Pituitary hormone deficiency
Gene: SIX3EnsemblGeneIds (GRCh38): ENSG00000138083
EnsemblGeneIds (GRCh37): ENSG00000138083
OMIM: 603714, Gene2Phenotype
SIX3 is in 12 panels
1 review
Paul De Fazio (Victorian Clinical Genetics Services)
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
-
- Holoprosencephaly and septo-optic dysplasia
- Anophthalmia_Microphthalmia_Coloboma
- Fetal anomalies
- Clefting disorders
- Additional findings_Paediatric
- Mendeliome
- BabyScreen+ newborn screening
- Polymicrogyria and Schizencephaly
- Pituitary hormone deficiency
- Intellectual disability syndromic and non-syndromic
- Callosome
- Genetic Epilepsy
History Filter Activity
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Gene: six3 has been classified as Red List (Low Evidence).
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
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
Set publications
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Publications for gene: SIX3 were set to
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)