PGBD5

protein-coding

piggyBac transposable element derived 5, the group of DNA transposon derived genes

Gene summary

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]

MANE transcript

NM_001258311.2

Inheritance

—

ClinVar variants

P:4U:3B:6

Top phenotype

Neurodevelopmental disorder with seizures, hypotonia, and variable spasticity

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr1:230,314,490-230,426,332

External References & Databases

Ensembl (ENSG00000177614)

Transcript & Mutation Effects

hg38 • Region Span ~111.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PGBD5 variants in ClinVar

2 Conditions Cataloged

not providedTotal: 6

Neurodevelopmental disorder with seizures, hypotonia, and variable spasticityTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001258311.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar	2 clinvar	4
missense			3 clinvar		2 clinvar	5
nonsense	2 clinvar					2
start loss						0
frameshift	2 clinvar					2
splice donor/acceptor (+/-2bp)						0
Total	4	0	3	2	4	13

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001258311.2	RefSeq	NP_001245240.1	7	MANE Select
ENST00000391860.7	Ensembl	ENSP00000375733.2	7	MANE Select
ENST00000525115.1	Ensembl	ENSP00000431404.1	7	Standard
ENST00000525115.2	Ensembl	ENSP00000431404.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pathways in clear cell renal cell carcinoma

Biological Process

nucleic acid phosphodiester bond hydrolysis
non-replicative transposition, DNA-mediated

Molecular Function

endonuclease activity
transposase activity

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000525115
Coding exons: 7
Length: 104084
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125748
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.35	225	290	0.776	0.0000190	2999
Missense (PolyPhen)		67	101.41	0.66071		1114
Synonymous	-0.550	136	128	1.06	0.00000950	874
Loss of Function	2.54	8	20.4	0.393	0.00000109	220

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transposase that mediates sequence-specific genomic rearrangements (PubMed:26406119, PubMed:28504702). Can induce genomic rearrangements that inactivate the HPRT1 gene (PubMed:27491780). {ECO:0000269|PubMed:26406119, ECO:0000269|PubMed:27491780, ECO:0000269|PubMed:28504702}.;
Disease: DISEASE: Note=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. {ECO:0000269|PubMed:28504702}.;

Essentials

Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.186

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium