Pituitary hormone deficiency

Gene: SIX3

Red List (low evidence)

SIX3 (SIX homeobox 3)
EnsemblGeneIds (GRCh38): ENSG00000138083
EnsemblGeneIds (GRCh37): ENSG00000138083
OMIM: 603714, Gene2Phenotype
SIX3 is in 12 panels

1 review

Paul De Fazio (Victorian Clinical Genetics Services)

Red List (low evidence)

Two children with combined pituitary hormone deficiency and thin pituitary stalk from a single family were found to be doubly heterozygous for missense variants in SIX3 and POU1F1. A third affected sibling was not available for testing. Two other siblings without pituitary hormone deficiency were not doubly heterozygous for the SIX3 and POU1F1 variants. The SIX3 variant has 46 heterozygotes in gnomAD; the POU1F1 variant is novel.

Functional testing showed the SIX3 variant has weaker activation activity than wild type. Six3 and Pou1f1 doubly heterozygous mice were shown to have abnormal pituitary and palate morphology and reduced viability.
Created: 1 Sep 2022, 6:54 a.m. | Last Modified: 1 Sep 2022, 6:54 a.m.
Panel Version: 0.26

Mode of inheritance
Other

Phenotypes
Non-acquired combined pituitary hormone deficiency MONDO:0018762

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Red
  • Genomics England PanelApp
Phenotypes
  • Holoprosencephaly 2 (157170)
  • Non-acquired combined pituitary hormone deficiency MONDO:0018762
OMIM
603714
Clinvar variants
Variants in SIX3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

1 Sep 2022, Gel status: 1

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: six3 has been classified as Red List (Low Evidence).

1 Sep 2022, Gel status: 1

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: SIX3 were changed from Holoprosencephaly 2 (157170); Non-acquired combined pituitary hormone deficiency MONDO:0018762 to Holoprosencephaly 2 (157170); Non-acquired combined pituitary hormone deficiency MONDO:0018762

1 Sep 2022, Gel status: 1

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: SIX3 were changed from Holoprosencephaly 2 (157170) to Holoprosencephaly 2 (157170); Non-acquired combined pituitary hormone deficiency MONDO:0018762

1 Sep 2022, Gel status: 1

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: SIX3 were set to

13 Jul 2020, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Seb Lunke (Victorian Clinical Genetics Services)

gene: SIX3 was added gene: SIX3 was added to Pituitary hormone deficiency. Sources: Genomics England PanelApp,Expert Review Red Mode of inheritance for gene: SIX3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: SIX3 were set to Holoprosencephaly 2 (157170)