PARP4

protein-coding

poly(ADP-ribose) polymerase family member 4, the group of Poly(ADP-ribose) polymerases

Gene summary

This gene encodes poly(ADP-ribosyl)transferase-like 1 protein, which is capable of catalyzing a poly(ADP-ribosyl)ation reaction. This protein has a catalytic domain which is homologous to that of poly (ADP-ribosyl) transferase, but lacks an N-terminal DNA binding domain which activates the C-terminal catalytic domain of poly (ADP-ribosyl) transferase. Since this protein is not capable of binding DNA directly, its transferase activity may be activated by other factors such as protein-protein interaction mediated by the extensive carboxyl terminus. [provided by RefSeq, Jul 2008]

Previous symbols:

ADPRTL1

MANE transcript

NM_006437.4

Inheritance

—

ClinVar variants

U:258B:23

Top phenotype

PARP4-related condition

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr13:24,420,931-24,512,778

External References & Databases

Ensembl (ENSG00000102699)

Transcript & Mutation Effects

hg38 • Region Span ~91.8 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 PARP4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 231

not providedTotal: 22

PARP4-related conditionTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006437.4. 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			9 clinvar	6 clinvar	2 clinvar	17
missense			239 clinvar	12 clinvar	3 clinvar	254
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	0	258	18	5	281

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006437.4	RefSeq	NP_006428.2	33	MANE Select
ENST00000381989.4	Ensembl	ENSP00000371419.3	33	MANE Select
ENST00000908086.1	Ensembl	ENSP00000578145.1	33	Standard
ENST00000908087.1	Ensembl	ENSP00000578146.1	32	Standard

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)
NAD+ biosynthetic pathways

Biological Process

DNA repair
cellular protein modification process
protein ADP-ribosylation
inflammatory response
cellular response to DNA damage stimulus

Molecular Function

DNA binding
NAD+ ADP-ribosyltransferase activity
protein binding
enzyme binding

Cellular Component

nucleus
cytoplasm
cytosol
spindle microtubule
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000381989
Coding exons: 33
Length: 91885
Individuals with no LoFs: 125394
Homozygous LoFs: 1
Heterozygous LoFs: 353
Defined: 125748
p: 0.00141

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.127	878	889	0.988	0.0000461	11318
Missense (PolyPhen)		170	218.59	0.7777		2928
Synonymous	-0.848	356	336	1.06	0.0000193	3258
Loss of Function	2.78	55	82.2	0.669	0.00000413	1016

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0031	0.0031	notable
Latino/Admixed American	0.00059	0.00055	rare
Ashkenazi Jewish	0.00014	0.000099	rare
East Asian	0.0025	0.0024	notable
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.0012	0.0011	notable
South Asian	0.0041	0.0033	notable
Other	0.00093	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.988
RVIS EVS: 4.63
RVIS percentile EVS: 99.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.400

Gene Damage Prediction

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