Deafness and congenital structural abnormalities
Gene: SIX5EnsemblGeneIds (GRCh38): ENSG00000177045
EnsemblGeneIds (GRCh37): ENSG00000177045
OMIM: 600963, Gene2Phenotype
SIX5 is in 11 panels
7 reviews
Arina Puzriakova (Genomics England Curator)
Comment on list classification: This gene-disease association has been rated as 'DISPUTED' by ClinGen (https://search.clinicalgenome.org/CCID:006145) Multiple families reported but 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). Two independent SIX5 mouse models have cataracts and no ear or kidney abnormalities (10802667, 10802668) which are typical of branchio-oto-renal syndrome.
As the evidence for the association of SIX5 with branchio-oto-renal syndrome is disputed, downgraded this gene from Amber to Red.Created: 22 Oct 2025, 1:28 p.m. | Last Modified: 22 Oct 2025, 1:28 p.m.
Panel Version: 1.36
Muriel Holder (Clinical Genetics, Guy's Hospital)
BOR phenotypeCreated: 17 Oct 2016, 12:32 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of pathogenicity
Other
Sarah Leigh (Genomics England Curator)
Comment when marking as ready: Three separate autosomal dominant variants reported in three patients with Branchiootorenal syndrome 2 610896, only two of whom had ear anomoliesCreated: 5 Oct 2016, 8:26 a.m.
Associated with phenotype in OMIM and as a confirmed Developmental Disorder Gene / G2P. Three variants reported.Created: 20 Sep 2016, 7:10 a.m.
Comment on mode of inheritance: MOI from DecipherCreated: 20 Sep 2016, 7:10 a.m.
Ellen McDonagh (Genomics England Curator)
Comment on list classification: Red gene on the Bilateral microtia (Version 1.10), Ear malformations with hearing impairment (Version 0.103) and Familial hemifacial microsomia (Version 0.148) gene panels which were combined to create this panel. However it is rated green and diagnostic by one reviewer, therefore unsure whether this should be green due to the phenotype.Created: 14 Oct 2016, 1:39 p.m.
Ana Beleza (Bristol Regional Genetics Service)
Variants in this GENE are reported as part of current diagnostic practice
Maria Bitner-Glindzicz (UCL)
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
- Sources
-
- Expert Review Red
- UKGTN
- Emory Genetics Laboratory
- Radboud University Medical Center, Nijmegen
- Expert list
- Phenotypes
-
- Branchiootorenal syndrome 2, OMIM:610896
- OMIM
- 600963
- Clinvar variants
- Variants in SIX5
- Penetrance
- Complete
- Publications
- Panels with this gene
-
- Unexplained young onset end-stage renal disease - additional genes
- Deafness and congenital structural abnormalities
- Unexplained kidney failure in young people
- Ductal plate malformation
- DDG2P
- Monogenic hearing loss
- Fetal anomalies
- Clefting
- Bilateral congenital or childhood onset cataracts
- Intellectual disability
- CAKUT
History Filter Activity
Entity classified by Genomics England curator
Arina Puzriakova (Genomics England Curator)Gene: six5 has been classified as Red List (Low Evidence).
Set Phenotypes
Arina Puzriakova (Genomics England Curator)Phenotypes for gene: SIX5 were changed from Bilateral Microtia; Branchiootorenal syndrome 2 to Branchiootorenal syndrome 2, OMIM:610896
panel promoted to version 1
Ellen McDonagh (Genomics England Curator)26th Oct 2016: the panels Bilateral microtia version 1.10, Ear malformations with hearing impairment version 0.105, and familial hemifacial microsomia version 0.149 gene panels were combined to create this panel. The panel was revised due to expert review, further curation of evidence and internal clinical evaluation. Ready for promotion to version 1.
Set publications
Ellen McDonagh (Genomics England Curator)Publications for SIX5 were set to 10773454; 10802667; 10802668; 11978764; 14704431; 15163633; 17357085; 21280147; 7777532; 8595416; 9158137; 9241282; 9241283; 9949207
Gene classified by Genomics England curator
Ellen McDonagh (Genomics England Curator)This gene has been classified as Amber List (Moderate Evidence).
Set Mode of Inheritance, Added New Source
Sarah Leigh (Genomics England Curator)SIX5 was added to Deafness and congenital structural abnormalitiespanel. Source: Emory Genetics Laboratory SIX5 was added to Deafness and congenital structural abnormalitiespanel. Source: Radboud University Medical Center, Nijmegen SIX5 was added to Deafness and congenital structural abnormalitiespanel. Source: UKGTN Model of inheritance for gene SIX5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added New Source
Sarah Leigh (Genomics England Curator)SIX5 was added to Deafness and congenital structural abnormalitiespanel. Sources: Expert list,Expert Review Red
Created
Sarah Leigh (Genomics England Curator)SIX5 was created by sleigh