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Intellectual disability

Gene: GSPT2

Amber List (moderate evidence)
GSPT2 (G1 to S phase transition 2)
EnsemblGeneIds (GRCh38): ENSG00000189369
EnsemblGeneIds (GRCh37): ENSG00000189369
OMIM: 300418, Gene2Phenotype
GSPT2 is in 4 panels

6 reviews

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are now at least 5 unrelated male individuals reported with hemizygous missense variants in GSPT2 and severe ID/DD. These variants were inherited from unaffected mothers. Hence, this gene can be promoted to Green on Intellectual disability, with MOI set to "X-LINKED: hemizygous mutation in males, biallelic mutations in females".
Created: 27 Oct 2026, 12:47 p.m. | Last Modified: 27 Oct 2026, 12:48 p.m.
Panel Version: 11.65
PMID: 41420488 Wei et al., 2026
Study reports 6 male individuals from 6 unrelated families (including 1 fetal case) carrying hemizygous missense variants in GSPT2 with intellectual disability, delayed speech and language development, autism spectrum disorder, epilepsy, or abnormal fetal neurodevelopment. Severe ID / learning disability & DD were present in 5/5 individuals. Brain malformations and seizures were reported in 3 probands.
Functional evidence: Structural molecular modeling revealed significant deleterious effects of the identified variants. GSPT2 is preferentially enriched in the brain and cerebellum compared with other tissues. Transcriptomics revealed that GABAergic and calcium-signaling-related genes were significantly downregulated in GSPT2-deficient cells.

GSPT2 is not yet associated with a disease entity in OMIM (accessed 27th Oct 2026).
Created: 27 Oct 2026, 12:39 p.m. | Last Modified: 27 Oct 2026, 12:47 p.m.
Panel Version: 11.65

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

Created: 27 Oct 2026, 12:39 p.m.
Last Modified: 27 Oct 2026, 12:48 p.m.
Panel version: 11.62

Arina Puzriakova (Genomics England Curator)

Conference poster (Genomics of Rare Disease 2021) - 'Exome-wide NGS analysis within a diagnostic time frame: promise or pitfall' by Abbott et al, University Medical Center Groningen, Netherlands (abstract also accepted for poster at ESHG 2021) -

WES revealed a c.872A>G variant in the GSPT2 gene in a patient with severe DD, severe epilepsy, acquired microcephaly, central and obstructive apnea, oedema, and mild aspecific dysmorphic features.

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Maintaining Red rating as this is unpublished data, but added a watchlist tag to review possible future evidence of SNVs in disease.
Created: 30 Mar 2021, 1:10 p.m. | Last Modified: 30 Mar 2021, 1:10 p.m.
Panel Version: 3.981
Created: 30 Mar 2021, 1:10 p.m.
Last Modified: 30 Mar 2021, 1:10 p.m.
Panel version: 3.981

Louise Daugherty (Genomics England Curator)

Red List (low evidence)

Comment on list classification: After internal and external review, it was agreed this gene should be demoted from Green to Red
Created: 12 Sep 2018, 1:24 p.m.
In view of recent external expert Green review this gene was reaccessed. Given the current information in the literature, one report of a duplication (as a candidate ID gene) and a microdeletion report (encompassing other genes), probable DD gene for XL intellectual disability, there are also some cases in Decipher but none are confirmed as pathogenic / explain the phenotype in full. As this is currently a Green gene, past onto clinical team for consideration to downgrade gene to Red.
Created: 9 Aug 2018, 1:06 p.m.
Comment on publications: added publications to support association to ID. PMID: 28414775 (2017) reports Xp11.22 deletions encompassing CENPVL1, CENPVL2, MAGED1 and GSPT2 as a cause of syndromic X-linked intellectual disability. PMID: 20655035 (2010) Fine-scale survey of X chromosome copy number variants and indels underlying intellectual disability. They identified pathogenic copy number variants in 10% of families, with mutations ranging from 2 kb to 11 Mb in size. They identified a whole-gene duplication of GSPT2 and confirmed the direct tandem orientation of the duplicated region in one family.
Created: 9 Aug 2018, 12:29 p.m.
Created: 9 Aug 2018, 12:29 p.m.

Panel version: 2.333

Zornitza Stark (Australian Genomics)

I don't know

I can't find published evidence other than micordeletion reports (encompassing other genes) to support the inclusion of this gene
Created: 18 Jun 2018, 6:59 a.m.
Created: 18 Jun 2018, 6:59 a.m.

Panel version: 2.104

Caroline Wright (Sanger)

Green List (high evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
XL INTELLECTUAL DISABILITY

Publications

  • 0

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

Lu Raymond (university of cambridge )

Green List (high evidence)

Created: 23 Feb 2016, 11 a.m.

Panel version: 0.306

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Amber
Phenotypes
  • neurodevelopmental disorder, MONDO:0700092
Tags
Q4_26_promote_green
OMIM
300418
Clinvar variants
Variants in GSPT2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

27 Oct 2026, Gel status: 2

Entity classified by Genomics England curator

Ida Ertmanska (Genomics England Curator)

Gene: gspt2 has been classified as Amber List (Moderate Evidence).

27 Oct 2026, Gel status: 1

Set Phenotypes

Ida Ertmanska (Genomics England Curator)

Phenotypes for gene: GSPT2 were changed from XL INTELLECTUAL DISABILITY to neurodevelopmental disorder, MONDO:0700092

27 Oct 2026, Gel status: 1

Set publications

Ida Ertmanska (Genomics England Curator)

Publications for gene: GSPT2 were set to 28414775; 20655035

27 Oct 2026, Gel status: 1

Removed Tag, Added Tag

Ida Ertmanska (Genomics England Curator)

Tag watchlist was removed from gene: GSPT2. Tag Q4_26_promote_green tag was added to gene: GSPT2.

30 Mar 2021, Gel status: 1

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist tag was added to gene: GSPT2.

12 Sep 2018, Gel status: 1

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: gspt2 has been classified as Red List (Low Evidence).

9 Aug 2018, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: GSPT2 were set to 28414775; 20655035

12 Mar 2018, Gel status: 3

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

GSPT2 was created by ellenmcdonagh

13 Nov 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

GSPT2 was added to Intellectual disabilitypanel. Sources: Expert Review Green