HERC5

HECT and RLD domain containing E3 ubiquitin protein ligase 5, the group of HECT and RLD domain containing E3 ubiquitin protein ligases

Basic information

Region (hg38): 4:88457119-88506163

Links

ENSG00000138646 ∙ NCBI:51191 ∙ OMIM:608242 ∙ HGNC:24368 ∙ Uniprot:Q9UII4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HERC5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HERC5 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense			59	4	2	65
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	59	5	3

Variants in HERC5

This is a list of pathogenic ClinVar variants found in the HERC5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-88457364-A-G		not specified	Uncertain significance (Apr 25, 2023)
4-88457365-G-T		not specified	Uncertain significance (Jan 26, 2022)
4-88457416-G-C		not specified	Uncertain significance (Oct 26, 2022)
4-88457459-G-A		not specified	Uncertain significance (Jul 06, 2021)
4-88457496-A-G		not specified	Uncertain significance (May 18, 2023)
4-88457515-C-G		not specified	Uncertain significance (Sep 14, 2022)
4-88457522-G-A		not specified	Uncertain significance (Sep 26, 2023)
4-88459398-C-A		not specified	Uncertain significance (Jan 06, 2023)
4-88460121-A-T		not specified	Uncertain significance (Dec 22, 2023)
4-88460162-C-T		not specified	Uncertain significance (Feb 15, 2023)
4-88462281-G-A		not specified	Uncertain significance (Dec 16, 2022)
4-88462290-A-T		not specified	Uncertain significance (Jan 26, 2022)
4-88462317-A-G		not specified	Uncertain significance (Jul 11, 2023)
4-88463538-A-G		not specified	Uncertain significance (Nov 30, 2022)
4-88463543-C-T		not specified	Uncertain significance (Dec 06, 2023)
4-88463547-C-T		not specified	Uncertain significance (Dec 13, 2023)
4-88463588-G-A		not specified	Uncertain significance (Jul 13, 2022)
4-88463609-G-A		not specified	Uncertain significance (Feb 28, 2023)
4-88463883-G-C		not specified	Uncertain significance (Mar 08, 2024)
4-88463975-G-A			Benign (Jun 02, 2018)
4-88463979-G-C			Benign (Jun 02, 2018)
4-88467117-A-G		not specified	Uncertain significance (Jan 17, 2024)
4-88467147-C-T		not specified	Uncertain significance (Apr 25, 2023)
4-88468404-G-C		not specified	Uncertain significance (Feb 16, 2023)
4-88469197-A-G		not specified	Uncertain significance (Jul 14, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HERC5	protein_coding	protein_coding	ENST00000264350	23	49047

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.68e-11	1.00	125688	0	60	125748	0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.845	444	497	0.893	0.0000241	6751
Missense in Polyphen		117	167.37	0.69906		2325
Synonymous	0.217	179	183	0.980	0.00000989	1855
Loss of Function	3.23	25	49.5	0.505	0.00000210	686

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000351	0.000351
Ashkenazi Jewish	0.000300	0.000298
East Asian	0.000275	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000330	0.000325
Middle Eastern	0.000275	0.000272
South Asian	0.000176	0.000163
Other	0.000187	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Major E3 ligase for ISG15 conjugation. Acts as a positive regulator of innate antiviral response in cells induced by interferon. Functions as part of the ISGylation machinery that recognizes target proteins in a broad and relatively non-specific manner. Catalyzes ISGylation of IRF3 which results in sustained activation, it attenuates IRF3-PIN1 interaction, which antagonizes IRF3 ubiquitination and degradation, and boosts the antiviral response. Catalyzes ISGylation of influenza A viral NS1 which attenuates virulence; ISGylated NS1 fails to form homodimers and thus to interact with its RNA targets. Catalyzes ISGylation of papillomavirus type 16 L1 protein which results in dominant- negative effect on virus infectivity. Physically associated with polyribosomes, broadly modifies newly synthesized proteins in a cotranslational manner. In an interferon-stimulated cell, newly translated viral proteins are primary targets of ISG15. {ECO:0000269|PubMed:16407192, ECO:0000269|PubMed:16815975, ECO:0000269|PubMed:16884686, ECO:0000269|PubMed:20133869, ECO:0000269|PubMed:20308324, ECO:0000269|PubMed:20385878, ECO:0000269|PubMed:20542004}.
• Pathway: Cytokine Signaling in Immune system;DDX58/IFIH1-mediated induction of interferon-alpha/beta;Innate Immune System;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;Negative regulators of DDX58/IFIH1 signaling;ISG15 antiviral mechanism;Antiviral mechanism by IFN-stimulated genes;Interferon Signaling (Consensus)

Recessive Scores

• pRec: 0.0787

Intolerance Scores

• loftool: 0.542
• rvis_EVS: -0.82
• rvis_percentile_EVS: 11.98

Haploinsufficiency Scores

• pHI: 0.264
• hipred: N
• hipred_score: 0.454
• ghis: 0.526

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.620

Gene Damage Prediction

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

Gene ontology

• Biological process: regulation of cyclin-dependent protein serine/threonine kinase activity;protein polyubiquitination;ISG15-protein conjugation;negative regulation of type I interferon production;innate immune response;regulation of defense response to virus;defense response to virus
• Cellular component: cytosol;perinuclear region of cytoplasm
• Molecular function: RNA binding;ubiquitin-protein transferase activity;protein binding;ISG15 transferase activity