CAKUT

Gene: SIX5

Red List (low evidence)

SIX5 (SIX homeobox 5)
EnsemblGeneIds (GRCh38): ENSG00000177045
EnsemblGeneIds (GRCh37): ENSG00000177045
OMIM: 600963, Gene2Phenotype
SIX5 is in 11 panels

4 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 Green to Red.
Created: 22 Oct 2025, 1:26 p.m. | Last Modified: 22 Oct 2025, 1:26 p.m.
Panel Version: 1.179

Helen Stuart (University of Manchester)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Bill Newman (Manchester Centre for Genomic Medicine)

Green List (high evidence)

Ellen McDonagh (Genomics England Curator)

Comment on list classification: Promoted from amber to green as two reviewers in agreement.
Created: 29 Mar 2016, 10:36 a.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Branchiootorenal syndrome 2, OMIM:610896
OMIM
600963
Clinvar variants
Variants in SIX5
Penetrance
Complete
Panels with this gene

History Filter Activity

22 Oct 2025, Gel status: 1

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

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

22 Oct 2025, Gel status: 1

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

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

29 Mar 2016, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for SIX5 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

29 Mar 2016, Gel status: 4

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

29 Mar 2016, Gel status: 4

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

14 Jul 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

SIX5 was added to Congenital Anomaly of the Kidneys and Urinary Tract (CAKUT)panel. Sources: UKGTN,Radboud University Medical Center, Nijmegen

14 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

SIX5 was added to Congenital Anomaly of the Kidneys and Urinary Tract (CAKUT)panel. Sources: UKGTN,Radboud University Medical Center, Nijmegen