PARP3
protein-codingpoly(ADP-ribose) polymerase family member 3, the group of Poly(ADP-ribose) polymerases
Gene summary
The protein encoded by this gene belongs to the PARP family. These enzymes modify nuclear proteins by poly-ADP-ribosylation, which is required for DNA repair, regulation of apoptosis, and maintenance of genomic stability. This gene encodes the poly(ADP-ribosyl)transferase 3, which is preferentially localized to the daughter centriole throughout the cell cycle. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
- ADPRTL3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.5 kbGenCC 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 PARP3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001003931.4. 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 | 1 | 3 | |||
| missense | 84 | 11 | 3 | 98 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 86 | 13 | 4 | 103 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001003931.4 | 10 | MANE Select | |
| Ensembl | ENSP00000381740.4 | 10 | MANE Select | |
| RefSeq | NP_001357168.1 | 10 | Standard | |
| RefSeq | NP_001357169.1 | 10 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| parp3 | Danio rerio | Structure: pectoral fin Quality: aplastic abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Base excision repair - Homo sapiens (human)
- Necroptosis - Homo sapiens (human)
- Apoptosis - Homo sapiens (human)
Biological Process
- telomere maintenance
- DNA repair
- double-strand break repair
- protein ADP-ribosylation
- positive regulation of DNA ligation
Molecular Function
- catalytic activity
- NAD+ ADP-ribosyltransferase activity
- protein ADP-ribosylase activity
Cellular Component
- nucleus
- nucleolus
- centriole
- site of double-strand break
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000398755
- Coding exons
- 11
- Length
- 6523
- Individuals with no LoFs
- 124383
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 427
- Defined
- 124812
- p
- 0.00172
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.310 | 301 | 317 | 0.951 | 0.0000184 | 3546 |
| Missense (PolyPhen) | 91 | 93.222 | 0.97617 | 1128 | ||
| Synonymous | 0.644 | 117 | 126 | 0.927 | 0.00000748 | 1022 |
| Loss of Function | 0.585 | 23 | 26.2 | 0.877 | 0.00000129 | 297 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0071 | 0.0071 | notable |
| Latino/Admixed American | 0.00064 | 0.00064 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00028 | 0.00028 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.0011 | 0.0011 | notable |
| South Asian | 0.0056 | 0.0055 | notable |
| Other | 0.00067 | 0.00066 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. May link the DNA damage surveillance network to the mitotic fidelity checkpoint. Negatively influences the G1/S cell cycle progression without interfering with centrosome duplication. Binds DNA. May be involved in the regulation of PRC2 and PRC3 complex-dependent gene silencing. {ECO:0000269|PubMed:16924674}.;
Recessive Scores
- pRec
- 0.0853
Intolerance Scores
- LoFtool
- 0.947
- RVIS EVS
- 0.8
- RVIS percentile EVS
- 87.69
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.124
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |