UBE2K

protein-coding

ubiquitin conjugating enzyme E2 K, the group of Ubiquitin conjugating enzymes E2

Gene summary

The protein encoded by this gene belongs to the ubiquitin-conjugating enzyme family. This protein interacts with RING finger proteins, and it can ubiquitinate huntingtin, the gene product for Huntington's disease. Known functions for this protein include a role in aggregate formation of expanded polyglutamine proteins and the suppression of apoptosis in polyglutamine diseases, a role in the dislocation of newly synthesized MHC class I heavy chains from the endoplasmic reticulum, and involvement in foam cell formation. Multiple transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

HIP2

MANE transcript

NM_005339.5

Inheritance

—

ClinVar variants

U:4B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr4:39,698,109-39,782,792

External References & Databases

Ensembl (ENSG00000078140)

Transcript & Mutation Effects

hg38 • Region Span ~84.7 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 UBE2K variants in ClinVar

1 Conditions Cataloged

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005339.5. 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
missense			1 clinvar	1 clinvar		2
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	4	1	0	5

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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_005339.5	RefSeq	NP_005330.1	7	MANE Select
ENST00000261427.10	Ensembl	ENSP00000261427.5	7	MANE Select
NM_001111112.2	RefSeq	NP_001104582.1	6	Standard
NM_001111113.2	RefSeq	NP_001104583.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ubiquitin mediated proteolysis - Homo sapiens (human)
Post-translational protein modification
protein ubiquitylation
Metabolism of proteins
Synthesis of active ubiquitin: roles of E1 and E2 enzymes

Biological Process

ubiquitin-dependent protein catabolic process
positive regulation of peptidyl-threonine phosphorylation
free ubiquitin chain polymerization
protein ubiquitination
regulation of proteasomal ubiquitin-dependent protein catabolic process

Molecular Function

ubiquitin-protein transferase activity
protein binding
ATP binding
ubiquitin protein ligase binding
ubiquitin-ubiquitin ligase activity

Cellular Component

nucleus
cytosol
filopodium tip

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000261427
Coding exons: 7
Length: 84749
Individuals with no LoFs: 121023
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 121024
p: 0.00000413

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.23	12	105	0.114	0.00000516	1298
Missense (PolyPhen)		1	34.764	0.028765		412
Synonymous	1.09	28	36.4	0.770	0.00000174	378
Loss of Function	3.34	0	13.0	0.00	6.15e-7	152

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000090	0.0000090	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, in the presence or in the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex, catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains. Does not transfer ubiquitin directly to but elongates monoubiquitinated substrate protein. Mediates the selective degradation of short-lived and abnormal proteins, such as the endoplasmic reticulum-associated degradation (ERAD) of misfolded lumenal proteins. Ubiquitinates huntingtin. May mediate foam cell formation by the suppression of apoptosis of lipid-bearing macrophages through ubiquitination and subsequence degradation of p53/TP53. Proposed to be involved in ubiquitination and proteolytic processing of NF-kappa-B; in vitro supports ubiquitination of NFKB1. In case of infection by cytomegaloviruses may be involved in the US11-dependent degradation of MHC class I heavy chains following their export from the ER to the cytosol. In case of viral infections may be involved in the HPV E7 protein- dependent degradation of RB1. {ECO:0000269|PubMed:10634809, ECO:0000269|PubMed:10675012, ECO:0000269|PubMed:16714285, ECO:0000269|PubMed:16868077, ECO:0000269|PubMed:17873885, ECO:0000269|PubMed:19906396, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:8702625}.;

Recessive Scores

pRec: 0.124

Intolerance Scores

RVIS EVS: 0.06
RVIS percentile EVS: 58

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.914

Gene Damage Prediction

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