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

3 reviews

Sarah Leigh (Genomics England Curator)

Red List (low evidence)

Comment on list classification: There is not enough evidence for this gene to be rated GREEN at the next major review.
Created: 22 Sep 2022, 12:40 p.m. | Last Modified: 22 Sep 2022, 12:40 p.m.
Panel Version: 2.96
Associated with Holoprosencephaly 2 (OMIM:157170) in OMIM and as definitive Gen2Phen gene for this phenotype. PMID: 35951005 reports a familiy with children with combined pituitary hormone deficiency, who are heterozygous for variants in SIX3 & POU1F1. Heterozygous Six3 variant mouse models reported in the same paper have pituitary gland dysmorphology and incompletely ossified palate.
Created: 22 Sep 2022, 12:39 p.m. | Last Modified: 22 Sep 2022, 12:39 p.m.
Panel Version: 2.95

Eleanor Williams (Genomics England Curator)

Review on behalf of Professor Mehul Dattani, UCL GOS Institute of Child Health/Great Ormond Street Hospital for Children. AD - ?COMBINATION WITH OTHER PITUITARY GENES. Bando H, Brinkmeier ML, Castinetti F, Fang Q, Lee MS, Saveanu A, Albarel F, Dupuis C, Brue T, Camper SA.Hum Mol Genet. 2022 Aug 11:ddac192. doi: 10.1093/hmg/ddac192. Online ahead of print.PMID:35951005
Created: 14 Sep 2022, 4:44 p.m. | Last Modified: 14 Sep 2022, 4:44 p.m.
Panel Version: 2.15

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
HYPOPITUITARISM

Publications

Ivone Leong (Genomics England Curator)

Comment on list classification: Demoted from amber to red. SIX3 is confirmed to be associated with Holoprosencephaly in OMIM and Gene2Phenotype and is a green gene on the Holoprosencephaly gene panel (Version 1.6). However, there is no evidence that patients with Holoprosencephaly with variants in the SIX3 gene has pituitary hormone deficiency.
Created: 14 Dec 2018, 2:26 p.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Red
  • UKGTN
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Holoprosencephaly 2, OMIM:157170
  • alobar holoprosencephaly, MONDO:0019757
OMIM
603714
Clinvar variants
Variants in SIX3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

22 Sep 2022, Gel status: 1

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

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

22 Sep 2022, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: SIX3 were set to 35951005; 34974160; 32796691

22 Sep 2022, Gel status: 1

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: SIX3 were changed from Holoprosencephaly 2,OMIMM157170 to Holoprosencephaly 2, OMIM:157170; alobar holoprosencephaly, MONDO:0019757

22 Sep 2022, Gel status: 1

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: SIX3 were changed from Holoprosencephaly 2 (157170) to Holoprosencephaly 2,OMIMM157170

22 Sep 2022, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: SIX3 were set to 35951005

22 Sep 2022, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: SIX3 were set to

30 Jan 2019, Gel status: 1

Panel promoted to version 1.0

Ivone Leong (Genomics England Curator)

Ivone Leong: Comment on list classification

14 Dec 2018, Gel status: 1

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

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

10 Dec 2018, Gel status: 2

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

Ivone Leong (Genomics England Curator)

gene: SIX3 was added gene: SIX3 was added to Pituitary hormone deficiency. Sources: Radboud University Medical Center, Nijmegen,UKGTN 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)