geno logo
     HELP     Sign In

Quick Links

TOOLS
Search

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
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
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
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
The contribution of de novo coding mutations to autism spectrum disorder
ASD
Support
ASD
DD, ID
Support
Mutation of HERC2 causes developmental delay with Angelman-like features.
DD, ID
Support
Integrating de novo and inherited variants in 42
ASD
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
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 
 GEN431R006 
 missense_variant 
 c.2236C>T 
 p.Arg746Cys 
 De novo 
  
 Simplex 
 GEN431R007a 
 copy_number_loss 
  
  
 Familial 
 Both parents 
 Simplex 
 GEN431R008a 
 splice_site_variant 
 c.4676-1G>A 
  
 Familial 
 Both parents 
  
 GEN431R009 
 missense_variant 
 c.9170G>A 
 p.Arg3057Gln 
 Unknown 
  
 Simplex 
 GEN431R010 
 synonymous_variant 
 c.13026C>A 
 p.Pro4342= 
 De novo 
  
 Simplex 
 GEN431R011 
 missense_variant 
 c.6064C>T 
 p.Arg2022Trp 
 De novo 
  
 Simplex 
 GEN431R012 
 synonymous_variant 
 c.12234G>A 
 p.Pro4078= 
 De novo 
  
  
 GEN431R013 
 splice_site_variant 
 c.5464+5G>A 
  
 De novo 
  
  
 GEN431R014 
 missense_variant 
 c.11636T>C 
 p.Met3879Thr 
 De novo 
  
  
 GEN431R015 
 synonymous_variant 
 c.9486C>T 
 p.Asp3162= 
 De novo 
  
  
 GEN431R016 
 frameshift_variant 
 c.9364_9370del 
 p.Thr3122AlafsTer17 
 De novo 
  
  
 GEN431R017 
 splice_region_variant 
 c.3050+7C>T 
  
 De novo 
  
  
 GEN431R018a 
 missense_variant 
 c.3203G>A 
 p.Gly1068Glu 
 Familial 
 Maternal 
 Simplex 
 GEN431R018b 
 missense_variant 
 c.6514C>T 
 p.Arg2172Cys 
 Familial 
 Paternal 
 Simplex 
 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) 
 GEN431R020 
 missense_variant 
 c.11243G>A 
 p.Ser3748Asn 
 De novo 
  
  
 GEN431R021 
 missense_variant 
 c.7691C>G 
 p.Ala2564Gly 
 Unknown 
  
  
 GEN431R022 
 missense_variant 
 c.13612G>A 
 p.Val4538Met 
 Unknown 
  
  
 GEN431R023a 
 missense_variant 
 c.11669G>T 
 p.Arg3890Ile 
 Familial 
 Paternal 
  
 GEN431R023b 
 missense_variant 
 c.1150G>A 
 p.Glu384Lys 
 Unknown 
  
  

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
15
Duplication
 10
  construct
15
Duplication
 1
 
15
Duplication
 4
 
15
Duplication
 9
 
15
Duplication
 3
 
15
Duplication
 5
 
15
Deletion
 1
 
15
Deletion-Duplication
 124
 
15
Duplication
 10
 
15
Duplication
 89
  construct
15
Duplication
 10
 
15
Duplication
 21
 
15
Duplication
 3
 
15
Deletion-Duplication
 12
 
15
Duplication
 5
 
15
Deletion-Duplication
 14
 
15
Deletion
 21
 

No Animal Model Data Available





Download HERC2's Cytoscape file

Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
APBA2 amyloid beta (A4) precursor protein-binding, family A, member 2 321 Q59G28 IP; LC-MS/MS
Huttlin EL , et al. 2015
APBB1 Amyloid beta A4 precursor protein-binding family B member 1 322 O00213 IP; LC-MS/MS
Huttlin EL , et al. 2015
ARID3A AT rich interactive domain 3A (BRIGHT-like) 1820 Q99856 IP; LC-MS/MS
Huttlin EL , et al. 2015
ATRIP ATR interacting protein 84126 B4DU92 IP/WB
Izawa N , et al. 2011
BIRC6 baculoviral IAP repeat containing 6 57448 Q9NR09 IP; LC-MS/MS
Huttlin EL , et al. 2015
BRCA1 breast cancer 1, early onset 672 P38398 IP/WB
Wu W , et al. 2010
C16ORF88 chromosome 16 open reading frame 88 400506 Q1ED39 IP; LC-MS/MS
Huttlin EL , et al. 2015
CALM1 calmodulin 1 (phosphorylase kinase, delta) 801 P62158 IP/WB
Shen X , et al. 2005
CCDC111 DNA-directed primase/polymerase protein 201973 Q96LW4 IP; LC-MS/MS
Huttlin EL , et al. 2015
CCDC136 coiled-coil domain containing 136 64753 Q96JN2 IP; LC-MS/MS
Huttlin EL , et al. 2015
CCDC65 Coiled-coil domain-containing protein 65 85478 Q8IXS2-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
CCDC88A coiled-coil domain containing 88A 55704 Q3V6T2 IP; LC-MS/MS
Huttlin EL , et al. 2015
CCP110 centriolar coiled coil protein 110kDa 9738 B4DTZ1 MS/MS
Al-Hakim AK , et al. 2012
CDC42 cell division cycle 42 (GTP binding protein, 25kDa) 998 P60953 Y2H
Bandyopadhyay S , et al. 2010
CEP170 centrosomal protein 170kDa 9859 Q5SW79 LAP-MS
Hutchins JR , et al. 2010
CLSPN claspin 63967 Q9HAW4 IP/WB
Izawa N , et al. 2011
DBNL drebrin-like 28988 Q9UJU6 LC/ESI/MS/MS
Ewing RM , et al. 2007
DBNL drebrin-like 28988 Q9UJU6 IP; LC-MS/MS
Huttlin EL , et al. 2015
DNAJA1 DnaJ (Hsp40) homolog, subfamily A, member 1 3301 P31689 IP; LC-MS/MS
Huttlin EL , et al. 2015
DNAJB5 DnaJ homolog subfamily B member 5 25822 O75953 IP; LC-MS/MS
Huttlin EL , et al. 2015
ECI2 enoyl-CoA delta isomerase 2 10455 O75521 MS/MS
Al-Hakim AK , et al. 2012
FAM98A family with sequence similarity 98, member A 25940 I6L9E8 IP; LC-MS/MS
Huttlin EL , et al. 2015
FARP2 FERM, RhoGEF and pleckstrin domain protein 2 9855 O94887 IP; LC-MS/MS
Huttlin EL , et al. 2015
FBXL5 F-box and leucine-rich repeat protein 5 26234 Q9UKA1 IP; LC-MS/MS
Huttlin EL , et al. 2015
gag-pol Gag-Pol polyprotein 155348 P04585 MS
Jger S , et al. 2011
HERC2 HECT and RLD domain containing E3 ubiquitin protein ligase 2 8924 A8KAQ8 MS/MS
Al-Hakim AK , et al. 2012
HOOK1 hook homolog 1 (Drosophila) 51361 Q9UJC3 IP; LC-MS/MS
Huttlin EL , et al. 2015
HSDL2 hydroxysteroid dehydrogenase like 2 84263 Q6YN16 IP; LC-MS/MS
Huttlin EL , et al. 2015
KTN1 kinectin 1 (kinesin receptor) 3895 Q5GGW3 MS/MS
Al-Hakim AK , et al. 2012
LGALS3BP lectin, galactoside-binding, soluble, 3 binding protein 3959 Q08380 IP; LC-MS/MS
Huttlin EL , et al. 2015
LRRK2 leucine-rich repeat kinase 2 120892 Q5S007 IP; LC-MS/MS; IP/WB
Imai Y , et al. 2015
MAP7D2 MAP7 domain containing 2 256714 Q96T17 IP; LC-MS/MS
Huttlin EL , et al. 2015
MAPK6 mitogen-activated protein kinase 6 5597 Q16659 IP; LC-MS/MS
Huttlin EL , et al. 2015
MDC1 mediator of DNA-damage checkpoint 1 9656 A1Z5I9 Affinity Capture-Western
Bekker-Jensen S , et al. 2009
MPDU1 mannose-P-dolichol utilization defect 1 9526 O75352 LC/ESI/MS/MS
Ewing RM , et al. 2007
NCOA4 nuclear receptor coactivator 4 8031 E9PAV7 IP; LC-MS/MS
Huttlin EL , et al. 2015
NEURL4 neuralized homolog 4 (Drosophila) 84461 Q96JN8 MS/MS
Al-Hakim AK , et al. 2012
PHKG2 phosphorylase kinase, gamma 2 (testis) 5261 P15735 LC-MS/MS
Varjosalo M , et al. 2013
PIAS4 protein inhibitor of activated STAT, 4 51588 Q8N2W9 IP/WB
Danielsen JR , et al. 2012
PMS1 PMS1 postmeiotic segregation increased 1 (S. cerevisiae) 5378 P54277 IP; MS
Cannavo E , et al. 2006
RABEP1 rabaptin, RAB GTPase binding effector protein 1 9135 Q15276 IP; LC-MS/MS
Huttlin EL , et al. 2015
RNF11 ring finger protein 11 26994 Q9Y3C5 Y2H
Colland F , et al. 2004
RNF115 E3 ubiquitin-protein ligase RNF115 27246 Q9Y4L5 IP; LC-MS/MS
Huttlin EL , et al. 2015
RNF166 RING finger protein 166 115992 Q96A37 IP; LC-MS/MS
Huttlin EL , et al. 2015
RNF168 ring finger protein 168, E3 ubiquitin protein ligase 165918 Q8IYW5 IP/WB
Bekker-Jensen S , et al. 2009
RNF8 ring finger protein 8, E3 ubiquitin protein ligase 9025 O76064 IP/WB
Danielsen JR , et al. 2012
RPA1 replication protein A1, 70kDa 6117 P27694 MS/MS
Al-Hakim AK , et al. 2012
RPA3 replication protein A3, 14kDa 6119 A4D105 MS/MS
Al-Hakim AK , et al. 2012
SEC23IP SEC23 interacting protein 11196 Q9Y6Y8 MS/MS
Al-Hakim AK , et al. 2012
SIRT3 sirtuin 3 23410 Q9NTG7 LC MALDI-TOF/TOF MS/MS
Law IK , et al. 2009
SIRT7 sirtuin 7 51547 Q9NRC8 LC-MS/MS
Tsai YC , et al. 2012
SOST Sclerostin 50964 Q9BQB4 IP; LC-MS/MS
Huttlin EL , et al. 2015
SPZ1 Spermatogenic leucine zipper protein 1 84654 Q9BXG8 IP; LC-MS/MS
Huttlin EL , et al. 2015
SRGAP2 SLIT-ROBO Rho GTPase activating protein 2 23380 O75044 MS/MS
Al-Hakim AK , et al. 2012
SSSCA1 Sjogren syndrome/scleroderma autoantigen 1 10534 O60232 MS/MS
Al-Hakim AK , et al. 2012
SSSCA1 Sjogren syndrome/scleroderma autoantigen 1 10534 O60232 IP; LC-MS/MS
Huttlin EL , et al. 2015
STK33 serine/threonine kinase 33 65975 Q9BYT3 LC-MS/MS
Azoitei N , et al. 2012
SUMO1 SMT3 suppressor of mif two 3 homolog 1 (S. cerevisiae) 7341 P63165 IP/WB
Danielsen JR , et al. 2012
TANK TRAF family member-associated NFKB activator 10010 Q92844 MS/MS
Al-Hakim AK , et al. 2012
TBK1 TANK-binding kinase 1 29110 Q9UHD2 MS/MS
Al-Hakim AK , et al. 2012
TOP3B topoisomerase (DNA) III beta 8940 O95985 HITS-CLIP
Xu D , et al. 2013
UBC ubiquitin C 7316 P63279 LC-MS/MS
Danielsen JM , et al. 2010
UBE2N ubiquitin-conjugating enzyme E2N 7334 P61088 Affinity Capture-Western
Bekker-Jensen S , et al. 2009
UBE3A ubiquitin protein ligase E3A 7337 Q05086 IP; MS; COMPASS; IP/WB
Martnez-Nol G , et al. 2012
USP16 ubiquitin specific peptidase 16 10600 Q9Y5T5 LC-MS/MS
Sowa ME , et al. 2009
USP16 ubiquitin specific peptidase 16 10600 Q9Y5T5 IP; LC-MS/MS
Huttlin EL , et al. 2015
USP19 ubiquitin specific peptidase 19 10869 O94966 LC-MS/MS
Sowa ME , et al. 2009
USP20 ubiquitin specific peptidase 20 10868 Q9Y2K6 LC-MS/MS
Sowa ME , et al. 2009
USP42 ubiquitin specific peptidase 42 84132 Q9H9J4 LC-MS/MS
Sowa ME , et al. 2009
XPA xeroderma pigmentosum, complementation group A 7507 P23025 IP/WB
Lee TH , et al. 2012
ZNF286A zinc finger protein 286A 57335 B2RCD9 IP; LC-MS/MS
Huttlin EL , et al. 2015
ZRANB1 zinc finger, RAN-binding domain containing 1 54764 Q9UGI0 LC-MS/MS
Sowa ME , et al. 2009
FMR1 fragile X mental retardation 1 14265 P35922 HITS-CLIP
Darnell JC , et al. 2011

HELP
Copyright © 2017 MindSpec, Inc.