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Early onset or syndromic epilepsy

Gene: PARP6

Amber List (moderate evidence)

PARP6 (poly(ADP-ribose) polymerase family member 6)
EnsemblGeneIds (GRCh38): ENSG00000137817
EnsemblGeneIds (GRCh37): ENSG00000137817
PARP6 is in 2 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: New gene added by Zornitza Stark. At least 3 individuals with heterozygous PARP6 variants and a relevant phenotype have been reported (PMID: 34067418) - however, segregation analysis has only been complete for one of these cases. Furthermore, identification of two sibs with biallelic variants and unaffected parents who were heterozygous carriers arises possibility of incomplete penetrance or role of variants in other genes.

Overall there is not enough evidence to add this gene as diagnostic grade, so rating Amber with watchlist tag.
Created: 13 Sep 2021, 3:08 p.m. | Last Modified: 13 Sep 2021, 3:08 p.m.
Panel Version: 3.1263
Vermehren-Schmaedick et al., 2021 (PMID: 34067418) describe four unrelated individuals with heterozygous variants in this gene, but without complete segregation studies in at least two of these families. Seizures and mild to severe GDD since early infancy with speech delay and learning disabilities were noted in 3/4 individuals, of which two had ID. Notably, one patient had normal psychomotor development. Furthermore, two sibs with compound het variants inherited from unaffected parents were also identified displaying GDD, epilepsy and various anomalies on brain imaging. Studies in primary rat hippocampal neurons of two variants, both located in the catalytic domain of PARP6, demonstrated opposite effects on dendritic complexity - with one variant increasing and the other decreasing complexity compared to controls.

This gene-disease association is described in OMIM but is currently pending confirmation. PARP6 is not yet listed in G2P and no further reports linking variants in this gene with disease have been published to date.
Created: 13 Sep 2021, 2:39 p.m. | Last Modified: 13 Sep 2021, 2:39 p.m.
Panel Version: 3.1262


Zornitza Stark (Australian Genomics)

Green List (high evidence)

Four unrelated individuals reported with de novo variants in this gene and a neurodevelopmental phenotype. Supportive functional data. One pair of siblings with a homozygous missense: limited evidence for bi-allelic variants causing disease.
Sources: Literature
Created: 11 Jun 2021, 9:38 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Intellectual disability; Epilepsy; Microcephaly



Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
  • Literature
  • Expert Review Amber
  • Intellectual disability
  • Epilepsy
  • Microcephaly
Clinvar variants
Variants in PARP6
Panels with this gene

History Filter Activity

13 Sep 2021, Gel status: 2

Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes

Arina Puzriakova (Genomics England Curator)

gene: PARP6 was added gene: PARP6 was added to Genetic epilepsy syndromes. Sources: Expert Review Amber,Literature watchlist tags were added to gene: PARP6. Mode of inheritance for gene: PARP6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PARP6 were set to 34067418 Phenotypes for gene: PARP6 were set to Intellectual disability; Epilepsy; Microcephaly