PARP14

protein-coding

poly(ADP-ribose) polymerase family member 14, the group of Macro domain containing|Poly(ADP-ribose) polymerases

Gene summary

This gene encodes a member of the poly(ADP-ribose) polymerase (PARP) protein family. The encoded anti-apoptotic protein may regulate aerobic glycolysis and promote survival of cancer cells. Increased expression of this gene has been reported in a variety of tumor types. [provided by RefSeq, Jul 2016]

MANE transcript

NM_017554.3

Inheritance

—

ClinVar variants

U:187B:30

Top phenotype

Abnormality of neuronal migration

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr3:122,680,839-122,730,840

External References & Databases

Ensembl (ENSG00000173193)

Transcript & Mutation Effects

hg38 • Region Span ~50.0 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 PARP14 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 192

not providedTotal: 5

Abnormality of neuronal migrationTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017554.3. 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		1 clinvar	3
missense			179 clinvar	24 clinvar	5 clinvar	208
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	187	24	6	217

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017554.3	RefSeq	NP_060024.2	17	MANE Select
ENST00000474629.7	Ensembl	ENSP00000418194.2	17	MANE Select
ENST00000460683.1	Ensembl	ENSP00000420649.1	12	Standard
ENST00000494811.2	Ensembl	ENSP00000418535.2	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

IL4-mediated signaling events

Biological Process

protein ADP-ribosylation
negative regulation of gene expression
positive regulation of tyrosine phosphorylation of STAT protein
negative regulation of tyrosine phosphorylation of STAT protein
innate immune response

Molecular Function

NAD+ ADP-ribosyltransferase activity
protein binding
enzyme binding

Cellular Component

nucleus
cytoplasm
cytosol
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000474629
Coding exons: 17
Length: 50223
Individuals with no LoFs: 124623
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 124651
p: 0.000112

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.63	698	922	0.757	0.0000466	11864
Missense (PolyPhen)		133	251.5	0.52882		3374
Synonymous	0.663	339	355	0.955	0.0000189	3389
Loss of Function	5.59	18	67.6	0.266	0.00000325	949

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00014	0.00013	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.000069	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: ADP-ribosyltransferase (PubMed:16061477, PubMed:27796300). By mono-ADP-ribosylating STAT1 at 'Glu-657' and 'Glu-705' and thus decreasing STAT1 phosphorylation, negatively regulates pro-inflammatory cytokines production in macrophages in response to IFNG stimulation (PubMed:27796300). Mono-ADP- ribosylates STAT6 (By similarity). Enhances STAT6-dependent transcription (By similarity). In macrophages, positively regulates MRC1 expression in response to IL4 stimulation by promoting STAT6 phosphorylation (PubMed:27796300). Mono-ADP- ribosylates PARP9 (PubMed:27796300). {ECO:0000250|UniProtKB:Q2EMV9, ECO:0000269|PubMed:16061477, ECO:0000269|PubMed:27796300}.;

Recessive Scores

pRec: 0.0851

Intolerance Scores

LoFtool: 0.658
RVIS EVS: -0.55
RVIS percentile EVS: 20.02

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.590

Gene Damage Prediction

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