Developmental Brain Disorder Gene Database

LoF Variant Gene

Gene

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AR

HECTD4

HGNC:26611 (protein-coding gene)

HECT domain E3 ubiquitin protein ligase 4

Unique Cases:: 4

Disorders:: ID, ASD, EP

Last Updated:: November 4, 2024

Gene Summary:

DBD Genes Classification: HECTD4 is a High Confidence candidate gene classified as Tier AR. AR genes have autosomal recessive inheritance.

Gene Function: E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. {ECO:0000250}. (Source: Uniprot)

Previous symbols: C12orf51

Alias symbols: FLJ34154, KIAA0614

Chromosomal Location: 12q24.13

Genomic Coordinates: GRCh37:chr12:112597992-112819896; GRCh38:chr12:112160195-112382431

Associated Disorders: Intellectual Disability, Autism, Epilepsy

Predictive Scores:

HI Score (Decipher): 23.9

pLI (gnomAD): 1.00

LOEUF (gnomAD): 0.29

Classifications from External Sources:

SFARI Score (SFARI): 1

DDG2P Classification (DDG2P): No Classification

ClinGen Classification (ClinGen): No Classification

GenCC Classification (GenCC): Limited1 Strong1 Moderate3

Cases:

Publications:

Coe BP et. al., Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity., Nat Genet, 2019

Faqeih EA et. al., Biallelic variants in HECT E3 paralogs, HECTD4 and UBE3C, encoding ubiquitin ligases cause neurodevelopmental disorders that overlap with Angelman syndrome., Genet Med, 2022

External References:

NCBI: Gene

Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.

NCBI: Gene

Gene Reviews

An international point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.

Gene Reviews

DECIPHER

DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient.

DECIPHER

SFARI

SFARI Gene is an evolving online database designed to permit quick entrée into the genetics of autism, and to help researchers track the ever-expanding genetic risk factors that emerge in the literature.

SFARI

ClinGen

ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.

ClinGen

GenCC

The GenCC DB provides information pertaining to the validity of gene-disease relationships, with a current focus on Mendelian diseases.

GenCC

gnomAD

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects, and making summary data available for the wider scientific community.