HERC4

HECT and RLD domain containing E3 ubiquitin protein ligase 4, the group of HECT and RLD domain containing E3 ubiquitin protein ligases

Basic information

Region (hg38): 10:67921899-68075301

Links

ENSG00000148634 ∙ NCBI:26091 ∙ OMIM:609248 ∙ HGNC:24521 ∙ Uniprot:Q5GLZ8 ∙ 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 HERC4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HERC4 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				2		2
missense			35	2		37
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	35	4	1

Variants in HERC4

This is a list of pathogenic ClinVar variants found in the HERC4 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-67922953-T-C		not specified	Uncertain significance (Feb 21, 2024)
10-67922965-G-A		not specified	Uncertain significance (Jun 09, 2022)
10-67922971-A-T		not specified	Uncertain significance (Dec 06, 2021)
10-67923068-C-T		not specified	Uncertain significance (May 03, 2023)
10-67923076-T-C		not specified	Uncertain significance (Aug 22, 2023)
10-67925118-C-T		not specified	Uncertain significance (Nov 27, 2023)
10-67925124-A-C		not specified	Uncertain significance (May 16, 2023)
10-67925130-C-T		not specified	Uncertain significance (Mar 25, 2024)
10-67932634-A-G		not specified	Uncertain significance (May 30, 2023)
10-67932719-C-T			Likely benign (Sep 01, 2023)
10-67932731-C-T		not specified	Uncertain significance (Apr 13, 2022)
10-67932788-TG-T			Benign (Apr 04, 2018)
10-67940946-C-T		not specified	Uncertain significance (Jul 03, 2024)
10-67941075-T-C		not specified	Uncertain significance (Jun 29, 2022)
10-67954624-C-T		not specified	Uncertain significance (Aug 02, 2021)
10-67954629-T-C		not specified	Uncertain significance (Dec 15, 2022)
10-67955039-C-T		not specified	Uncertain significance (Aug 01, 2022)
10-67955075-A-G		not specified	Uncertain significance (Aug 02, 2021)
10-67956948-G-T		not specified	Uncertain significance (Sep 28, 2021)
10-67959128-G-C		not specified	Uncertain significance (May 07, 2024)
10-67966786-C-T		not specified	Uncertain significance (Feb 17, 2024)
10-67988707-T-A		not specified	Uncertain significance (Dec 15, 2022)
10-67988712-A-T		not specified	Uncertain significance (Nov 11, 2024)
10-67988741-G-C		not specified	Uncertain significance (Mar 29, 2023)
10-67990239-G-C		not specified	Uncertain significance (Dec 08, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HERC4	protein_coding	protein_coding	ENST00000395198	24	153441

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000395	125731	0	13	125744	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.31	256	537	0.477	0.0000256	6948
Missense in Polyphen		42	175.34	0.23953		2259
Synonymous	1.59	162	190	0.854	0.00000937	1975
Loss of Function	5.88	7	53.4	0.131	0.00000235	715

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000154	0.000154
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000714	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable E3 ubiquitin-protein ligase involved in either protein trafficking or in the distribution of cellular structures. Required for spermatozoon maturation and fertility, and for the removal of the cytoplasmic droplet of the spermatozoon. E3 ubiquitin-protein ligases accept ubiquitin from an E2 ubiquitin- conjugating enzyme in the form of a thioester and then directly transfer it to targeted substrates. {ECO:0000250|UniProtKB:Q6PAV2}.
• Pathway: Ubiquitin mediated proteolysis - Homo sapiens (human);Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.409
• rvis_EVS: -1.09
• rvis_percentile_EVS: 7.11

Haploinsufficiency Scores

• pHI: 0.330
• hipred: Y
• hipred_score: 0.563
• ghis: 0.653

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.679

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Herc4
• Phenotype: reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); skeleton phenotype; hearing/vestibular/ear phenotype; cellular phenotype

Gene ontology

• Biological process: spermatogenesis;protein ubiquitination;cell differentiation
• Cellular component: fibrillar center;cytosol
• Molecular function: ubiquitin-protein transferase activity