PARP6

protein-coding

poly(ADP-ribose) polymerase family member 6, the group of Poly(ADP-ribose) polymerases

Gene summary

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]

MANE transcript

NM_001323532.2

Inheritance

ClinVar variants

U:62

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr15:72,241,181-72,272,999

External References & Databases

Ensembl (ENSG00000137817)

Transcript & Mutation Effects

hg38 • Region Span ~31.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PARP6 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 46

not providedTotal: 1

Neurodevelopmental disorderTotal: 1

PARP6-related conditionTotal: 1

PARP6-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001323532.2. 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			1 clinvar			1
missense			52 clinvar			52
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	62	0	0	62

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 114 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001323532.2	RefSeq	NP_001310461.1	22	MANE Select
ENST00000569795.6	Ensembl	ENSP00000456348.1	22	MANE Select
NM_001323515.2	RefSeq	NP_001310444.1	22	Standard
NM_001323516.2	RefSeq	NP_001310445.1	22	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein ADP-ribosylation
positive regulation of dendrite morphogenesis

Molecular Function

NAD+ ADP-ribosyltransferase activity

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000569795
Coding exons: 22
Length: 31819
Individuals with no LoFs: 124789
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 124793
p: 0.0000160

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.18	187	356	0.526	0.0000190	4155
Missense (PolyPhen)		35	133.16	0.26285		1556
Synonymous	0.874	117	130	0.902	0.00000676	1185
Loss of Function	5.55	3	41.7	0.0719	0.00000209	477

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0783

Intolerance Scores

LoFtool: 0.174
RVIS EVS: -0.51
RVIS percentile EVS: 21.41

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.00640

Gene Damage Prediction

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