HERC2
Homo sapiens
Gene Name: HECT and RLD domain containing E3 ubiquitin protein ligase 2
Aliases: D15F37S1, SHEP1, jdf2, p528
Chromosome No: 15
Chromosome Band: 15q13.1
Genetic Category: Rare single gene variant-Syndromic--Multigenic CNV-Functional-Syndromic/Functional
Associated Syndrome(s): Autosomal recessive mental retardation-38
Aliases: D15F37S1, SHEP1, jdf2, p528
Chromosome No: 15
Chromosome Band: 15q13.1
Genetic Category: Rare single gene variant-Syndromic--Multigenic CNV-Functional-Syndromic/Functional
Associated Syndrome(s): Autosomal recessive mental retardation-38
Summary Statistics:
ASD Reports: 19
Recent Reports: 1
Annotated variants: 32
Associated CNVs: 17
Evidence score: 3
ASD Reports: 19
Recent Reports: 1
Annotated variants: 32
Associated CNVs: 17
Evidence score: 3
| Associated Disorders: |
|
Relevance to Autism
Genome-wide mapping and exome sequencing of seven affected children in three separate sibships from the Mennonite (Plain) community identified a homozygous missense variant in the HERC2 gene (c.1781C>T; p.Pro594Leu) in all seven affected children, who presented with global developmental delay/mental retardation, autistic behavior, and gait instability (Puffenberger et al., 2012). No homozygotes or heterozygotes for this variant were found in 380 control samples from the Lancaster Amish and Lancaster Mennonite community.
Molecular Function
E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. Genetic variants in HERC2 define the skin/hair/eye pigmentation variation locus 1 (SHEP1) [MIM:227220].
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
A homozygous missense mutation in HERC2 associated with global developmental delay and autism spectrum disorder.
DD, ID
ASD
Support
Mutation of HERC2 causes developmental delay with Angelman-like features.
DD, ID
Support
Genetic Traces in Autism Spectrum Disorders: A Whole Exome Sequencing Study from Türkiye
ASD
Epilepsy/seizures
Support
Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort.
ASD
Support
Rare Variant Burden and Behavioral Phenotypes in Children with Autism in Slovakia
ASD
Support
Proteomic investigations of human HERC2 mutants: Insights into the pathobiology of a neurodevelopmental disorder.
Support
Whole genome sequencing analysis identifies sex differences of familial pattern contributing to phenotypic diversity in autism
ASD
Support
Genomic landscape of rare variants in a Chinese autism cohort and discovery of novel risk genes.
ASD
Support
Clinical exome sequencing: results from 2819 samples reflecting 1000 families.
Autosomal recessive mental retardation-38
DD, epilepsy/seizures, hypotonia
Support
Rare Pathogenic Variants Identified in Whole Exome Sequencing of Monozygotic Twins With Autism Spectrum Disorder
ASD
Support
Genetic insights into autism spectrum disorder with intellectual disability: a regional population-based study from Northwest China.
ASD, ID
Support
Complete loss of function of the ubiquitin ligase HERC2 causes a severe neurodevelopmental phenotype.
Structural brain abnormalities, hypotonia
Support
Autophagy dysregulation via the USP20-ULK1 axis in the HERC2-related neurodevelopmental disorder
Autosomal recessive intellectual developmental dis
Support
Genetic variants identification through whole-genome sequencing based on dried blood spots in 92 Chinese children with Autism.
ASD
Support
The contribution of de novo coding mutations to autism spectrum disorder
ASD
Support
Proteasome dysfunction underlies HERC2-linked neurodevelopmental disorder with Angelman-like clinical features.
Autosomal recessive intellectual developmental dis
Recent Recommendation
Low load for disruptive mutations in autism genes and their biased transmission.
ASD
Rare
Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
GEN431R001a
missense_variant
c.1781C>T
p.Pro594Leu
Familial
Both parents
Multiplex
GEN431R002a
missense_variant
c.1781C>T
p.Pro594Leu
Familial
Both parents
Multiplex
GEN431R003a
missense_variant
c.1781C>T
p.Pro594Leu
Familial
Both parents
Multiplex
GEN431R004a
missense_variant
c.1781C>T
p.Pro594Leu
Familial
Both parents
Multi-generational
GEN431R005a
missense_variant
c.1781C>T
p.Pro594Leu
Familial
Both parents
Multiplex
GEN431R019a
missense_variant
c.905C>T
p.Thr302Met
De novo
Multiplex (monozygotic twins)
GEN431R019b
missense_variant
c.839G>T
p.Ser280Ile
De novo
Multiplex (monozygotic twins)
GEN431R019c
frameshift_variant
c.836del
p.Gly279GlufsTer25
De novo
Multiplex (monozygotic twins)
Common
No Common Variants Available
