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Intellectual disability

Gene: HERC2

Red List (low evidence)

HERC2 (HECT and RLD domain containing E3 ubiquitin protein ligase 2)
EnsemblGeneIds (GRCh38): ENSG00000128731
EnsemblGeneIds (GRCh37): ENSG00000128731
OMIM: 605837, Gene2Phenotype
HERC2 is in 1 panel

2 reviews

Konstantinos Varvagiannis (Other)

I don't know

PMID 23065719 describes 7 affected individuals from 3 sibships (from the Amish or Mennonite populations) homozygous for a missense variant (c.1781C>T/p.Pro594Leu). All individuals presented with DD/ID, autistic behavior and gait instability. Functional studies demonstrated decreased HERC2 abundance.

In PMID 23243086, 15 subjects from 2 large Amish families are reported, with similar phenotype including hypotonia, DD/ID, unstable gait with broad base and arms held upward and seizures in a few individuals. All the patients were homozygous for the same missense variant reported in 23065719. Levels of HERC2 were shown to be diminished in fibroblasts from affected individuals.

Given some phenotypic similarities with AS, both studies excluded methylation abnormalities at the SNRPN locus (as well as UBE3A pathogenic variants in 23065719).
Created: 12 Aug 2018, 8:51 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mental retardation, autosomal recessive 38, 615516

Publications

Zornitza Stark (Australian Genomics)

I don't know

Three sibships with bi-allelic variants reported in this gene; however likely founder effect. Suggest inclusion as Amber or Red.
Created: 22 Jun 2018, 11:19 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mental retardation, autosomal recessive 38

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
Phenotypes
  • Mental retardation, autosomal recessive 38
OMIM
605837
Clinvar variants
Variants in HERC2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

28 Sep 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to HERC2.

22 Jun 2018, Gel status: 0

Added New Source

Zornitza Stark (Australian Genomics)

HERC2 was added to Intellectual disability panel. Sources: Literature

22 Jun 2018, Gel status: 0

Created

Zornitza Stark (Australian Genomics)

HERC2 was created by Zornitza Stark