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: 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 GeneticVariation disease UNIPROT 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 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 GeneticVariation disease UNIPROT The unfolding clinical spectrum of holoprosencephaly due to mutations in SHH, ZIC2, SIX3 and TGIF genes. 20531442 2010
CUI: C1834877
Disease: HOLOPROSENCEPHALY 2 (disorder)
HOLOPROSENCEPHALY 2 (disorder) 		0.920 GeneticVariation disease UNIPROT Functional characterization of SIX3 homeodomain mutations in holoprosencephaly: interaction with the nuclear receptor NR4A3/NOR1. 15523651 2004
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 GeneticVariation disease UNIPROT Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: Mutation review and genotype-phenotype correlations. 15221788 2004
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 GeneticVariation disease UNIPROT 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 GENOMICS_ENGLAND
CUI: C1834877
Disease: HOLOPROSENCEPHALY 2 (disorder)
HOLOPROSENCEPHALY 2 (disorder) 		0.920 GeneticVariation disease UNIPROT SIX3 mutations with holoprosencephaly. 17001667 2006
CUI: C1834877
Disease: HOLOPROSENCEPHALY 2 (disorder)
HOLOPROSENCEPHALY 2 (disorder) 		0.920 AlteredExpression disease BEFREE However, embryonic SIX3 expression is not limited to the eye field, and SIX3 has been found to be mutated in some patients with holoprosencephaly type 2 (HPE2), suggesting that SIX3 has wide implications in head development. 10512683 1999
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 CausalMutation disease CLINVAR
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