Intellectual disability
Gene: PI4K2A

PI4K2A (phosphatidylinositol 4-kinase type 2 alpha)
EnsemblGeneIds (GRCh38): ENSG00000155252
EnsemblGeneIds (GRCh37): ENSG00000155252
OMIM: 609763, Gene2Phenotype
PI4K2A is in 3 panels

3 reviews

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Created: 24 Feb 2025, 6:15 p.m. | Last Modified: 24 Feb 2025, 6:15 p.m.

Panel Version: 8.97

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Created: 24 Feb 2025, 6:15 p.m.
Last Modified: 24 Feb 2025, 6:15 p.m.
Panel version: 8.97

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: As reviewed by Tracy Lester, there are four unrelated cases reported with global developmental delay and/ or profound intellectual disability. Hence, this gene should be promoted to green rating in the next GMS update.
Created: 5 Nov 2024, 12:14 p.m. | Last Modified: 5 Nov 2024, 12:14 p.m.

Panel Version: 8.13

Comment on phenotypes: This gene has been associated with relevant phenotype in OMIM (MIM #620732), but not yet in Gene2Phenotype.
Created: 5 Nov 2024, 12:11 p.m. | Last Modified: 5 Nov 2024, 12:11 p.m.

Panel Version: 8.12

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, OMIM:620732

Created: 5 Nov 2024, 12:06 p.m.
Last Modified: 5 Nov 2024, 12:06 p.m.
Panel version: 8.9

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

At least three cases have been reported with biallelic variants in this gene and a neurodevelopmental disorder
35880319 - Two patients with PI4K2A deficiency (homozygous variants) were identified by exome sequencing, presenting with developmental and epileptic-dyskinetic encephalopathy. Neuroimaging showed corpus callosum dysgenesis, diffuse white matter volume loss, and hypoplastic vermis. In addition to NDD, we observed recurrent infections and death at toddler age.
30564627 - We report a family of Saudi Arabian ancestry with two children presenting with global developmental delay, dystonia, disturbed sleep, and heat intolerance. By genome sequencing, we identified a nonsense variant in the first exon of PI4K2A that was homozygous in both affected individuals and was absent from, or heterozygous in, seven unaffected siblings.
32418222 - a homozygous missense variant of uncertain significance was suggested to be responsible for some features in a case with NDD and metabolic cutis laxa.
Sources: NHS GMS
Created: 4 Nov 2024, 4:06 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability; developmental delay; seizures

Publications

Created: 4 Nov 2024, 4:06 p.m.

Panel version: 8.6

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green

Phenotypes

Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, OMIM:620732

OMIM

609763

Clinvar variants

Variants in PI4K2A

Penetrance

unknown

Publications

Panels with this gene

History Filter Activity

25 Feb 2025, Gel status: 3

Removed Tag, Removed Tag

Sarah Leigh (Genomics England Curator)

Tag Q3_24_promote_green was removed from gene: PI4K2A. Tag Q3_24_NHS_review was removed from gene: PI4K2A.

24 Feb 2025, Gel status: 3

Added New Source, Status Update

Sarah Leigh (Genomics England Curator)

Source Expert Review Green was added to PI4K2A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

5 Nov 2024, Gel status: 2