HERC3

protein-coding

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

Gene summary

This gene encodes a member the HERC ubiquitin ligase family. The encoded protein is located in the cytosol and binds ubiquitin via a HECT domain. Mutations in this gene have been associated with colorectal and gastric carcinomas. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

MANE transcript

NM_014606.3

Inheritance

—

ClinVar variants

U:103B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr4:88,592,434-88,708,539

External References & Databases

Ensembl (ENSG00000138641)

Transcript & Mutation Effects

hg38 • Region Span ~116.1 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 HERC3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 130

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014606.3. 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			4 clinvar	2 clinvar		6
missense			90 clinvar	1 clinvar		91
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	103	3	0	106

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014606.3	RefSeq	NP_055421.1	24	MANE Select
ENST00000402738.6	Ensembl	ENSP00000385684.1	24	MANE Select
NM_001271602.2	RefSeq	NP_001258531.1	23	Standard
NM_001318505.2	RefSeq	NP_001305434.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ubiquitin mediated proteolysis - Homo sapiens (human)
Immune System
Adaptive Immune System
Antigen processing: Ubiquitination & Proteasome degradation
Class I MHC mediated antigen processing & presentation

Biological Process

protein ubiquitination

Molecular Function

ubiquitin-protein transferase activity

Cellular Component

cytosol
cytoplasmic vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000402738
Coding exons: 24
Length: 187495
Individuals with no LoFs: 125714
Homozygous LoFs: 0
Heterozygous LoFs: 34
Defined: 125748
p: 0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.21	338	550	0.614	0.0000266	6906
Missense (PolyPhen)		105	244.82	0.42889		3053
Synonymous	0.579	197	208	0.949	0.0000105	1995
Loss of Function	5.23	14	56.4	0.248	0.00000264	694

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00033	0.00033	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

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. {ECO:0000250}.;

Recessive Scores

pRec: 0.121

Intolerance Scores

LoFtool: 0.478
RVIS EVS: -0.38
RVIS percentile EVS: 28.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.811

Gene Damage Prediction

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