HERC6

protein-coding

HECT and RLD domain containing E3 ubiquitin protein ligase family member 6, the group of HECT and RLD domain containing E3 ubiquitin protein ligases

Gene summary

HERC6 belongs to the HERC family of ubiquitin ligases, all of which contain a HECT domain and at least 1 RCC1 (MIM 179710)-like domain (RLD). The 350-amino acid HECT domain is predicted to catalyze the formation of a thioester with ubiquitin before transferring it to a substrate, and the RLD is predicted to act as a guanine nucleotide exchange factor for small G proteins (Hochrainer et al., 2005 [PubMed 15676274]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_017912.4

Inheritance

—

ClinVar variants

U:149B:16

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr4:88,378,739-88,443,097

External References & Databases

Ensembl (ENSG00000138642)

Transcript & Mutation Effects

hg38 • Region Span ~64.4 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 HERC6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 141

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017912.4. 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			2 clinvar		2 clinvar	4
missense			139 clinvar	9 clinvar	4 clinvar	152
nonsense					1 clinvar	1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	149	9	7	165

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017912.4	RefSeq	NP_060382.3	23	MANE Select
ENST00000264346.12	Ensembl	ENSP00000264346.8	23	MANE Select
NM_001165136.2	RefSeq	NP_001158608.1	22	Standard
ENST00000380265.10	Ensembl	ENSP00000369617.5	22	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
hematopoietic progenitor cell differentiation
response to bacterium

Molecular Function

ubiquitin-protein transferase activity

Cellular Component

nucleus
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264346
Coding exons: 23
Length: 64373
Individuals with no LoFs: 125493
Homozygous LoFs: 0
Heterozygous LoFs: 226
Defined: 125719
p: 0.000899

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.16	424	497	0.854	0.0000247	6656
Missense (PolyPhen)		140	162.52	0.86141		2320
Synonymous	1.30	160	182	0.878	0.00000951	1888
Loss of Function	2.16	29	44.6	0.651	0.00000207	629

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00042	0.00037	rare
Latino/Admixed American	0.00021	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00039	0.00038	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00035	0.00034	rare
South Asian	0.0052	0.0052	notable
Other	0.00033	0.00033	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: 0.0805

Intolerance Scores

LoFtool: 0.473
RVIS EVS: 1.94
RVIS percentile EVS: 97.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.337

Gene Damage Prediction

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