PGBD5

Summary

PGBD5 (piggyBac transposable element derived 5, HGNC:19405) is a protein-coding gene on chromosome 1q42.13, encoding PiggyBac transposable element-derived protein 5 (Q8N414). Transposase that mediates sequence-specific genomic rearrangements.

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.

Source: NCBI Gene 79605 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 16 total — 5 pathogenic
• Phenotypes (HPO): 38
• MANE Select transcript: NM_001258311

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19405
Approved symbol	PGBD5
Name	piggyBac transposable element derived 5
Location	1q42.13
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp761A0620, FLJ11413
Ensembl gene	ENSG00000177614
Ensembl biotype	protein_coding
OMIM	616791
Entrez	79605

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000391860, ENST00000525115, ENST00000530424, ENST00000916427, ENST00000966559

RefSeq mRNA: 1 — MANE Select: NM_001258311 NM_001258311

CCDS: CCDS81430

Canonical transcript exons

ENST00000391860 — 7 exons

Exon	Start	End
ENSE00001262319	230337108	230337288
ENSE00001262328	230350958	230351092
ENSE00001440853	230314490	230323620
ENSE00001509920	230425598	230426332
ENSE00003578698	230325310	230325415
ENSE00003589106	230332844	230333041
ENSE00003612230	230356894	230357321

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 94.75.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3204 / max 43.4490, expressed in 408 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17934	1.3204	408

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	94.75	gold quality
entorhinal cortex	UBERON:0002728	94.56	gold quality
middle temporal gyrus	UBERON:0002771	94.24	gold quality
postcentral gyrus	UBERON:0002581	93.69	gold quality
superior frontal gyrus	UBERON:0002661	93.25	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.20	gold quality
parietal lobe	UBERON:0001872	93.06	gold quality
Brodmann (1909) area 10	UBERON:0013541	92.93	gold quality
orbitofrontal cortex	UBERON:0004167	92.71	gold quality
cerebellar vermis	UBERON:0004720	92.70	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.48	gold quality
paraflocculus	UBERON:0005351	91.70	gold quality
prefrontal cortex	UBERON:0000451	91.50	gold quality
CA1 field of hippocampus	UBERON:0003881	90.85	gold quality
endothelial cell	CL:0000115	90.71	gold quality
frontal cortex	UBERON:0001870	90.63	gold quality
primary visual cortex	UBERON:0002436	90.14	gold quality
occipital lobe	UBERON:0002021	89.87	gold quality
neocortex	UBERON:0001950	89.51	gold quality
cerebral cortex	UBERON:0000956	89.36	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.82	gold quality
right frontal lobe	UBERON:0002810	88.65	gold quality
Ammon’s horn	UBERON:0001954	88.42	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.36	gold quality
cerebellum	UBERON:0002037	87.98	gold quality
temporal lobe	UBERON:0001871	87.93	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.80	gold quality
cerebellar cortex	UBERON:0002129	87.75	gold quality
cerebellar hemisphere	UBERON:0002245	87.67	gold quality
telencephalon	UBERON:0001893	87.01	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.14

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 6)

• DNA transposition catalyzed by PGBD5 in human cells occurs genome-wide, with precise transposon excision and preference for insertion at TTAA sites. (PMID:26406119)
• Previously undefined genomic rearrangements in rhabdoid tumors involved PGBD5-specific signal (PSS) sequences at their breakpoints and recurrently inactivated tumor-suppressor genes. PGBD5 physically associated with genomic PSS sequences mediating PGBD5-induced DNA rearrangements in rhabdoid tumor cells. In immortalized cells, PGBD5 sufficed for transformation via specific catalytic residues in the transposase domain. (PMID:28504702)
• The C-terminal Domain of piggyBac Transposase Is Not Required for DNA Transposition. (PMID:33450253)
• Cognate restriction of transposition by piggyBac-like proteins. (PMID:34232995)
• Childhood cancer mutagenesis caused by transposase-derived PGBD5. (PMID:38517960)
• Knockdown of PGBD5 inhibits the malignant progression of glioma through upregulation of the PPAR pathway. (PMID:38577941)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pgbd5	ENSDARG00000011042
mus_musculus	Pgbd5	ENSMUSG00000050751
rattus_norvegicus	Pgbd5	ENSRNOG00000026791

Protein

Protein identifiers

PiggyBac transposable element-derived protein 5 — Q8N414 (reviewed: Q8N414)

Alternative names: PiggyBac domain-related protein 5, PiggyBac transposase 5

All UniProt accessions (1): Q8N414

UniProt curated annotations — full annotation on UniProt →

Function. Transposase that mediates sequence-specific genomic rearrangements. Can induce genomic rearrangements that inactivate the HPRT1 gene.

Subcellular location. Nucleus.

Disease relevance. Induces site-specific DNA rearrangements, including intrachromosomal deletions, as well as inversions, duplications and translocations, in rhabdoid tumors that share developmental origin with cells that normally express PGBD5, even though these tumors may not exhibit apparent widespread genomic instability. This activity recurrently targets regulatory elements and tumor suppressor genes and promotes cell transformation.

Miscellaneous. Has been domesticated very early in vertebrate evolution, approximately 500 million years ago, in the common ancestor of cephalochordates and vertebrates.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N414-1	1	yes
Q8N414-2	2

RefSeq proteins (1): NP_001245240* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029526	PGBD	Domain
IPR042423	PGBD5	Family

Pfam: PF13843

UniProt features (33 total): mutagenesis site 23, compositionally biased region 3, sequence conflict 3, chain 1, region of interest 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N414-F1	81.78	0.60

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 521

Mutagenesis-validated functional residues (23):

Position	Phenotype
261	decreased dna transposase activity.
263	loss of dna transposase activity and of cell transforming activity.
272	no effect on dna transposase activity.
274	no effect on dna transposase activity.
305	decreased dna transposase activity.
310	no effect on dna transposase activity.
313	no effect on dna transposase activity.
353	decreased dna transposase activity.
354	no effect on dna transposase activity.
356	no effect on dna transposase activity.
372	no effect on dna transposase activity.
434	no effect on dna transposase activity, nor on cell transforming activity.
442	no effect on dna transposase activity, nor on cell transforming activity.
455	loss of dna transposase activity. no effect on cell transforming activity.
456	no effect on dna transposase activity.
494	no effect on dna transposase activity.
508	no effect on dna transposase activity.
513	no effect on dna transposase activity.
518	no effect on dna transposase activity.
519	no effect on dna transposase activity.
237	loss of dna transposase activity and of cell transforming activity.
244	no effect on dna transposase activity.
257	decreased dna transposase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 94 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GOZGIT_ESR1_TARGETS_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, WEI_MYCN_TARGETS_WITH_E_BOX, GNF2_TM4SF2, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, ROSS_AML_WITH_PML_RARA_FUSION, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GRYDER_PAX3FOXO1_TOP_ENHANCERS, SMID_BREAST_CANCER_LUMINAL_B_DN, GOBP_DNA_METABOLIC_PROCESS, GOBP_DNA_RECOMBINATION, GCACTTT_MIR175P_MIR20A_MIR106A_MIR106B_MIR20B_MIR519D

GO Biological Process (2): non-replicative DNA transposition (GO:0098038), transposition (GO:0032196)

GO Molecular Function (4): endonuclease activity (GO:0004519), transposase activity (GO:0004803), hydrolase activity (GO:0016787), nuclease activity (GO:0004518)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA transposition	1
cellular process	1
nuclease activity	1
catalytic activity, acting on DNA	1
catalytic activity	1
catalytic activity, acting on a nucleic acid	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3219 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PGBD5	THAP9	Q9H5L6	789
PGBD5	HARBI1	Q96MB7	663
PGBD5	GIN1	Q9NXP7	659
PGBD5	TMEM145	Q8NBT3	585
PGBD5	XKR7	Q5GH72	579
PGBD5	SETMAR	Q53H47	573
PGBD5	PGBD1	Q96JS3	534
PGBD5	PGBD2	Q6P3X8	513
PGBD5	QRICH1	Q2TAL8	508
PGBD5	SACK1C	Q9BQN1	506
PGBD5	RAG1	P15918	497
PGBD5	RBM33	Q96EV2	488
PGBD5	POGK	Q9P215	481
PGBD5	ZBED8	Q8IZ13	478
PGBD5	NAIF1	Q69YI7	476

IntAct

6 interactions, top by confidence:

A	B	Type	Score
RABGGTB	PIPSL	psi-mi:“MI:0914”(association)	0.530
PIP5K1C	SNX4	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
PIP5K1A	SNAPC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): PGBD5 (Affinity Capture-MS), PGBD5 (Affinity Capture-MS), PGBD5 (Affinity Capture-RNA), PGBD5 (Proximity Label-MS), PGBD5 (Affinity Capture-MS), PGBD5 (Affinity Capture-MS), PGBD5 (Affinity Capture-MS), PGBD5 (Affinity Capture-MS), PGBD5 (Affinity Capture-RNA)

ESM2 similar proteins: A0A8I3NFE2, A0JM59, A2RT67, A5PK16, A5PN09, A7Z056, D3YZI9, D7PF45, F1QGZ6, O14757, O15357, O35710, O81360, P36195, P41002, P51944, Q0JCU7, Q32NJ2, Q32NM1, Q5E9N5, Q5F3G0, Q5R5Z6, Q5T447, Q5XGG5, Q6DI92, Q6P549, Q6ZN16, Q7T0L6, Q7TN16, Q7ZUM8, Q80TA6, Q80WG7, Q8AYC9, Q8BRH3, Q8C6M1, Q8K4F8, Q8N414, Q8N6K7, Q8W519, Q94K49

Diamond homologs: D3YZI9, Q8N414

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

16 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	0
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
4690260	NM_001258311.2(PGBD5):c.49G>T (p.Glu17Ter)	Pathogenic
4690261	PGBD5, 1-BP DEL, 509A	Pathogenic
4690262	NM_001258311.2(PGBD5):c.138C>A (p.Tyr46Ter)	Pathogenic
4690263	NM_001258311.2(PGBD5):c.1442_1490del (p.Ile481fs)	Pathogenic
4690264	NM_001258311.2(PGBD5):c.214del (p.Ala72fs)	Pathogenic

SpliceAI

1399 predictions. Top by Δscore:

Variant	Effect	Δscore
1:230325308:A:AC	donor_gain	1.0000
1:230325309:C:CC	donor_gain	1.0000
1:230325309:CTTG:C	donor_gain	1.0000
1:230325413:CTC:C	acceptor_gain	1.0000
1:230332842:AC:A	donor_gain	1.0000
1:230332843:CC:C	donor_gain	1.0000
1:230332843:CCCTG:C	donor_gain	1.0000
1:230337103:CTAA:C	donor_loss	1.0000
1:230337107:C:CG	donor_loss	1.0000
1:230337107:CCTTG:C	donor_gain	1.0000
1:230337284:TAAAT:T	acceptor_gain	1.0000
1:230350954:TCA:T	donor_loss	1.0000
1:230350955:CACCT:C	donor_loss	1.0000
1:230350956:A:AG	donor_loss	1.0000
1:230351097:C:CT	acceptor_gain	1.0000
1:230323621:CT:C	acceptor_loss	0.9900
1:230323622:T:G	acceptor_loss	0.9900
1:230325312:G:A	donor_gain	0.9900
1:230325330:T:C	donor_gain	0.9900
1:230325412:ACTCC:A	acceptor_loss	0.9900
1:230325416:C:CA	acceptor_loss	0.9900
1:230325417:T:C	acceptor_loss	0.9900
1:230332836:GCAC:G	donor_loss	0.9900
1:230332837:CACT:C	donor_loss	0.9900
1:230332838:ACTC:A	donor_loss	0.9900
1:230332839:CT:C	donor_loss	0.9900
1:230332840:TCA:T	donor_loss	0.9900
1:230332841:CA:C	donor_loss	0.9900
1:230332842:A:AC	donor_gain	0.9900
1:230332843:C:CC	donor_gain	0.9900

AlphaMissense

3463 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:230323589:A:G	W471R	1.000
1:230323589:A:T	W471R	1.000
1:230357007:G:C	H216D	1.000
1:230323544:C:G	A486P	0.999
1:230323545:A:C	N485K	0.999
1:230323545:A:T	N485K	0.999
1:230323560:G:C	S480R	0.999
1:230323560:G:T	S480R	0.999
1:230323562:T:G	S480R	0.999
1:230323587:C:A	W471C	0.999
1:230323587:C:G	W471C	0.999
1:230323593:C:A	K469N	0.999
1:230323593:C:G	K469N	0.999
1:230356960:C:A	K231N	0.999
1:230356960:C:G	K231N	0.999
1:230357178:A:G	W159R	0.999
1:230357178:A:T	W159R	0.999
1:230357216:G:T	A146D	0.999
1:230323459:A:G	L514P	0.998
1:230323471:A:G	L510P	0.998
1:230323483:A:G	F506S	0.998
1:230323548:G:C	N484K	0.998
1:230323548:G:T	N484K	0.998
1:230323574:A:G	W476R	0.998
1:230323574:A:T	W476R	0.998
1:230323595:T:C	K469E	0.998
1:230350971:C:T	G294D	0.998
1:230351003:G:C	F283L	0.998
1:230351003:G:T	F283L	0.998
1:230351005:A:G	F283L	0.998

dbSNP variants (sampled 300 via entrez): RS1000001701 (1:230427541 C>A), RS1000084872 (1:230341734 A>G), RS1000098653 (1:230422523 A>C), RS1000113451 (1:230391167 G>A), RS1000144513 (1:230390990 T>C), RS1000145351 (1:230348103 C>A), RS1000159817 (1:230318600 C>T), RS1000167258 (1:230357644 C>G,T), RS1000179218 (1:230393935 G>A), RS1000234500 (1:230388415 ATTTTTTT>A,ATTT,ATTTT,ATTTTT,ATTTTTT,ATTTTTTTT,ATTTTTTTTT,ATTTTTTTTTT), RS1000251420 (1:230397637 T>A,C), RS1000279178 (1:230352544 C>G,T), RS1000294068 (1:230383468 G>A), RS1000338455 (1:230385516 G>A), RS1000362039 (1:230369873 G>A)

Disease associations

OMIM: gene MIM:616791 | disease phenotypes: MIM:621482

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder with seizures, hypotonia, and variable spasticity (MONDO:0980968)

Orphanet (0):

HPO phenotypes

38 total (30 of 38 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000331	Short chin
HP:0000473	Torticollis
HP:0000506	Telecanthus
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001265	Hyporeflexia
HP:0001272	Cerebellar atrophy
HP:0001332	Dystonia
HP:0001347	Hyperreflexia
HP:0002002	Deep philtrum
HP:0002061	Lower limb spasticity
HP:0002069	Bilateral tonic-clonic seizure
HP:0002169	Clonus
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0002376	Developmental regression
HP:0002509	Limb hypertonia
HP:0002714	Downturned corners of mouth
HP:0003487	Babinski sign
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0006986	Upper limb spasticity
HP:0007359	Focal-onset seizure
HP:0008936	Axial hypotonia
HP:0009748	Large earlobe
HP:0010864	Severe intellectual disability
HP:0011344	Severe global developmental delay

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003225_32	Pelvic organ prolapse (moderate/severe)	9.000000e-07
GCST006220_2	Basal ganglia growth	9.000000e-06
GCST008359_10	Response to cognitive-behavioural therapy in anxiety disorder	8.000000e-06
GCST009441_16	Age-related cognitive decline (memory) (slope of z-scores)	5.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy
EFO:0007710	cognitive decline measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects expression	5
Estradiol	affects cotreatment, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Tretinoin	decreases expression	2
sotorasib	affects cotreatment, increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	increases expression	1
3,4-dichloroaniline	increases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
bisphenol S	increases methylation	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Cadmium	increases abundance, decreases expression	1
Calcitriol	increases expression	1
Diuron	increases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Progesterone	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.