SIX3, SIX homeobox 3, 6496

N. diseases: 117; N. variants: 14
Source: ALL
Disease Score gda Association Type Type Original DB Sentence supporting the association PMID PMID Year
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 GeneticVariation disease BEFREE Our findings show that variations in Six3 dosage result in different forms of HPE. 27770010 2016
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 Biomarker disease BEFREE Our data indicate that SIX3 is a frequent target in the pathogenesis of HPE and demonstrate how this can inform the genetic counseling of families. 18791198 2008
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 GeneticVariation disease BEFREE We studied two genes, Sonic Hedgehog (SHH) and SIX3, in which mutations have been reported in patients showing SMMCI as part of the HPE spectrum. 11471164 2001
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 Biomarker disease BEFREE These results demonstrate physical and functional association between EYA4 and SIX3, suggesting that EYA4 is a novel candidate gene of HPE, whose haploinsufficiency leads to HPE through the compromised function of SIX3. 19606496 2009
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 GeneticVariation disease BEFREE Frank holoprosencephaly was present in 11 individuals with deletions of one of the common HPE genes SHH, ZIC2, SIX3, and TGIF1, in one individual with a deletion of the HPE8 locus at 14q13, and in one individual with a deletion of FGF8, whereas deletions of other HPE loci and candidate genes (FOXA2 and LRP2) expressed microforms of HPE. 20066439 2010
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 Biomarker disease BEFREE In humans, SIX3 haploinsufficiency results in holoprosencephaly, a defect in anterior midline formation. 28093895 2017
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 GeneticVariation disease BEFREE These functions are very likely conserved among bilaterians since vertebrate six3 is required for neuroendocrine and median brain development with certain mutations leading to holoprosencephaly. 22216011 2011
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 GeneticVariation disease BEFREE Holoprosencephaly (HPE) is genetically heterogeneous with four genes, SIX3, SHH, TGIF, and ZIC2 that have been identified to date and that are altered in 12% of patients. 11479728 2001
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 Biomarker disease BEFREE This usually includes analysis of chromosomes by high-resolution karyotyping, clinical assessment to rule-out well recognized syndromes that are associated with HPE (e.g., Pallister-Hall syndrome, Smith-Lemli-Opitz syndrome and others), and molecular studies of the most common HPE associated genes (e.g., SHH, ZIC2 and SIX3). 20104604 2010
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 Biomarker disease BEFREE These data suggest a direct link between Six3 and Shh regulation during normal forebrain development and in the pathogenesis of HPE. 18836447 2008
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 Biomarker disease BEFREE To identify whether any mutations of candidate genes including SHH, ZIC2, SIX3, and TGIF exist in a Taiwanese family segregated with holoprosencephaly (HPE) and moyamoya disease. 16475235 2006
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 Biomarker disease BEFREE These YACs narrow the HPE2 critical region to less than 1 Mb and are now being further analyzed to identify the gene causing holoprosencephaly on chromosome 2. 8824878 1996
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 GeneticVariation disease BEFREE A novel SIX3 mutation segregates with holoprosencephaly in a large family. 19353631 2009
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 GeneticVariation disease BEFREE Our cases suggest that SIX3 mutations result in a more severe phenotype than other gene mutations for holoprosencephaly. 17001667 2006
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 GeneticVariation disease BEFREE SHH mutations more commonly resulted in non-HPE (64%) than frank HPE (36%), and non-HPE was significantly more common in patients with SHH than in those with mutations in the other common HPE related genes (p<0.0001 compared to ZIC2 or SIX3). 22791840 2012
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 Biomarker disease BEFREE Using samples from a population-based birth defects registry in California, we performed a mutational analysis of the known HPE genes Sonic Hedgehog (SHH), ZIC2, and SIX3, in addition to two HPE candidate genes, TG-interacting factor (TGIF), and Patched (PTC), on a group of sporadic HPE patients. 10710230 2000
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 GeneticVariation disease BEFREE The most severe HPE types were associated with SIX3 and ZIC2 mutations, whereas microforms were associated with SHH mutations. 21940735 2011
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 GeneticVariation disease BEFREE Mutational analysis has identified four different mutations in the homeodomain of SIX3 that are predicted to interfere with transcriptional activation and are associated with HPE. 10369266 1999
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 GeneticVariation disease BEFREE We therefore considered holoprosencephaly (HPE)-associated genes as potential SCH candidates and report for the first time heterozygous mutations in SIX3 and SHH in a total of three unrelated patients and one fetus with SCH; one of them without obvious associated malformations of midline forebrain structures. 20157829 2010
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 GeneticVariation disease BEFREE Functional characterization of SIX3 homeodomain mutations in holoprosencephaly: interaction with the nuclear receptor NR4A3/NOR1. 15523651 2004
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 GeneticVariation disease BEFREE A new mutation in the six-domain of SIX3 gene causes holoprosencephaly. 11039582 2000
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 Biomarker disease BEFREE We report 22 patients with normal neuropsychological development and a holoprosencephaly-like (HPE-like) phenotype screened for SHH, SIX3, TGIF, and GLI2. 17001669 2006
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 Biomarker disease BEFREE Sequencing of the CDON, SHH, ZIC2, SIX3, and TGIF genes (associated with holoprosencephaly) did not disclose pathogenic alterations. 21995818 2012
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 GeneticVariation disease BEFREE A missense mutation c.686C>T was found in the gene SIX3 of one patient, which did not differ from the accepted 20% of known HPE gene mutations among all HPE cases. 17584896 2007
CUI: C0079541
Disease: Holoprosencephaly
Holoprosencephaly
0.700 Biomarker disease BEFREE Two families showed inherited deletions that contain SIX3 and were incompletely penetrant for HPE. 28670735 2018