embryonic development, without affecting the spermatogenic and endocrine components of the testis itself

AA Sequence


Text Mined References (38)

PMID Year Title
24983702 2014 Mapping key regions of the RXFP2 low-density lipoprotein class-A module that are involved in signal activation.
23539510 2013 Insulin-like factor 3 promotes wound healing at the ocular surface.
23024363 2012 Identification of key residues essential for the structural fold and receptor selectivity within the A-chain of human gene-2 (H2) relaxin.
22973049 2012 The different ligand-binding modes of relaxin family peptide receptors RXFP1 and RXFP2.
22737225 2012 A novel role for relaxin-2 in the pathogenesis of primary varicosis.
21789898 2011 Expression of LGR8 and related biomarkers in hepatocellular carcinoma: correlation with clinicopathological parameters.
20636340 2011 Further insights into the role of T222P variant of RXFP2 in non-syndromic cryptorchidism in two Mediterranean populations.
20560146 2011 Design and development of analogues of dimers of insulin-like peptide 3 B-chain as high-affinity antagonists of the RXFP2 receptor.
19416191 2009 New roles for INSL3 in adults.
19416190 2009 Mutations in INSL3 and RXFP2 genes in cryptorchid boys.
19416188 2009 INSL3/RXFP2 signaling in testicular descent.
19416162 2009 Modeling the primary hormone-binding site of RXFP1 and RXFP2.
19416161 2009 Resolving the unconventional mechanisms underlying RXFP1 and RXFP2 receptor function.
19279230 2009 Prolonged RXFP1 and RXFP2 signaling can be explained by poor internalization and a lack of beta-arrestin recruitment.
19017913 2008 Genetic alterations associated with cryptorchidism.
18772597 2008 No association between T222P/LGR8 mutation and cryptorchidism in the Moroccan population.
18434306 2008 The A-chain of human relaxin family peptides has distinct roles in the binding and activation of the different relaxin family peptide receptors.
18073304 2008 The leucine-rich repeat-containing G protein-coupled receptor 8 gene T222P mutation does not cause cryptorchidism.
18063691 2008 Cooperative binding of insulin-like Peptide 3 to a dimeric relaxin family peptide receptor 2.
17473281 2007 Defining the LGR8 residues involved in binding insulin-like peptide 3.
17437853 2007 Novel mutations involving the INSL3 gene associated with cryptorchidism.
17028442 2007 Mutation and polymorphism analyses of INSL3 and LGR8/GREAT in 62 Japanese patients with cryptorchidism.
16963451 2006 Characterization of novel splice variants of LGR7 and LGR8 reveals that receptor signaling is mediated by their unique low density lipoprotein class A modules.
16926383 2007 T222P mutation of the insulin-like 3 hormone receptor LGR8 is associated with testicular maldescent and hinders receptor expression on the cell surface membrane.
16867980 2006 Solution structure and characterization of the LGR8 receptor binding surface of insulin-like peptide 3.
16507880 2006 International Union of Pharmacology LVII: recommendations for the nomenclature of receptors for relaxin family peptides.
16051677 2005 Splice variants of the relaxin and INSL3 receptors reveal unanticipated molecular complexity.
15956688 2005 Receptors for relaxin family peptides.
15708846 2005 LGR8 signal activation by the relaxin-like factor.
15579790 2004 An analysis of the genetic factors involved in testicular descent in a cohort of 14 male patients with anorchia.
15057823 2004 The DNA sequence and analysis of human chromosome 13.
14656401 Lack of LGR8 gene mutation in Finnish patients with a family history of cryptorchidism.
12970298 2003 The INSL3-LGR8/GREAT ligand-receptor pair in human cryptorchidism.
12506116 2003 H3 relaxin is a specific ligand for LGR7 and activates the receptor by interacting with both the ectodomain and the exoloop 2.
12217959 2002 Mutations of the GREAT gene cause cryptorchidism.
12114498 2002 INSL3/Leydig insulin-like peptide activates the LGR8 receptor important in testis descent.
12036966 2002 Selective inhibition of heterotrimeric Gs signaling. Targeting the receptor-G protein interface using a peptide minigene encoding the Galpha(s) carboxyl terminus.
11809971 2002 Activation of orphan receptors by the hormone relaxin.