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…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.40

LOEUF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in PARP14?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 38

1,888 rare PASS variants

Rare truncating (LoF)

1 in 380

183 rare PASS variants

Rare synonymous (reference)

1 in 66

777 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PARP14. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 43	1 in 440
South Asian	~43k	1 in 39	1 in 430
Remaining (unassigned)	~30k	1 in 37	1 in 380
European (Finnish)	~27k	1 in 120	1 in 720
Admixed American	~22k	1 in 37	1 in 2,100
African / African American	~21k	1 in 40	1 in 460
East Asian	~20k	1 in 41	1 in 450
Ashkenazi Jewish	~13k	1 in 120	1 in 510
Middle Eastern	~2,884	1 in 36	1 in 300

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 14 of 17 coding exons well covered in gnomAD exomes; exons 3, 5, 9 marginal. Genomes: all 17.? see exons ↓