GeneBe

PARP9

protein-coding

poly(ADP-ribose) polymerase family member 9, the group of Macro domain containing|Poly(ADP-ribose) polymerases

Gene summary

Enables several functions, including STAT family protein binding activity; pentosyltransferase activity; and transcription corepressor activity. Involved in several processes, including positive regulation of tyrosine phosphorylation of STAT protein; regulation of defense response; and regulation of gene expression. Located in cytosol; nucleoplasm; and site of DNA damage. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001146105.2

Inheritance

—

ClinVar variants

U:93B:13

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr3:122,527,924-122,564,577

External References & Databases

Ensembl (ENSG00000138496)NCBI Gene (83666)OMIM (612065)HGNC:24118GenCCUniProt (Q8IXQ6)AlphaFoldClinVar (PARP9)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~36.7 kb
Loading mutation effect viewer...

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 PARP9 variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 99
not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001146105.2. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
 1
missense
88
clinvar
11
clinvar
2
clinvar
 101
nonsense
1
clinvar
 1
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
3
clinvar
 3
Total0093112106
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 124 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001146105.2RefSeqNP_001139577.110MANE Select
ENST00000682323.1EnsemblENSP00000507390.110MANE Select
NM_001146102.2RefSeqNP_001139574.110Standard
NM_001146103.2RefSeqNP_001139575.110Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • negative regulation of transcription by RNA polymerase II
  • positive regulation of defense response to virus by host
  • double-strand break repair
  • protein ADP-ribosylation
  • posttranscriptional regulation of gene expression

Molecular Function

  • transcription corepressor activity
  • NAD+ ADP-ribosyltransferase activity
  • enzyme inhibitor activity
  • protein binding
  • enzyme binding

Cellular Component

  • nucleus
  • nucleoplasm
  • cytoplasm
  • mitochondrion
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000360356
Coding exons
10
Length
36654
Individuals with no LoFs
125728
Homozygous LoFs
0
Heterozygous LoFs
18
Defined
125746
p
0.0000716
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.013854450.8650.00002145663
Missense (PolyPhen)5281.3640.639111071
Synonymous1.161421610.8840.000008121599
Loss of Function2.411934.20.5550.00000154434

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish00.0absent
East Asian0.000160.00016rare
Finnish00.0absent
European (Non-Finnish)0.0000700.000070rare
South Asian0.000130.00013rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: ADP-ribosyltransferase which, in association with E3 ligase DTX3L, plays a role in DNA damage repair and in immune responses including interferon-mediated antiviral defenses (PubMed:16809771, PubMed:23230272, PubMed:26479788, PubMed:27796300). Within the complex, enhances DTX3L E3 ligase activity which is further enhanced by PARP9 binding to poly(ADP- ribose) (PubMed:28525742). In association with DTX3L and in presence of E1 and E2 enzymes, mediates NAD(+)-dependent mono-ADP- ribosylation of ubiquitin which prevents ubiquitin conjugation to substrates such as histones (PubMed:28525742). During DNA repair, PARP1 recruits PARP9/BAL1-DTX3L complex to DNA damage sites via PARP9 binding to ribosylated PARP1 (PubMed:23230272). Subsequent PARP1-dependent PARP9/BAL1-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272, PubMed:28525742). In response to DNA damage, PARP9-DTX3L complex is required for efficient non-homologous end joining (NHEJ); the complex function is negatively modulated by PARP9 activity (PubMed:28525742). Dispensable for B-cell receptor (BCR) assembly through V(D)J recombination and class switch recombination (CSR) (By similarity). In macrophages, positively regulates pro-inflammatory cytokines production in response to IFNG stimulation by suppressing PARP14-mediated STAT1 ADP-ribosylation and thus promoting STAT1 phosphorylation (PubMed:27796300). Also suppresses PARP14-mediated STAT6 ADP-ribosylation (PubMed:27796300). {ECO:0000250|UniProtKB:Q8CAS9, ECO:0000269|PubMed:16809771, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:27796300, ECO:0000269|PubMed:28525742}.;
Disease
DISEASE: Note=Overexpressed at significantly higher levels in fatal high-risk diffuse large B-cell lymphomas (DLB-CL) compared to cured low-risk tumors. Overexpression in B-cell lymphoma transfectants may promote malignant B-cell migration. May therefore be involved in promoting B-cell migration and dissemination of high-risk DLB-CL tumors (PubMed:11110709). {ECO:0000269|PubMed:11110709}.;

Recessive Scores

pRec
0.0815

Intolerance Scores

LoFtool
0.947
RVIS EVS
-0.39
RVIS percentile EVS
27.03

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.438

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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