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Intellectual disability

Gene: PPP2R1A

Green List (high evidence)
PPP2R1A (protein phosphatase 2 scaffold subunit Aalpha)
EnsemblGeneIds (GRCh38): ENSG00000105568
EnsemblGeneIds (GRCh37): ENSG00000105568
OMIM: 605983, Gene2Phenotype
PPP2R1A is in 5 panels

4 reviews

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

PMID: 33106617 Lenaerts et al., 2021
Report of 30 individuals with 16 different de novo variants in PPP2R1A. Shared phenotype: developmental delay (97%), hypotonia (93%), hypermobile joints (58%), CC hypoplasia/agenesis (56%), epilepsy (38%), macrocephaly (38%). Macrocephaly and epilepsy were mutually exclusive. Intellectual disability ranged from mild to severe, based on functional effects of each variant.

Functional evidence: HEK293T cells transfected with PPP2R1A mutants - variants from patients with less severe ID, no seizures, and sometimes macrocephaly typically showed normal B55α and STRN3 binding, while more severe ID, seizures, and sometimes microcephaly correlated with lost B55α binding and increased STRN3 binding.

PPP2R1A is now associated with AD Houge-Janssens syndrome 2, OMIM:616362 (OMIM accessed 13th Mar 2026). PPP2R1A is Definitve in ClinGen for an AD complex neurodevelopmental disorder (Nov 2022).
Created: 13 Mar 2026, 11:37 a.m. | Last Modified: 13 Mar 2026, 11:57 a.m.
Panel Version: 9.304

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Houge-Janssens syndrome 2, OMIM:616362; Houge-Janssens syndrome 2, MONDO:0014605

Publications

Created: 13 Mar 2026, 11:37 a.m.
Last Modified: 13 Mar 2026, 11:57 a.m.
Panel version: 9.303

Caroline Wright (Sanger)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
INTELLECTUAL DISABILITY

Publications

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

Panel version: 0

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf . Main mutation mechanism : Dominant negative
Created: 27 Jul 2017, 8:07 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; GEL_ID_green_20160217; neuro_20160418_strict; Dominant negative. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 1:10 p.m.

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

Publications

Mode of pathogenicity
Other - please provide details in the comments

Created: 2 Aug 2017, 9:48 p.m.

Panel version: 1.354

Lu Raymond (university of cambridge )

Green List (high evidence)

Created: 23 Feb 2016, 10:54 a.m.

Panel version: 0.306

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
Phenotypes
  • Houge-Janssens syndrome 2, OMIM:616362
  • Houge-Janssens syndrome 2, MONDO:0014605
OMIM
605983
Clinvar variants
Variants in PPP2R1A
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

13 Mar 2026, Gel status: 3

Set Phenotypes

Ida Ertmanska (Genomics England Curator)

Phenotypes for gene: PPP2R1A were changed from INTELLECTUAL DISABILITY to Houge-Janssens syndrome 2, OMIM:616362; Houge-Janssens syndrome 2, MONDO:0014605

13 Mar 2026, Gel status: 3

Set publications

Ida Ertmanska (Genomics England Curator)

Publications for gene: PPP2R1A were set to 25533962

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)

PPP2R1A was created by ellenmcdonagh

13 Nov 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

PPP2R1A was added to Intellectual disabilitypanel. Sources: Expert Review Green