PARP6

Chr 15

poly(ADP-ribose) polymerase family member 6

Also known as: ARTD17, PARP-6-B1, PARP-6-C, pART17

NCBI Gene: 56965 ENSG00000137817 UniProt: Q2NL67

Enables NAD+-protein-aspartate ADP-ribosyltransferase activity and NAD+-protein-cysteine ADP-ribosyltransferase activity. Involved in protein auto-ADP-ribosylation. Predicted to be active in endoplasmic reticulum tubular network; membrane; and nuclear envelope. [provided by Alliance of Genome Resources, Jun 2026]

Research

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

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P/LP missense

0.19

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.19LOEUF

pLI 1.000

Z-score 5.55

OE 0.07 (0.03–0.19)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.18Z-score

OE missense 0.53 (0.47–0.59)

187 obs / 355.5 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.07 (0.03–0.19)

0≤0.351.4

Missense OE?0.53 (0.47–0.59)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 3 / 41.7Missense obs/exp: 187 / 355.5Syn Z: 0.87

Background carrier burden — how many people carry a rare variant somewhere in PARP6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

549 rare PASS variants

Rare truncating (LoF)

1 in 8,500

59 rare PASS variants

Rare synonymous (reference)

1 in 220

261 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PARP6. 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 220	1 in 13,000
South Asian	~43k	1 in 130	1 in 6,900
Remaining (unassigned)	~30k	1 in 190	≈ 1 in 15,000
European (Finnish)	~27k	1 in 580	1 in 2,700
Admixed American	~22k	1 in 150	≈ 1 in 11,000
African / African American	~21k	1 in 190	1 in 2,400
East Asian	~20k	1 in 190	≈ 1 in 6,400
Ashkenazi Jewish	~13k	1 in 300	none seen
Middle Eastern	~2,884	1 in 290	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 18 of 22 coding exons well covered in gnomAD exomes; exons 17, 19, 20, 21 marginal. Genomes: all 22.? see exons ↓