Property Summary

NCBI Gene PubMed Count 99
PubMed Score 271.72
PubTator Score 196.57

Knowledge Summary


No data available


  Differential Expression (1)

Disease log2 FC p
osteosarcoma -1.271 1.2e-04

Gene RIF (76)

26625974 rs6523 polymorphism and AGAG haplotype of INSL3 showed significant association with increased risk of polycystic ovary syndrome.
26579638 Healthy eumenorrheic late adolescent females with sporadic anovulation display higher INSL3 blood concentration.
26077926 hINSL3 seems to recruit Aund spermatogonia into differentiation, potentially mediating an Fsh effect on spermatogenesis.
25728210 Three common INSL3 gene polymorphisms (27G>A, 126G>A, 178G>A) unrelated to any particular phenotype of testicular maldescent (TMD) were detected both in patients and controls, indicating that INSL3 gene mutations are not a common cause of TMD.
25516081 INSL3 in girls is a unique and specific marker of theca cells surrounding antral follicles.
24908673 DLK1, INSL3 and COUP-TFII expression changes during normal development and is linked to different stages of Leydig Cell differentiation.
24659579 low INSL3 concentration is related to the pathogenesis behind an unfavourable change in body composition and bone metabolism among Klinefelter syndrome patients
24640568 The aim of this study was to assess plasma INSL3 in patients with osteoporosis and Klinefelter's Syndrome compared to healthy males.
24243640 INSL3 is as sensitive a marker as T for the evaluation of altered Leydig cell function in congenital hypogonadotropic hypogonadism/Kallmann syndrome patients.
23928669 INSL3 and AMH levels are significantly correlated with each other in women with PCOS, and they are significantly increased, particularly in the presence of amenorrhea and oligomenorrhea.
23898208 HIV-1 Tat upregulates the expression of insulin-like 3 (INSL3) in human primary T cells
23539510 Findings suggest a novel and gender-specific role for INSL3 and cognate receptor RXFP2 signaling in ocular surface homeostasis.
23150680 Most Prader-Willi syndrome males have normal INSL3 levels.
23028900 In the meta-analysis, INSL3 rs10421916 and rs11088680 had both a 0.8-fold decreased odds ratio for gastric cancer.
22574850 Cystin A11-B10 serves as an insulator between the two ports, whereas the amide functionality disturbs the signal transmission complex likely due to changes in polarity.
22216350 study demonstrates that the INSL3/RXFP2 system is involved in bone metabolism by acting on the MAPK cascade and stimulating transcription of important genes of osteoblast maturation/differentiation and osteoclastogenesis
21586896 Data suggest that insulin-like factor 3 is related to functional ovarian hyperandrogenism in women with polycystic ovary syndrome.
20713036 The aim of the present study is to investigate the effect of obesity on testicular function by evaluating reproductive hormones, inhibinB, insulin-like 3(INSL3), and leptin, in obese and non-obese adolescents according to pubertal Tanner stages.
20570702 investigation of INSL3 structural requirements (i.e., intra-A-chain disulfide bonds) for binding to & activation of RXFP2
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.
20550598 The current knowledge of INSL3, its involvement in testicular descent and germ cell survival, verifies that this Leydig cell hormone is an important player in testicular physiology[review]
20438785 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20406964 Observational study of gene-disease association. (HuGE Navigator)
20200332 Observational study of gene-disease association. (HuGE Navigator)
20082125 Results describe the in vitro degradation of insulin-like peptide 3 by insulin-degrading enzyme.
19950223 INSL3 is a powerful and multifunctional promoter of tumor growth and angiogenesis in human thyroid cancer cell xenografts. INSL3 actions involve RXFP2 activation and the secretion of S100A4 and (pro-)cathepsin-L
19773279 Observational study of gene-disease association. (HuGE Navigator)
19755411 An early impairment of the overall Leydig cell function is present in men with T2DM, manifesting as reduced INSL3, mainly related to visceral adiposity rather than to glycemic control.
19423540 Observational study of gene-disease association. (HuGE Navigator)
19416220 Data provide the first evidence that the INSL3 peptide can promote early tumor cell invasiveness in human thyroid carcinoma cells by enhancing their metabolic activity and elastin-degrading potential.
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
19416166 The receptor-binding residues of RLF are in the B chain of the two-chain molecule and extend from the midregion of the central helix to the tryptophan in position B27
19329805 The role of INSL3 throughout human reproduction is discussed. [review]
19226271 This study showed for the first time that INSL3 levels decrease with obesity, probably as a result of a primary dysfunction of the Leydig cells. INSL3 is a reliable marker of Leydig cell general impairment.
19110449 High INSL3 is associated with testicular Leydig cell tumors.
19086273 Via comparison of the solution structure of a fully active carboxy-terminal cross-linked RLF analogue with the native synthetic human RLF, it becomes clear that the cross-linked analogue largely retains the essential folding of the native protein.
19067106 Analogues of INSL3 with higher alpha-helicity had higher receptor binding affinity.
19017913 There is a significant association between bilateral and persistent cryptorchidism and genetic alterations, including Klinefelter syndrome and INSL3 receptor gene mutations.
19017913 Observational study of gene-disease association. (HuGE Navigator)
18772597 Observational study of gene-disease association. (HuGE Navigator)
18611973 INSL3 is clearly present in human male amniotic fluid in the second trimester, where abdominal testis translocation takes place.
18433302 study suggests for the first time a role for INSL3/RXFP2 signaling in bone metabolism and links RXFP2 gene mutations with human osteoporosis
18310050 INSL3 concentration in human amniotic fluid is potentially predictive of fetal sex and pre-eclampsia, and presumably reflects the functioning of the fetal Leydig cell population.
18063691 negative cooperativity is present and that INSL3-RXFP2 binding shows both similarities and differences with insulin binding to the insulin receptor
17666478 In boys, early postnatal INSL3 is markedly higher as compared with later childhood, presumably because it is stimulated by the transient postnatal LH peak
17559848 The common INSL3 G178A polymorphism was not statistically significantly associated with male infertility.
17549672 Higher blood levels may be indicative of ovarian cancer.
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 Observational study of gene-disease association. (HuGE Navigator)
17437853 Mutations involving the insulin-like factor 3 gene may contribute to other anomalies of male genital development, such as micropenis.
17356050 INSL3 could be considered a new circulating hormone related to LH-dependent ovarian hyperandrogenism, particularly in normal-weight polycystic ovary women
17314233 INSL3 blood levels may be higher in men with persistent spermatogenesis during treatment with male hormonal contraceptives.
17028442 Observational study of gene-disease association. (HuGE Navigator)
17028442 The results, in conjunction with the previous data, suggest that mutations of INSL3 and LGR8/GREAT remain rare, and that the Thr/Thr genotype of Ala60Thr polymorphism in INSL3 may constitute a susceptibility factor for the development of cryptorchidism.
17014531 The data show that INSL3 is an independent measure of Leydig cell function (quality and number), which appears to be independent of acute control via the HPG axis.
16867980 INSL3 was found to adopt a characteristic relaxin/insulin-like fold in solution but is a highly dynamic molecule. The four termini of this two-chain peptide are disordered, and additional conformational exchange is evident in the molecular core.
16687567 Observational study of gene-disease association. (HuGE Navigator)
16687567 Results showed a significant association of INSL3 gene mutations in men presenting one or more signs of testicular dysgenesis syndrome.
16467267 Thus, the human INSL3 promoter constitutes a novel target for the orphan nuclear receptor Nur77.
16394084 INSL3 is not sensitive to gonadotropin stimulation in normal men, but declines markedly in response to gonadotropin deprivation.
16010410 Strongest INSL3 expression was detected in the basal epithelial cell compartment of the prostate epithelial cells, while weaker mRNA expression and immunoreactive production were observed in secretory epithelial cells.
15956751 Analysis of men treated with different combinations of hormones of the hypothalamus-pituitary-testis axis suggests that the production of INSL3 is related to the luteinizing hormone
15956746 relaxin-like hormones appear to be present early during C-cell hyperplasia and potentially functional relaxin/INSL3 ligand-receptor systems are present in human medullary thyroid carcinoma tissues and cell lines
15755855 Even testosterone and INSL3 are both dependent on lutropin, thesse two Leydig cell hormones are regulated differently.
15708846 LGR8 signal is activated by the relaxin-like factor
15579790 Although a common polymorphism was identified in the INSL3 gene, no mutations were observed. Lack of association between genetic factors necessary for correct testicular descent and anorchia.
15579743 Analysis of men treated with different combinations of hormones of the hypothalamus-pituitary-testis axis suggests that the production of INSL3 is related to LH in a manner similar to that of the LH-testosterone axis.
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
12684664 differentially expressed in hyperplastic and neoplastic thyrocytes, and in various thyroid diseases
12601553 A novel mutation in this protein is found in patients with cryptorchidism.
11383919 Observational study of gene-disease association. (HuGE Navigator)
11182749 Observational study of gene-disease association. (HuGE Navigator)
11095425 Observational study of gene-disease association. (HuGE Navigator)
10391220 Functional analysis of the mouse counterpart.

AA Sequence


Text Mined References (100)

PMID Year Title
26625974 2016 Polymorphisms and haplotypes of insulin-like factor 3 gene are associated with risk of polycystic ovary syndrome in Indian women.
26579638 2015 Anti-müllerian hormone and insulin-like 3 levels in healthy normal-weight ovulatory and anovulatory eumenorrheic late adolescent females: potential early biomarkers of ovarian dysfunction?
26077926 2016 INSL3 stimulates spermatogonial differentiation in testis of adult zebrafish (Danio rerio).
25728210 2014 Genetic analysis of the human Insulin-like 3 gene: absence of mutations in a Greek paediatric cohort with testicular maldescent.
25516081 2015 Longitudinal assessment of circulating insulin-like peptide 3 levels in healthy peripubertal girls.
24908673 2014 Expression patterns of DLK1 and INSL3 identify stages of Leydig cell differentiation during normal development and in testicular pathologies, including testicular cancer and Klinefelter syndrome.
24659579 2014 Low INSL3 in Klinefelter syndrome is related to osteocalcin, testosterone treatment and body composition, as well as measures of the hypothalamic-pituitary-gonadal axis.
24640568 2013 Plasma insulin-like factor 3 (INSL3) in male patients with osteoporosis and Klinefelter's syndrome.
24243640 2014 Insulin-like peptide 3 (INSL3) in men with congenital hypogonadotropic hypogonadism/Kallmann syndrome and effects of different modalities of hormonal treatment: a single-center study of 281 patients.
23928669 2013 Parallel variations of insulin-like peptide 3 (INSL3) and antimüllerian hormone (AMH) in women with the polycystic ovary syndrome according to menstrual cycle pattern.
23539510 2013 Insulin-like factor 3 promotes wound healing at the ocular surface.
23150680 2013 Normal insulin-like peptide-3 levels despite low testosterone in adult males with Prader-Willi syndrome: variations in Leydig cell function from infancy through adulthood.
23028900 2012 Innate immunity and non-Hodgkin's lymphoma (NHL) related genes in a nested case-control study for gastric cancer risk.
22574850 2012 Replacement of disulfides by amide bonds in the relaxin-like factor (RLF/INSL3) reveals a role for the A11-B10 link in transmembrane signaling.
22216350 2011 Profiling insulin like factor 3 (INSL3) signaling in human osteoblasts.
21586896 2011 Basal insulin-like factor 3 levels predict functional ovarian hyperandrogenism in the polycystic ovary syndrome.
20713036 2010 The effect of obesity on testicular function by insulin-like factor 3, inhibin B, and leptin concentrations in obese adolescents according to pubertal stages.
20570702 2010 Role of the intra-A-chain disulfide bond of insulin-like peptide 3 in binding and activation of its receptor, RXFP2.
20560146 2011 Design and development of analogues of dimers of insulin-like peptide 3 B-chain as high-affinity antagonists of the RXFP2 receptor.
20550598 2011 Human testicular insulin-like factor 3: in relation to development, reproductive hormones and andrological disorders.
20438785 2010 Polymorphisms in innate immunity genes and risk of childhood leukemia.
20406964 2010 Risk of meningioma and common variation in genes related to innate immunity.
20200332 2010 Family-based analysis of candidate genes for polycystic ovary syndrome.
20082125 2010 In vitro degradation of insulin-like peptide 3 by insulin-degrading enzyme.
19950223 2010 INSL3 has tumor-promoting activity in thyroid cancer.
19773279 2009 Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity.
19755411 2009 Peripheral insulin-like factor 3 concentrations are reduced in men with type 2 diabetes mellitus: effect of glycemic control and visceral adiposity on Leydig cell function.
19423540 2009 Common variation in genes related to innate immunity and risk of adult glioma.
19416220 2009 Lysosomal acid hydrolases of the cathepsin family are novel targets of INSL3 in human thyroid carcinoma cells.
19416190 2009 Mutations in INSL3 and RXFP2 genes in cryptorchid boys.
19416188 2009 INSL3/RXFP2 signaling in testicular descent.
19416166 2009 The "hot wires" of the relaxin-like factor (Insl3).
19329805 Biology of insulin-like factor 3 in human reproduction.
19226271 2009 Insulin-like factor 3 as a marker of testicular function in obese men.
19110449 The novel hormone INSL3 is expressed in human testicular Leydig cell tumors: a clinical and immunohistochemical study.
19086273 2008 Solution structure of a conformationally restricted fully active derivative of the human relaxin-like factor.
19067106 2010 Effect of helix-promoting strategies on the biological activity of novel analogues of the B-chain of INSL3.
19017913 2008 Genetic alterations associated with cryptorchidism.
18772597 2008 No association between T222P/LGR8 mutation and cryptorchidism in the Moroccan population.
18611973 2008 Insulin-like factor 3 levels in second-trimester amniotic fluid.
18433302 2008 Mutations in the insulin-like factor 3 receptor are associated with osteoporosis.
18310050 2008 Insulin-like factor 3 levels in amniotic fluid of human male fetuses.
18063691 2008 Cooperative binding of insulin-like Peptide 3 to a dimeric relaxin family peptide receptor 2.
17666478 2007 Insulin-like factor 3 levels in cord blood and serum from children: effects of age, postnatal hypothalamic-pituitary-gonadal axis activation, and cryptorchidism.
17559848 2007 Preliminary analysis of the G178A polymorphism of insulin-like factor 3 in male infertility.
17549672 Elevated plasma levels of the novel hormone INSL3 in a woman with metastatic ovarian cancer.
17473281 2007 Defining the LGR8 residues involved in binding insulin-like peptide 3.
17437853 2007 Novel mutations involving the INSL3 gene associated with cryptorchidism.
17356050 2007 Insulin-like factor 3: a new circulating hormone related to luteinizing hormone-dependent ovarian hyperandrogenism in the polycystic ovary syndrome.
17314233 Elevated end-of-treatment serum INSL3 is associated with failure to completely suppress spermatogenesis in men receiving male hormonal contraception.
17028442 2007 Mutation and polymorphism analyses of INSL3 and LGR8/GREAT in 62 Japanese patients with cryptorchidism.
17014531 2006 Peripheral INSL3 concentrations decline with age in a large population of Australian men.
16867980 2006 Solution structure and characterization of the LGR8 receptor binding surface of insulin-like peptide 3.
16687567 2006 Insulin-like factor 3 gene mutations in testicular dysgenesis syndrome: clinical and functional characterization.
16467267 2005 Role of nuclear receptors in INSL3 gene transcription in Leydig cells.
16394084 2006 The effects of gonadotropin suppression and selective replacement on insulin-like factor 3 secretion in normal adult men.
16010410 2005 INSL3 in the benign hyperplastic and neoplastic human prostate gland.
15956751 2005 Insulin-like factor 3: a novel circulating hormone of testicular origin in humans.
15956746 2005 Human medullary thyroid carcinoma: a source and potential target for relaxin-like hormones.
15755855 2005 Insulin-like factor 3 serum levels in 135 normal men and 85 men with testicular disorders: relationship to the luteinizing hormone-testosterone axis.
15708846 2005 LGR8 signal activation by the relaxin-like factor.
15592455 2005 Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.
15579790 2004 An analysis of the genetic factors involved in testicular descent in a cohort of 14 male patients with anorchia.
15579743 2004 A novel circulating hormone of testis origin in humans.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15340161 2004 Signal peptide prediction based on analysis of experimentally verified cleavage sites.
15057824 2004 The DNA sequence and biology of human chromosome 19.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14615376 2004 Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation.
12970298 2003 The INSL3-LGR8/GREAT ligand-receptor pair in human cryptorchidism.
12684664 2003 INSL-3 is expressed in human hyperplastic and neoplastic thyrocytes.
12601553 2003 A novel mutation of the insulin-like 3 gene in patients with 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.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12200137 2002 IL-2 receptor signaling through the Shb adapter protein in T and NK cells.
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.
11746019 2001 Novel insulin-like 3 (INSL3) gene mutation associated with human cryptorchidism.
11383919 2001 Different insulin-like 3 (INSL3) gene mutations not associated with human cryptorchidism.
11380919 2001 Ala/Thr60 variant of the Leydig insulin-like hormone is not associated with cryptorchidism in the Japanese population.
11182749 2001 Genetic analysis of the INSL3 gene in patients with maldescent of the testis.
11147585 2000 Relaxin-like factor (RLF) is differentially expressed in the normal and neoplastic human mammary gland.
11095425 2000 Insulin-like 3/relaxin-like factor gene mutations are associated with cryptorchidism.
10982185 2000 Complete genomic organization of the human JAK3 gene and mutation analysis in severe combined immunodeficiency by single-strand conformation polymorphism.
10899310 2000 STAM2, a new member of the STAM family, binding to the Janus kinases.
10759163 2000 A common polymorphism in the human relaxin-like factor (RLF) gene: no relationship with cryptorchidism.
10729310 2000 Absence of mutations involving the INSL3 gene in human idiopathic cryptorchidism.
10451226 1999 The relaxin-like factor is a hormone.
10391220 1999 Cryptorchidism in mice mutant for Insl3.
9753072 1998 Molecular and biochemical characterization of JAK3 deficiency in a patient with severe combined immunodeficiency over 20 years after bone marrow transplantation: implications for treatment.
9354668 1997 Structural and functional basis for JAK3-deficient severe combined immunodeficiency.
8662778 1996 Expression of Janus kinase 3 in human endothelial and other non-lymphoid and non-myeloid cells.
8253799 1993 Cloning of a cDNA for a novel insulin-like peptide of the testicular Leydig cells.
8034302 1994 A human cDNA coding for the Leydig insulin-like peptide (Ley I-L).
8022790 1994 Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes.
8022486 1994 Involvement of the Jak-3 Janus kinase in signalling by interleukins 2 and 4 in lymphoid and myeloid cells.
8020942 1994 Structural organization of the porcine and human genes coding for a Leydig cell-specific insulin-like peptide (LEY I-L) and chromosomal localization of the human gene (INSL3).
7852540 1995 The human Leydig insulin-like (hLEY I-L) gene is expressed in the corpus luteum and trophoblast.
7659163 1995 Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID).
7559633 1995 A kinase-deficient splice variant of the human JAK3 is expressed in hematopoietic and epithelial cancer cells.