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Fetal anomalies

Gene: SIRT6

Amber List (moderate evidence)
SIRT6 (sirtuin 6)
EnsemblGeneIds (GRCh38): ENSG00000077463
EnsemblGeneIds (GRCh37): ENSG00000077463
OMIM: 606211, Gene2Phenotype
SIRT6 is in 1 panel

4 reviews

Arina Puzriakova (Genomics England Curator)

I don't know

Amber rating has been maintained, inline with the recent review by the R21 Clinical Oversight Group.
Created: 5 Sep 2025, 4:41 p.m. | Last Modified: 5 Sep 2025, 4:41 p.m.
Panel Version: 6.29
Created: 5 Sep 2025, 4:41 p.m.
Last Modified: 5 Sep 2025, 4:41 p.m.
Panel version: 6.29

Natalie Canham (Liverpool Women's Hospital)

I don't know

This gene and phenotype were reviewed during meetings in June & July 2025. The meetings included representatives of the North Thames and Central & South R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Natalie Chandler & Elizabeth Scotchman (North Thames GLH), Natalie Bibb, Stephanie Allen & Sarah Graham (Central & South GLH) and Alice Gardham, Esther Kinning, Vicki Harrison, Anna DeBurca, Natalie Canham, Elizabeth Wall, Sunayna Best, Soo-Mi Park & Sahar Mansour (R21 Clinical Oversight Group).
Created: 5 Sep 2025, 4:31 p.m. | Last Modified: 5 Sep 2025, 4:31 p.m.
Panel Version: 6.28
single paper (from 2018), one family, four fetuses. The other paper is about monkeys
Created: 5 Sep 2025, 2:55 p.m. | Last Modified: 5 Sep 2025, 2:55 p.m.
Panel Version: 6.24

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder, MONDO:0700092

Publications

Created: 5 Sep 2025, 2:55 p.m.
Last Modified: 5 Sep 2025, 2:55 p.m.
Panel version: 6.28

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are four foetuses from a single family and several pieces of functional evidence available in support of the association. This gene is tagged for expert review from the NHS Genomic Medicine Service to decide whether the available evidence is sufficient for promotion to green rating on the next update.
Created: 15 Apr 2025, 9:38 a.m. | Last Modified: 15 Apr 2025, 9:39 a.m.
Panel Version: 5.93
As reviewed by Dmitrijs Rots, PMID:29555651 reported a family with four consecutive cases of late foetal loss with gestational ages between 17 and 35 weeks. The foetuses showed prenatal abnormalities including intrauterine growth restriction (IUGR), microcephaly, craniofacial anomalies, sex reversal in male foetuses, and congenital heart defects. A homozygous inactivating variant in SIRT6 gene (c.187G > C; p.(Asp63His)) was identified by WES in the four foetuses. There is also functional data available from in vitro studies, SIRT6 D63H mouse embryonic stem cells and human induced pluripotent stem cells (iPSCs) derived from D63H homozygous foetuses.

There is also functional evidence available from several other studies including PMID:30135584, where CRISPR-Cas9-based approach was used to generate a SIRT6-null cynomolgus monkey (Macaca fascicularis) model. SIRT6-deficient monkeys died hours after birth and exhibited severe prenatal developmental retardation.

This gene has not been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Created: 15 Apr 2025, 9:34 a.m. | Last Modified: 15 Apr 2025, 9:34 a.m.
Panel Version: 5.90

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Fetal anomaly, HP:0034057

Publications

Created: 15 Apr 2025, 9:34 a.m.
Last Modified: 15 Apr 2025, 9:39 a.m.
Panel version: 5.90

Dmitrijs Rots (Children's Clinical University Hospital)

Green List (high evidence)

The paper describes:"Here, we demonstrate that a homozygous inactivating mutation in the histone deacetylase SIRT6 results in severe congenital anomalies and perinatal lethality in four affected fetuses. " + functional data --> enough evidence for the green rating
Sources: Literature
Created: 9 Oct 2024, 8:04 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
PMID: 29555651

Created: 9 Oct 2024, 8:04 a.m.

Panel version: 4.198

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Fetal anomaly, HP:0034057
  • Neurodevelopmental disorder, MONDO:0700092
OMIM
606211
Clinvar variants
Variants in SIRT6
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

8 Sep 2025, Gel status: 2

Removed Tag, Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_25_ promote_green was removed from gene: SIRT6. Tag Q2_25_expert_review was removed from gene: SIRT6.

5 Sep 2025, Gel status: 2

Set Phenotypes, Set publications

Arina Puzriakova (Genomics England Curator)

Added phenotypes Neurodevelopmental disorder, MONDO:0700092 for gene: SIRT6 Publications for gene: SIRT6 were updated from 29555651; 30135584 to 30135584; 29555651

15 Apr 2025, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: sirt6 has been classified as Amber List (Moderate Evidence).

15 Apr 2025, Gel status: 0

Added Tag, Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q2_25_ promote_green tag was added to gene: SIRT6. Tag Q2_25_expert_review tag was added to gene: SIRT6.

15 Apr 2025, Gel status: 0

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: SIRT6 were changed from PMID: 29555651 to Fetal anomaly, HP:0034057

15 Apr 2025, Gel status: 0

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: SIRT6 were set to

9 Oct 2024, Gel status: 0

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

Dmitrijs Rots (Children's Clinical University Hospital)

gene: SIRT6 was added gene: SIRT6 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SIRT6 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SIRT6 were set to PMID: 29555651 Penetrance for gene: SIRT6 were set to Complete Review for gene: SIRT6 was set to GREEN