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Intellectual disability

Gene: PGBD5

Amber List (moderate evidence)
PGBD5 (piggyBac transposable element derived 5)
EnsemblGeneIds (GRCh38): ENSG00000177614
EnsemblGeneIds (GRCh37): ENSG00000177614
OMIM: 616791, Gene2Phenotype
PGBD5 is in 4 panels

2 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: As reviewed by Karen Stals, there are ten patients from five unrelated families reported with biallelic PGBD5 variants and neurodevelopmental disorder. Severe developmental delay/ intellectual disability was reported in all ten patients. Hence, this gene can be promoted to green rating in the next GMS update.
Created: 28 Apr 2026, 11:01 a.m. | Last Modified: 28 Apr 2026, 11:22 a.m.
Panel Version: 9.400
PMID:41533792 (2026) reported the identification of genetic variants in PGBD5 gene using GeneMatcher in ten individuals from five unrelated consanguineous families. Exome sequencing was used to identify distinct homozygous PGBD5 variants segregating with the affected family members and this was confirmed by Sanger sequencing. These affected children shared conserved clinical phenotypes across neurodevelopmental and motor domains.

Neurodevelopmental features included intellectual disability and developmental delay (ID/DD; ten of ten), epilepsy (nine of nine), limited or no speech (nine of nine), autism spectrum disorder, or social delay (ASD; four of six). Prominent motor features included axial hypotonia (nine of nine), increased peripheral tone (seven of nine) or decreased peripheral tone (two of nine), increased tendon reflexes (five of nine), or decreased tendon reflexes (four of nine). Other observed neurological phenotypes include spasticity that mainly affected the lower limbs (five of nine), intermittent dystonia (three of ten), and ataxia (seven of ten).

There is also evidence available from Pgbd5-null mice, which were runted and had significantly smaller brains compared to wildtype. Mutant mice showed increased locomotor activity, reduced anxiety-like behavior, impaired motor coordination, increased susceptibility to seizures, and decreased cortical volume on brain MRI. Analysis of neurons derived from Pgbd5-null mouse brains showed reduced DNA breakage and repair in postmitotic neuronal precursors during cortical development compared to controls.

This gene has already been associated with relevant phenotype in OMIM (MIM #41533792, last accessed 28 April 2026), but not yet in Gene2Phenotype.
Created: 28 Apr 2026, 10:46 a.m. | Last Modified: 28 Apr 2026, 10:46 a.m.
Panel Version: 9.397

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with seizures, hypotonia, and variable spasticity, OMIM:621482; neurodevelopmental disorder with seizures, hypotonia, and variable spasticity, MONDO:0980968

Publications

Created: 28 Apr 2026, 10:31 a.m.
Last Modified: 28 Apr 2026, 11:22 a.m.
Panel version: 9.398

Karen Stals (Royal Devon and Exeter Hospital)

Green List (high evidence)

Zapater et al. 2026 PMID:41533792 report 5 families with homozygous loss of function variants in PGBD5 co-segregating in two affected siblings in each family (variants identified via whole exome sequencing). Authors show that PGBD5 contributes to normal brain development in mice and humans.
Sources: Literature
Created: 22 Apr 2026, 10:45 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Seizures; global developmental delay; spasticity; hypotonia

Publications

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

Created: 22 Apr 2026, 10:45 a.m.

Panel version: 9.389

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Neurodevelopmental disorder with seizures, hypotonia, and variable spasticity, OMIM:621482
  • neurodevelopmental disorder with seizures, hypotonia, and variable spasticity, MONDO:0980968
Tags
Q2_26_promote_green Q2_26_NHS_review
OMIM
616791
Clinvar variants
Variants in PGBD5
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

28 Apr 2026, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: pgbd5 has been classified as Amber List (Moderate Evidence).

28 Apr 2026, Gel status: 0

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: PGBD5 were changed from Seizures; global developmental delay; spasticity; hypotonia to Neurodevelopmental disorder with seizures, hypotonia, and variable spasticity, OMIM:621482; neurodevelopmental disorder with seizures, hypotonia, and variable spasticity, MONDO:0980968

28 Apr 2026, Gel status: 0

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: PGBD5 were set to PMID: 41533792

28 Apr 2026, Gel status: 0

Added Tag, Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q2_26_promote_green tag was added to gene: PGBD5. Tag Q2_26_NHS_review tag was added to gene: PGBD5.

22 Apr 2026, Gel status: 0

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

Karen Stals (Royal Devon and Exeter Hospital)

gene: PGBD5 was added gene: PGBD5 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: PGBD5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PGBD5 were set to PMID: 41533792 Phenotypes for gene: PGBD5 were set to Seizures; global developmental delay; spasticity; hypotonia Penetrance for gene: PGBD5 were set to Complete Review for gene: PGBD5 was set to GREEN gene: PGBD5 was marked as current diagnostic