HECTD4

HECT domain E3 ubiquitin protein ligase 4, the group of MicroRNA protein coding host genes|HECT domain containing

Basic information

Region (hg38): 12:112160188-112382439

Previous symbols: [ "C12orf51" ]

Links

ENSG00000173064 ∙ NCBI:283450 ∙ OMIM:620209 ∙ HGNC:26611 ∙ Uniprot:Q9Y4D8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum (Limited), mode of inheritance: AR
• neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum (Strong), mode of inheritance: AR
• neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Dental; Neurologic	36401616

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HECTD4 gene.

• not_specified (373 variants)
• not_provided (36 variants)
• HECTD4-related_disorder (23 variants)
• Neurodevelopmental_disorder_with_seizures,_spasticity,_and_complete_or_partial_agenesis_of_the_corpus_callosum (13 variants)
• Autism_spectrum_disorder (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HECTD4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001388303.1. 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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				16	6	22
missense	2		386	13		401
nonsense	2	1				3
start loss						0
frameshift	1	2				3
splice donor/acceptor (+/-2bp)		1				1
Total	5	4	386	29	6

Highest pathogenic variant AF is 0.00000715383

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HECTD4	protein_coding	protein_coding	ENST00000550722	75	221905

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.66e-21	125530	0	63	125593	0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	6.94	1429	2.38e+3	0.600	0.000144	27641
Missense in Polyphen		414	847.44	0.48853		9521
Synonymous	1.43	933	990	0.942	0.0000657	8703
Loss of Function	12.0	17	201	0.0847	0.0000114	2327

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000494	0.000484
Ashkenazi Jewish	0.000202	0.000199
East Asian	0.000123	0.000109
Finnish	0.000325	0.000324
European (Non-Finnish)	0.000402	0.000344
Middle Eastern	0.000123	0.000109
South Asian	0.0000668	0.0000653
Other	0.000166	0.000163

dbNSFP

Source: dbNSFP

• Function: 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}.

Recessive Scores

• pRec: 0.110

Haploinsufficiency Scores

• pHI: 0.398
• hipred: Y
• hipred_score: 0.520
• ghis: 0.670

Essentials

• essential_gene_CRISPR2: N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hectd4

Gene ontology

• Biological process: glucose metabolic process;protein ubiquitination;glucose homeostasis
• Cellular component: integral component of membrane
• Molecular function: ubiquitin-protein transferase activity