PGBD5

Chr 1

piggyBac transposable element derived 5

Also known as: NEDSHS

NCBI Gene: 79605 ENSG00000177614 UniProt: Q8N414

PGBD5 encodes a transposase that mediates sequence-specific genomic rearrangements and can induce gene inactivation. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with seizures, hypotonia, and variable spasticity. The gene shows low constraint to loss-of-function variation (pLI 0.002, LOEUF 0.708), consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

LOEUF 0.71

Clinical Summary— PGBD5

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

5 unique Pathogenic / Likely Pathogenic of 18 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.71LOEUF

pLI 0.002

Z-score 2.54

OE 0.39 (0.23–0.71)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.35Z-score

OE missense 0.78 (0.70–0.87)

225 obs / 289.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.23–0.71)

0≤0.351.4

Missense OE?0.78 (0.70–0.87)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 8 / 20.4Missense obs/exp: 225 / 289.8Syn Z: -0.55

ClinVar Variant Classifications

18 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Benign2

Benign4

Pathogenic

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	0	1	0	5
Likely Pathogenic	0	0	0	0	0
VUS	0	0	0	0	0
Likely Benign	0	0	0	2	2
Benign	0	2	0	2	4
Total	4	2	1	4	11

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

View in ClinVar →

39 pathogenic / likely-pathogenic (of 47) ClinVar copy-number / structural variants overlap PGBD5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →