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Deafness_IsolatedAndComplex

Gene: SIX5

Red List (low evidence)

SIX5 (SIX homeobox 5)
EnsemblGeneIds (GRCh38): ENSG00000177045
EnsemblGeneIds (GRCh37): ENSG00000177045
OMIM: 600963, Gene2Phenotype
SIX5 is in 7 panels

1 review

Lilian Downie (Victorian Clinical Genetics Services)

Red List (low evidence)

ClinGEn expert review:
The SIX5 gene has been associated with autosomal dominant branchio-oto-renal syndrome using the ClinGen Clinical Validity Framework as of 4/20/2017. This association was made using case-level data only. At least 5 missense variants have been reported in humans. SIX5 was first associated with this disease in humans as early as 2007 (Hoskins et al.). Association has been reported in at least 6 probands in 2 publications (17357085, 24429398), however the reported variants are high in frequency in population databases, have no evidence of pathogenicity, and/or an alternate cause of disease has later been reported (21280147). This gene-disease association is supported by protein interaction and biochemical function studies (14704431, 17357085, 11950062). While EYA1 and SIX1 gene inactivation in mice leads to ear and kidney abnormalities, two independent SIX5 mouse models have cataracts and no ear or kidney abnormalities (10802667, 10802668). In summary, there is convincing evidence disputing the association between SIX5 and autosomal dominant branchio-oto-renal syndrome. More evidence is needed to either support or refute the role SIX5 plays in this disease.
Created: 28 Jan 2020, 11:07 p.m. | Last Modified: 28 Jan 2020, 11:07 p.m.
Panel Version: 0.254

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
branchio-oto-renal syndrome

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Melbourne Genomics Health Alliance Deafness Flagship
  • Victorian Clinical Genetics Services
Phenotypes
  • Branchiootorenal syndrome 2, MIM#610896
Tags
disputed
OMIM
600963
Clinvar variants
Variants in SIX5
Penetrance
None
Publications
Panels with this gene

History Filter Activity

1 Jan 2022, Gel status: 1

Added Tag

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Tag disputed tag was added to gene: SIX5.

29 Jan 2020, Gel status: 1

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: six5 has been classified as Red List (Low Evidence).

29 Jan 2020, Gel status: 1

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: SIX5 were set to

29 Jan 2020, Gel status: 1

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: SIX5 were changed from to Branchiootorenal syndrome 2, MIM#610896

29 Jan 2020, Gel status: 1

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: SIX5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

29 Jan 2020, Gel status: 1

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: six5 has been classified as Red List (Low Evidence).

17 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: SIX5 was added gene: SIX5 was added to Deafness_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Deafness Flagship Mode of inheritance for gene: SIX5 was set to Unknown