PGBD5

Chr 1AR

piggyBac transposable element derived 5

Also known as: NEDSHS

NCBI Gene: 79605ENSG00000177614UniProt: Q8N414

The piggyBac family of proteins, found in diverse animals, are transposases related to the transposase of the canonical piggyBac transposon from the moth, Trichoplusia ni. This family also includes genes in several genomes, including human, that appear to have been derived from the piggyBac transposons. This gene belongs to the subfamily of piggyBac transposable element derived (PGBD) genes. The PGBD proteins appear to be novel, with no obvious relationship to other transposases, or other known protein families. [provided by RefSeq, May 2010]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with seizures, hypotonia, and variable spasticityMIM #621482
AR
56
ClinVar variants
44
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PGBD5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
44 Pathogenic / Likely Pathogenic· 6 VUS of 56 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.71LOEUF
pLI 0.002
Z-score 2.54
OE 0.39 (0.23–0.71)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.35Z-score
OE missense 0.78 (0.70–0.87)
225 obs / 289.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.39 (0.23–0.71)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.70–0.87)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 8 / 20.4Missense obs/exp: 225 / 289.8Syn Z: -0.55

ClinVar Variant Classifications

56 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic2
VUS6
Likely Benign2
Benign4
42
Pathogenic
2
Likely Pathogenic
6
VUS
2
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
40
0
42
Likely Pathogenic
0
0
2
0
2
VUS
0
0
6
0
6
Likely Benign
0
0
0
2
2
Benign
0
2
0
2
4
Total2248456

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PGBD5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with seizures, hypotonia, and variable spasticity

MIM #621482

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Epigenetic targeting of PGBD5-dependent DNA damage in SMARCB1-deficient sarcomas.
Kazansky Y et al.·J Clin Invest
2025
CHST3, PGBD5, and SLIT2 can be identified as potential genes for the diagnosis and treatment of osteoporosis and sarcopenia.
Yang X et al.·Sci Rep
2025
Emerging functions of DNA transposases and oncogenic mutators in childhood cancer development.
Henssen AG et al.·JCI Insight
2018Review
Unraveling shared diagnostic genes and cellular microenvironmental changes in endometriosis and recurrent implantation failure through multi-omics analysis.
Qin D et al.·Sci Rep
2025
Forward genetic screen of human transposase genomic rearrangements.
Henssen AG et al.·BMC Genomics
2016
The C-terminal Domain of piggyBac Transposase Is Not Required for DNA Transposition.
Helou L et al.·J Mol Biol
2021
Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies.
Broce I et al.·PLoS Med
2018Meta-analysis
Based on different immune responses under the glucose metabolizing type of papillary thyroid cancer and the response to anti-PD-1 therapy.
Xie W et al.·Front Immunol
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools