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

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.

• Neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum (2 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				7	6	13
missense			159	9		168
nonsense	1	1				2
start loss						0
frameshift	1	1				2
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region				1		1
non coding			1	1		2
Total	2	3	161	17	6

Variants in HECTD4

This is a list of pathogenic ClinVar variants found in the HECTD4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-112163079-C-T			Benign/Likely benign (Sep 01, 2022)
12-112163550-A-C		not specified	Uncertain significance (Jan 23, 2023)
12-112163564-T-C		not specified	Uncertain significance (Dec 20, 2023)
12-112163610-T-C		not specified	Uncertain significance (Oct 03, 2022)
12-112163651-C-T		not specified	Uncertain significance (Dec 05, 2022)
12-112163660-G-A		not specified	Uncertain significance (Nov 05, 2021)
12-112163696-A-C		not specified	Uncertain significance (Feb 21, 2024)
12-112163713-C-T			Likely benign (Aug 01, 2024)
12-112163721-T-C		not specified	Uncertain significance (Jul 26, 2022)
12-112164116-G-C		not specified	Uncertain significance (Mar 07, 2024)
12-112164124-C-T		not specified	Uncertain significance (Aug 02, 2023)
12-112164214-G-A		not specified	Uncertain significance (Mar 22, 2023)
12-112167318-C-G		HECTD4-related disorder	Uncertain significance (Dec 11, 2023)
12-112167334-C-T		not specified	Uncertain significance (Dec 15, 2023)
12-112167363-T-C		HECTD4-related disorder	Likely benign (Feb 01, 2022)
12-112167391-C-T		not specified	Uncertain significance (Jun 09, 2022)
12-112167392-G-A			Benign (Aug 03, 2017)
12-112167443-G-A			Benign (Jan 19, 2018)
12-112167501-C-G		not specified	Uncertain significance (Dec 26, 2023)
12-112167507-G-A		not specified	Uncertain significance (Jan 09, 2024)
12-112167857-G-A		not specified	Uncertain significance (Sep 14, 2023)
12-112167863-G-A		not specified	Uncertain significance (May 07, 2024)
12-112167869-C-A		not specified	Uncertain significance (Jan 03, 2024)
12-112167869-C-T		not specified	Uncertain significance (Nov 08, 2021)
12-112167887-A-G		not specified	Uncertain significance (Aug 17, 2022)

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