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: C0266667
Disease: Cyclocephaly
Cyclocephaly 		0.110 GeneticVariation disease BEFREE We report a new HPE family, presenting a wide spectrum of clinical features, ranging from cyclopia to hypotelorism, in which a mutation was found for the first time in the SIX domain of SIX3: a GG insertion creates a frameshift leading to a nonsense mutation downstream in the homeodomain region. 11039582 2000
CUI: C1840235
Disease: SOLITARY MEDIAN MAXILLARY CENTRAL INCISOR
SOLITARY MEDIAN MAXILLARY CENTRAL INCISOR 		0.110 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: C0021704
Disease: Intelligence
Intelligence 		0.100 GeneticVariation phenotype GWASCAT Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence. 29942086 2018
CUI: C0021704
Disease: Intelligence
Intelligence 		0.100 GeneticVariation phenotype GWASCAT Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. 29844566 2018
CUI: C0027627
Disease: Neoplasm Metastasis
Neoplasm Metastasis 		0.030 GeneticVariation phenotype BEFREE Restoration of SIX3 in lung cancer cells lacking endogenous SIX3 suppressed cell proliferation and migration, and downregulated a number of genes involved in proliferation and metastasis such as S100P, TGFB3, GINS3 and BAG1. 23977152 2013
CUI: C0000768
Disease: Congenital Abnormality
Congenital Abnormality 		0.020 GeneticVariation group 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: C0685869
Disease: Monophthalmos
Monophthalmos 		0.010 GeneticVariation disease BEFREE We report a new HPE family, presenting a wide spectrum of clinical features, ranging from cyclopia to hypotelorism, in which a mutation was found for the first time in the SIX domain of SIX3: a GG insertion creates a frameshift leading to a nonsense mutation downstream in the homeodomain region. 11039582 2000
CUI: C1304508
Disease: Spindle cell hemangioma
Spindle cell hemangioma 		0.010 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: C1834877
Disease: HOLOPROSENCEPHALY 2 (disorder)
HOLOPROSENCEPHALY 2 (disorder) 		0.920 Biomarker disease BEFREE Large heterozygous deletions associated with human holoprosencephaly type 2 have been previously mapped to 2p21, opening the possibility that SIX3 could be involved in the development of midline structures of the head. 10415461 1999
CUI: C1834877
Disease: HOLOPROSENCEPHALY 2 (disorder)
HOLOPROSENCEPHALY 2 (disorder) 		0.920 Biomarker disease GENOMICS_ENGLAND Mutations in the human SIX3 gene in holoprosencephaly are loss of function. 18791198 2008
CUI: C1834877
Disease: HOLOPROSENCEPHALY 2 (disorder)
HOLOPROSENCEPHALY 2 (disorder) 		0.920 Biomarker disease MGD Haploinsufficiency of Six3 fails to activate Sonic hedgehog expression in the ventral forebrain and causes holoprosencephaly. 18694563 2008
CUI: C1834877
Disease: HOLOPROSENCEPHALY 2 (disorder)
HOLOPROSENCEPHALY 2 (disorder) 		0.920 Biomarker disease MGD Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development. 12569128 2003
CUI: C1834877
Disease: HOLOPROSENCEPHALY 2 (disorder)
HOLOPROSENCEPHALY 2 (disorder) 		0.920 Biomarker disease GENOMICS_ENGLAND A broad range of ophthalmologic anomalies is part of the holoprosencephaly spectrum. 21976454 2011
CUI: C1834877
Disease: HOLOPROSENCEPHALY 2 (disorder)
HOLOPROSENCEPHALY 2 (disorder) 		0.920 Biomarker disease GENOMICS_ENGLAND Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly. 10369266 1999
CUI: C1834877
Disease: HOLOPROSENCEPHALY 2 (disorder)
HOLOPROSENCEPHALY 2 (disorder) 		0.920 Biomarker disease CTD_human
CUI: C1834877
Disease: HOLOPROSENCEPHALY 2 (disorder)
HOLOPROSENCEPHALY 2 (disorder) 		0.920 Biomarker disease GENOMICS_ENGLAND
CUI: C1834877
Disease: HOLOPROSENCEPHALY 2 (disorder)
HOLOPROSENCEPHALY 2 (disorder) 		0.920 Biomarker disease GENOMICS_ENGLAND
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 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 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 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 Biomarker disease CTD_human 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