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Fetal anomalies

Gene: PPP3CA

Amber List (moderate evidence)
PPP3CA (protein phosphatase 3 catalytic subunit alpha)
EnsemblGeneIds (GRCh38): ENSG00000138814
EnsemblGeneIds (GRCh37): ENSG00000138814
OMIM: 114105, Gene2Phenotype
PPP3CA is in 5 panels

2 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

I don't know

Condition causing multiple congenital anomalies is postulated to be due to GoF variants. However, only 2 individuals reported.

DEE postulated to be due to LoF variants, and presents post-natally.
Created: 2 Feb 2022, 4:26 a.m. | Last Modified: 8 Feb 2022, 12:32 a.m.
Panel Version: 0.3163

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development MIM#618265

Created: 2 Feb 2022, 4:26 a.m.
Last Modified: 8 Feb 2022, 12:32 a.m.
Panel version: 0.3094

Belinda Chong (Victorian Clinical Genetics Services)

I don't know

ACCIID is characterized by arthrogryposis, cleft palate, craniosynostosis, micrognathia, short stature, and impaired intellectual development. Seizures and bony abnormalities (severe slenderness of the ribs and tubular bones and perinatal fractures) have been observed. Developmental and epileptic encephalopathy-91 (DEE91) is characterized by delayed psychomotor development apparent in infancy and resulting in severely to profoundly impaired intellectual development with poor or absent speech. Most patients never achieve independent walking. Patients typically have onset of refractory multifocal seizures between the first weeks and years of life, and some may show developmental regression. Additional features, such as hypotonia and cortical visual impairment, are more variable.

PMID 29432562
In 2 patients with ACCIID, Mizuguchi et al. (2018) identified de novo heterozygous mutations in the autoinhibitory domain of the PPP3CA gene. The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. Using a yeast model, the mutations were found to be constitutively activating.

PMID 28942967
In 6 unrelated patients with DEE91, Myers et al. (2017) identified 5 different de novo heterozygous mutations in the PPP3CA gene. The patients were ascertained from several large independent cohorts of patients with neurodevelopmental or seizure disorders (see, e.g., the EuroEPINOMICS-RES Consortium et al., 2014 and Zhu et al., 2015); the mutations were found by exome sequencing and confirmed by Sanger sequencing. There was 1 nonsense mutation and 4 missense mutations, 3 of which occurred in the catalytic domain.
Created: 1 Feb 2022, 2:59 a.m. | Last Modified: 1 Feb 2022, 2:59 a.m.
Panel Version: 0.3031

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development MIM#618265; Developmental and epileptic encephalopathy 91 617711

Publications

Variants in this GENE are reported as part of current diagnostic practice

Created: 1 Feb 2022, 2:59 a.m.
Last Modified: 1 Feb 2022, 2:59 a.m.
Panel version: 0.3031

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Genomics England PanelApp
Phenotypes
  • Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development MIM#618265
OMIM
114105
Clinvar variants
Variants in PPP3CA
Penetrance
None
Publications
Panels with this gene

History Filter Activity

2 Feb 2022, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: ppp3ca has been classified as Amber List (Moderate Evidence).

2 Feb 2022, Gel status: 2

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: PPP3CA were changed from Severe Neurodevelopmental Disease with Seizures to Arthrogryposis, cleft palate, craniosynostosis, and impaired intellectual development MIM#618265

2 Feb 2022, Gel status: 2

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: PPP3CA were set to

24 Oct 2021, Gel status: 2

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

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: PPP3CA was added gene: PPP3CA was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: PPP3CA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: PPP3CA were set to Severe Neurodevelopmental Disease with Seizures