HECTD3

protein-coding

HECT domain E3 ubiquitin protein ligase 3, the group of HECT domain containing

Gene summary

The protein encoded by this gene transfers ubiquitin from an E2 ubiquitin-conjugating enzyme to targeted substrates, leading to the degradation of those substrates. The encoded protein has been shown to transfer ubiquitin to TRIOBP to facilitate cell cycle progression, and to STX8. [provided by RefSeq, Dec 2012]

MANE transcript

NM_024602.6

Inheritance

—

ClinVar variants

U:116B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr1:45,002,540-45,011,324

External References & Databases

Ensembl (ENSG00000126107)

Transcript & Mutation Effects

hg38 • Region Span ~8.8 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 HECTD3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 107

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024602.6. 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	2 clinvar	2 clinvar	7
missense			107 clinvar	3 clinvar	1 clinvar	111
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	116	5	3	124

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024602.6	RefSeq	NP_078878.3	21	MANE Select
ENST00000372172.5	Ensembl	ENSP00000361245.4	21	MANE Select
ENST00000372168.7	Ensembl	ENSP00000361241.3	13	Standard
ENST00000875134.1	Ensembl	ENSP00000545193.1	21	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 ubiquitination
proteasome-mediated ubiquitin-dependent protein catabolic process

Molecular Function

ubiquitin-protein transferase activity
protein binding
syntaxin binding

Cellular Component

perinuclear region of cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372172
Coding exons: 21
Length: 8790
Individuals with no LoFs: 124782
Homozygous LoFs: 1
Heterozygous LoFs: 36
Defined: 124819
p: 0.000148

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.15	367	503	0.730	0.0000312	5486
Missense (PolyPhen)		96	159.71	0.60109		1697
Synonymous	0.586	188	199	0.947	0.0000116	1745
Loss of Function	4.83	12	48.2	0.249	0.00000248	518

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.000064	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00028	0.00028	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin ligases accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates ubiquitination of TRIOBP and its subsequent proteasomal degradation, thus faciliting cell cycle progression by regulating the turn-over of TRIOBP. Mediates also ubiquitination of STX8 (By similarity). {ECO:0000250|UniProtKB:Q3U487, ECO:0000269|PubMed:18194665}.;

Recessive Scores

pRec: 0.117

Intolerance Scores

LoFtool: 0.637
RVIS EVS: -0.91
RVIS percentile EVS: 10.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.857

Gene Damage Prediction

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