GeneBe

HECW2

HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2, the group of HECT domain containing|C2 domain containing

Basic information

Region (hg38): 2:196189099-196593684

Links

ENSG00000138411 ∙ NCBI:57520 ∙ OMIM:617245 ∙ HGNC:29853 ∙ Uniprot:Q9P2P5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • neurodevelopmental disorder with hypotonia, seizures, and absent language (Definitive), mode of inheritance: AD
  • neurodevelopmental disorder with hypotonia, seizures, and absent language (Strong), mode of inheritance: AD
  • neurodevelopmental disorder with hypotonia, seizures, and absent language (Strong), mode of inheritance: AD
  • complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
  • complex neurodevelopmental disorder (Limited), mode of inheritance: AR
  • neurodevelopmental disorder with hypotonia, seizures, and absent language (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Neurodevelopmental disorder with hypotonia, seizures, and absent languageADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Neurologic27334371; 27389779

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HECW2 gene.

  • not_provided (228 variants)
  • Inborn_genetic_diseases (172 variants)
  • Neurodevelopmental_disorder_with_hypotonia,_seizures,_and_absent_language (112 variants)
  • HECW2-related_disorder (45 variants)
  • not_specified (28 variants)
  • See_cases (6 variants)
  • Intellectual_disability (5 variants)
  • Oromandibular-limb_hypogenesis_spectrum (3 variants)
  • Neurofibromatosis,_type_1 (1 variants)
  • Complex_neurodevelopmental_disorder (1 variants)
  • Neurodevelopmental_disorder_with_hypotonia (1 variants)
  • Neurodevelopmental_disorder_with_progressive_microcephaly,_spasticity,_and_brain_anomalies (1 variants)
  • Abnormality_of_the_nervous_system (1 variants)
  • Neurodevelopmental_abnormality (1 variants)
  • HECW2-related_neurodevelopmental_disorder (1 variants)
  • Developmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HECW2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001348768.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
5
clinvar
52
clinvar
10
clinvar
 67
missense
6
clinvar
29
clinvar
258
clinvar
76
clinvar
8
clinvar
 377
nonsense
1
clinvar
8
clinvar
 9
start loss
0
frameshift
1
clinvar
6
clinvar
 7
splice donor/acceptor (+/-2bp)
4
clinvar
 4
Total 8 29 281 128 18

Highest pathogenic variant AF is 0.0000139545

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
HECW2protein_codingprotein_codingENST00000260983 28399323
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.000.0002991257260221257480.0000875
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense3.316259050.6910.000052310311
Missense in Polyphen149346.650.429833824
Synonymous0.7773233410.9470.00002023074
Loss of Function6.981380.60.1610.00000475865

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001740.000174
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.0001060.000105
Middle Eastern0.000.00
South Asian0.0001430.000131
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of TP73. Acts to stabilize TP73 and enhance activation of transcription by TP73 (PubMed:12890487). Involved in the regulation of mitotic metaphase/anaphase transition (PubMed:24163370). {ECO:0000269|PubMed:12890487, ECO:0000269|PubMed:24163370}.;
Disease
DISEASE: Neurodevelopmental disorder with hypotonia, seizures, and absent language (NDHSAL) [MIM:617268]: A neurodevelopmental disorder characterized by severely delayed psychomotor development, absent speech, epilepsy, encephalopathy, hypotonia, dystonia/dyskinesia, and macrocephaly. Brain imaging show cerebral atrophy, enlarged ventricles, and white matter abnormalities. {ECO:0000269|PubMed:27389779}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

pRec
0.106

Intolerance Scores

loftool
rvis_EVS
-2.47
rvis_percentile_EVS
0.98

Haploinsufficiency Scores

pHI
0.461
hipred
Y
hipred_score
0.563
ghis
0.528

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.795

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Hecw2
Phenotype
mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);

Gene ontology

Biological process
protein polyubiquitination;ubiquitin-dependent protein catabolic process;protein ubiquitination;regulation of mitotic metaphase/anaphase transition;proteasome-mediated ubiquitin-dependent protein catabolic process;positive regulation of protein catabolic process;regulation of dendrite morphogenesis;negative regulation of sodium ion transmembrane transporter activity
Cellular component
cytoplasm;mitotic spindle
Molecular function
protein binding;ubiquitin protein ligase activity