HECTD1

protein-coding

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

Gene summary

Enables ubiquitin protein ligase activity. Predicted to be involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Predicted to act upstream of or within several processes, including chordate embryonic development; circulatory system development; and protein ubiquitination. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_015382.4

Inheritance

ClinVar variants

P:10U:292B:16

Top phenotype

Neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr14:31,100,117-31,207,804

External References & Databases

Ensembl (ENSG00000092148)

Transcript & Mutation Effects

hg38 • Region Span ~107.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

neural tube defectLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0018075

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HECTD1 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 209

not providedTotal: 93

Neurodevelopmental disorderTotal: 4

HECTD1-related disorderTotal: 4

HECTD1-associated neurodevelopmental disorderTotal: 1

Absence seizureTotal: 1

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015382.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	8 clinvar	5 clinvar	18
missense		4 clinvar	270 clinvar	1 clinvar	2 clinvar	277
nonsense	4 clinvar		5 clinvar			9
start loss						0
frameshift	1 clinvar	1 clinvar	4 clinvar			6
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	5	5	292	9	7	318

Highest pathogenic variant AF is 0.0000043370883

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 95 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015382.4	RefSeq	NP_056197.3	42	MANE Select
ENST00000399332.6	Ensembl	ENSP00000382269.1	42	MANE Select
NM_001411010.1	RefSeq	NP_001397939.1	42	Standard
NM_001437347.1	RefSeq	NP_001424276.1	42	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Immune System
Adaptive Immune System
Antigen processing: Ubiquitination & Proteasome degradation
Class I MHC mediated antigen processing & presentation

Biological Process

protein K63-linked ubiquitination

Molecular Function

ubiquitin-protein transferase activity
protein binding
metal ion binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000399332
Coding exons: 42
Length: 107693
Individuals with no LoFs: 124764
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 124792
p: 0.000112

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	5.01	869	1.40e+3	0.623	0.0000750	16996
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00026	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.000093	0.000093	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.104

Intolerance Scores

LoFtool: 0.365
RVIS EVS: -2.23
RVIS percentile EVS: 1.33

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Indispensability pred.: E
Indispensability score: 0.985

Gene Damage Prediction

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