RET, ret proto-oncogene, 5979

N. diseases: 607; N. variants: 162
Disease: Hirschsprung Disease ×
Source: ALL
Disease Score gda Association Type Type Original DB Sentence supporting the association PMID PMID Year
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 GeneticVariation disease BEFREE In addition, case-control analysis demonstrated that RET rs2435357 is significantly correlated with HSCR (P = 2.2 × 10(-13)) with an odds ratio of 5.1 (95% confidence interval = 3.2-8.1). 27338539 2016
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 GeneticVariation disease BEFREE In humans, RET activating mutations cause multiple endocrine neoplasia, whereas inactivating mutations are responsible for Hirschsprung disease. 21490379 2011
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 GeneticVariation disease BEFREE The unknown functional disease variant(s), with a dosage-dependent effect in HSCR, is likely to be located in the 5'-region of the RET gene. 18612588 2008
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 GeneticVariation disease BEFREE We now show that a common non-coding RET variant within a conserved enhancer-like sequence in intron 1 is significantly associated with HSCR susceptibility and makes a 20-fold greater contribution to risk than rare alleles do. 15829955 2005
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 GeneticVariation disease BEFREE Inactivating mutations in RET cause the Hirschsprung's disease characterized by megacolon aganglionosis. 17934909 2007
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 GeneticVariation disease BEFREE Inactivating mutations of the RET proto-oncogene and of one of its soluble ligand molecules, glial cell line derived neurotrophic factor (GDNF), have been found in a subset of patients with Hirschsprung disease (HSCR). 10204848 1999
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 Biomarker disease BEFREE Both null and missense mutations impaired the interaction of TCF4 with ASCL1 from the PHOX-RET pathway in transactivating an E box-containing reporter construct; therefore, hyperventilation and Hirschsprung disease in patients with Pitt-Hopkins syndrome might be explained by altered development of noradrenergic derivatives. 17436255 2007
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 Biomarker disease BEFREE The full application of the proposed protocol in most of the unexplained HSCR cases will allow us to establish the precise role of RET not only in causing but also in predisposing to HSCR pathogenesis. 12865274 2003
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 GeneticVariation disease BEFREE Taken together, the low penetrance of the mutant gene, the lack of genotype-phenotype correlation, the sex-dependent effect of RET mutations and the variable clinical expression of the disease support the existence of one or more modifier genes in familial HSCR. 7581377 1995
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 Biomarker disease BEFREE Although RET is a well-established risk factor, a recent genome-wide association study (GWAS) of HSCR has identified NRG1 as an additional susceptibility locus. 25310821 2014
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 AlteredExpression disease BEFREE Germline and somatic mutations in RET that produce constitutively activated receptors cause the cancer syndrome multiple endocrine neoplasia type 2 and several endocrine and neural-crest-derived tumors, whereas mutations resulting in nonfunctional RET or lower expression of RET are found in individuals affected with Hirschsprung disease. 16979782 2006
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 GeneticVariation disease BEFREE Germline RET mutations in Hirschsprung disease are mainly inactivating, and have been reported to account for up to 20 and 50% of sporadic and familial cases, respectively. 9727738 1998
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 GeneticVariation disease BEFREE Such a functional effect of this common RET variant explains the under-representation of the whole haplotype and its role as a modifying factor in HSCR pathogenesis. 16986122 2007
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 GeneticVariation disease BEFREE MEN2A and MEN2B have recently been mapped within the centromeric region closely linked to RBP3 and D10S15 (which are located inside the deletion) and cosegregate with HSCR in at least two different pedigrees. 8467706 1993
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 GeneticVariation disease BEFREE The germline mutation was detected because of the systematic genetic screening of the RET proto-oncogene, which is useful for genetic counseling of potential risk of HSCR and MTC in other family members. 15991157 2005
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 GeneticVariation disease BEFREE Of interest, strong linkage disequilibrium (LD) between RET S836S and 3'UTR variants has been reported in Hirschsprung's disease patients. 26829565 2016
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 Biomarker disease BEFREE RET is a candidate gene for IHPS due to its role in the development of the intrinsic innervation and ganglia of the smooth musculature and the association of RET variants with another motility disorder (Hirschsprung's disease). 22169991 2011
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 GeneticVariation disease BEFREE This distinctive feature of RET mutations associated with Hirschsprung's disease and of the RET mutations associated with thyroid cancer indicates a basic biological difference between the mutational events leading to the different phenotypes. 9043870 1996
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 GeneticVariation disease BEFREE In addition, there was strong evidence against linkage to two Hirschsprung disease susceptibility genes (RET and EDNRB), a condition that can cosegregate with neuroblastoma as in one of the kindreds tested here. 9516825 1997
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 GeneticVariation disease BEFREE Our study investigates the correlation between mutations in the RET locus and symptom severity in HSCR. 23114404 2013
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 GeneticVariation disease BEFREE Of note, the novel R645C mutation was detected in 2 affected siblings of a HSCR family also carrying a RET splicing mutation. 19040714 2009
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 Biomarker disease CTD_human Using flanking intronic sequences as primers to amplify 12 of the 20 exons of RET from genomic DNA of 27 Hirschsprung's disease patients, we have now identified four mutations (one frameshift and three missense) that totally disrupt or partially change the structure of the tyrosine kinase domain of the RET protein (Ret). 8114938 1994
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 Biomarker disease LHGDN Diminished Ret expression compromises neuronal survival in the colon and causes intestinal aganglionosis in mice. 18414682 2008
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 CausalMutation disease CLINVAR Comprehensive Genomic Profiling of Clinically Advanced Medullary Thyroid Carcinoma. 27207748 2016
CUI: C0019569
Disease: Hirschsprung Disease
Hirschsprung Disease 		0.700 GeneticVariation disease BEFREE Although the picture is complex, recent associations between specific RET proto-oncogene variations have been shown to be significant in Down syndrome patients with Hirschsprung disease, as they probably interfere with vital RET functions in the development of the autonomic and enteric nervous systems, increasing the risk of disturbed normal function. 30218169 2018