HECTD2

protein-coding

HECT domain E3 ubiquitin protein ligase 2, the group of HECT domain containing

Gene summary

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein polyubiquitination. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_182765.6

Inheritance

—

ClinVar variants

U:63B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr10:91,409,280-91,514,829

External References & Databases

Ensembl (ENSG00000165338)

Transcript & Mutation Effects

hg38 • Region Span ~105.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HECTD2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 62

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_182765.6. 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			3 clinvar	1 clinvar	2 clinvar	6
missense			57 clinvar	7 clinvar		64
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	63	8	2	73

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_182765.6	RefSeq	NP_877497.4	21	MANE Select
ENST00000298068.10	Ensembl	ENSP00000298068.5	21	MANE Select
NM_001284274.3	RefSeq	NP_001271203.2	22	Standard
NM_001348365.2	RefSeq	NP_001335294.1	19	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 polyubiquitination

Molecular Function

ubiquitin-protein transferase activity

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000298068
Coding exons: 21
Length: 104491
Individuals with no LoFs: 125684
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125691
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	4.11	161	389	0.414	0.0000194	5059
Missense (PolyPhen)		13	101.59	0.12796		1332
Synonymous	1.95	110	139	0.790	0.00000719	1404
Loss of Function	5.36	6	44.7	0.134	0.00000233	572

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000068	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000037	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable 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|UniProtKB:Q69ZR2}.;

Recessive Scores

pRec: 0.0961

Intolerance Scores

LoFtool: 0.478
RVIS EVS: -0.09
RVIS percentile EVS: 46.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.331

Gene Damage Prediction

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