PARP14

Chr 3

poly(ADP-ribose) polymerase family member 14

Also known as: ARTD8, BAL2, PARP-14, pART8

NCBI Gene: 54625 ENSG00000173193 UniProt: Q460N5 OMIM: 610028

The protein is an ADP-ribosyltransferase that catalyzes mono-ADP-ribosylation of target proteins including STAT1 and STAT6, regulating inflammatory responses and macrophage function. PARP14 is highly constrained against loss-of-function variants (LOEUF 0.395), but no Mendelian diseases have been definitively associated with mutations in this gene to date. The gene's role in cellular signaling pathways suggests potential for neurodevelopmental phenotypes if pathogenic variants are identified.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.40

Clinical Summary— PARP14

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.

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ClinVar Variants

167 VUS of 229 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.40LOEUF

pLI 0.007

Z-score 5.59

OE 0.27 (0.18–0.40)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.63Z-score

OE missense 0.76 (0.71–0.81)

698 obs / 922.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.27 (0.18–0.40)

0≤0.351.4

Missense OE?0.76 (0.71–0.81)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 18 / 67.6Missense obs/exp: 698 / 922.4Syn Z: 0.66

This gene — mechanism propensity

0.6937th %ile

GOF

0.6053th %ile

LOF

0.2092th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

229 submitted variants in ClinVar

ClinVar

Classification Summary

VUS167

Likely Benign24

Benign6

167

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	167	0	167
Likely Benign	24	0	24
Benign	5	1	6
Total	196	1	197

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

17 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap PARP14 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →