HECTD1

HECT domain E3 ubiquitin protein ligase 1, the group of Armadillo like helical domain containing|Ankyrin repeat domain containing|HECT domain containing

Basic information

Region (hg38): 14:31100117-31207804

Links

ENSG00000092148 ∙ NCBI:25831 ∙ OMIM:618649 ∙ HGNC:20157 ∙ Uniprot:Q9ULT8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder (Moderate), mode of inheritance: AD
• neural tube defect (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HECTD1 gene.

• not_specified (168 variants)
• not_provided (47 variants)
• HECTD1-related_disorder (3 variants)
• HECTD1-associated_neurodevelopmental_disorder (1 variants)
• Intellectual_disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HECTD1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015382.4. 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				7	5	12
missense			190	1	2	193
nonsense	2		3			5
start loss						0
frameshift			4			4
splice donor/acceptor (+/-2bp)						0
Total	2	0	197	8	7

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HECTD1	protein_coding	protein_coding	ENST00000399332	42	107693

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	5.69e-13	124764	0	28	124792	0.000112

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.01	869	1.40e+3	0.623	0.0000750	16996
Missense in Polyphen		289	611.9	0.4723		7339
Synonymous	0.992	454	482	0.943	0.0000243	5113
Loss of Function	9.81	14	139	0.101	0.00000837	1621

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000287	0.000287
Ashkenazi Jewish	0.00	0.00
East Asian	0.000223	0.000223
Finnish	0.0000928	0.0000928
European (Non-Finnish)	0.000133	0.000132
Middle Eastern	0.000223	0.000223
South Asian	0.0000654	0.0000654
Other	0.00	0.00

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. Mediates 'Lys-63'-linked polyubiquitination of HSP90AA1 which leads to its intracellular localization and reduced secretion. Negatively regulating HSP90AA1 secretion in cranial mesenchyme cells may impair their emigration and may be essential for the correct development of the cranial neural folds and neural tube closure. {ECO:0000250|UniProtKB:Q69ZR2}.
• Pathway: Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

• pRec: 0.104

Intolerance Scores

• loftool: 0.365
• rvis_EVS: -2.23
• rvis_percentile_EVS: 1.33

Haploinsufficiency Scores

• pHI: 0.712
• hipred: Y
• hipred_score: 0.563
• ghis: 0.643

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.985

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hectd1
• Phenotype: growth/size/body region phenotype; craniofacial phenotype; skeleton phenotype; embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype

Gene ontology

• Biological process: protein K63-linked ubiquitination
• Molecular function: ubiquitin-protein transferase activity;protein binding;metal ion binding