PARP9

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

Basic information

Region (hg38): 3:122527924-122564577

Links

ENSG00000138496 ∙ NCBI:83666 ∙ OMIM:612065 ∙ HGNC:24118 ∙ Uniprot:Q8IXQ6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PARP9 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PARP9 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			47	3	2	52
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			4			4
Total	0	0	51	3	2

Variants in PARP9

This is a list of pathogenic ClinVar variants found in the PARP9 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-122528387-C-T		not specified	Likely benign (Jan 23, 2024)
3-122528437-T-G		not specified	Uncertain significance (Mar 24, 2023)
3-122528439-A-T		not specified	Uncertain significance (Mar 24, 2023)
3-122528440-T-C		not specified	Uncertain significance (Oct 25, 2023)
3-122528564-T-C		not specified	Likely benign (Dec 16, 2022)
3-122528572-G-A		not specified	Uncertain significance (Nov 07, 2022)
3-122528578-A-G		not specified	Uncertain significance (Aug 11, 2024)
3-122528590-A-G		not specified	Uncertain significance (Dec 16, 2023)
3-122528597-T-C		not specified	Uncertain significance (Feb 27, 2024)
3-122528602-G-A		not specified	Uncertain significance (Jan 24, 2024)
3-122528611-T-C		not specified	Uncertain significance (Jun 06, 2022)
3-122528656-A-G		not specified	Uncertain significance (Aug 12, 2021)
3-122536993-T-C			Benign (Dec 31, 2019)
3-122537022-A-T		not specified	Uncertain significance (Oct 06, 2021)
3-122537055-T-G		not specified	Uncertain significance (Feb 03, 2022)
3-122540480-C-T		not specified	Uncertain significance (Oct 19, 2024)
3-122540481-G-A		not specified	Uncertain significance (Mar 06, 2023)
3-122540492-C-A		not specified	Uncertain significance (Dec 07, 2023)
3-122540533-C-T		not specified	Uncertain significance (Aug 02, 2024)
3-122540541-C-G		not specified	Uncertain significance (Aug 20, 2024)
3-122540543-A-G		not specified	Uncertain significance (Dec 05, 2022)
3-122540558-T-A		not specified	Uncertain significance (Sep 26, 2023)
3-122540585-A-G			Uncertain significance (Aug 30, 2019)
3-122540614-A-C		not specified	Likely benign (Jan 03, 2022)
3-122540694-G-A		not specified	Uncertain significance (May 29, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PARP9	protein_coding	protein_coding	ENST00000360356	10	36654

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.00e-9	0.990	125728	0	18	125746	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.01	385	445	0.865	0.0000214	5663
Missense in Polyphen		52	81.364	0.63911		1071
Synonymous	1.16	142	161	0.884	0.00000812	1599
Loss of Function	2.41	19	34.2	0.555	0.00000154	434

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000704	0.0000703
Middle Eastern	0.000163	0.000163
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.0634
• hipred: N
• hipred_score: 0.145
• ghis: 0.478

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.438

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Parp9

Gene ontology

• 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;negative regulation of gene expression;cell migration;NAD biosynthesis via nicotinamide riboside salvage pathway;positive regulation of chromatin binding;positive regulation of tyrosine phosphorylation of STAT protein;negative regulation of catalytic activity;innate immune response;positive regulation of transcription, DNA-templated;defense response to virus;regulation of response to interferon-gamma;positive regulation of interferon-gamma-mediated signaling pathway;protein poly-ADP-ribosylation;positive regulation of protein localization to nucleus;positive regulation of double-strand break repair via nonhomologous end joining
• Cellular component: nucleus;nucleoplasm;cytoplasm;mitochondrion;cytosol;membrane;protein-containing complex;site of DNA damage
• Molecular function: transcription corepressor activity;NAD+ ADP-ribosyltransferase activity;enzyme inhibitor activity;protein binding;enzyme binding;histone binding;ubiquitin-like protein ligase binding;NAD+ binding;ADP-D-ribose binding;STAT family protein binding