UBE2D2

protein-coding

ubiquitin conjugating enzyme E2 D2, the group of Ubiquitin conjugating enzymes E2

Gene summary

Regulated degradation of misfolded, damaged or short-lived proteins in eukaryotes occurs via the ubiquitin (Ub)-proteasome system (UPS). An integral part of the UPS system is the ubiquitination of target proteins and covalent linkage of Ub-containing proteins to form polymeric chains, marking them as targets for 26S proteasome-mediated degradation. Ubiquitination of proteins is mediated by a cascade of enzymes which includes E1 (ubiquitin activating), E2 (ubiquitin conjugating), and E3 (ubiquitin ligases) enzymes. This gene encodes a member of the E2 enzyme family. Substrates of this enzyme include the tumor suppressor protein p53 and peroxisomal biogenesis factor 5 (PEX5). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

MANE transcript

NM_003339.3

Inheritance

—

ClinVar variants

U:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr5:139,526,431-139,628,434

External References & Databases

Ensembl (ENSG00000131508)

Transcript & Mutation Effects

hg38 • Region Span ~102.0 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 UBE2D2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003339.3. 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						0
missense			5 clinvar			5
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	9	0	0	9

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003339.3	RefSeq	NP_003330.1	7	MANE Select
ENST00000398733.8	Ensembl	ENSP00000381717.3	7	MANE Select
NM_181838.2	RefSeq	NP_862821.1	6	Standard
ENST00000398734.8	Ensembl	ENSP00000381718.4	7	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ube2d2	Danio rerio	Structure: somite Quality: increased amount abnormal

Gene / Model

Organism

Observed Phenotype

ube2d2

Danio rerio

Structure: somite

Quality: increased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ubiquitin mediated proteolysis - Homo sapiens (human)
Protein processing in endoplasmic reticulum - Homo sapiens (human)
Shigellosis - Homo sapiens (human)
Proteasome Degradation
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha

Biological Process

protein polyubiquitination
cellular protein modification process
ubiquitin-dependent protein catabolic process
protein targeting to peroxisome
protein ubiquitination

Molecular Function

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

Cellular Component

ubiquitin ligase complex
nucleoplasm
cytosol
protein-containing complex
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000398733
Coding exons: 7
Length: 102003
Individuals with no LoFs: 123823
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 123824
p: 0.00000404

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.96	6	80.9	0.0741	0.00000407	963
Missense (PolyPhen)		2	25.522	0.078364		359
Synonymous	0.969	19	25.2	0.754	0.00000114	273
Loss of Function	3.00	0	10.5	0.00	5.41e-7	123

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00010	0.00010	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
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 catalyzes 'Lys- 48'-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP- induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and autoubiquitination of STUB1 and TRAF6. Involved in the signal-induced conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent degradation of p53/TP53 and the activation of MAVS in the mitochondria by DDX58/RIG-I in response to viral infection. Essential for viral activation of IRF3. {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:15280377, ECO:0000269|PubMed:18042044, ECO:0000269|PubMed:18359941, ECO:0000269|PubMed:18703417, ECO:0000269|PubMed:19854139, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:20403326, ECO:0000269|PubMed:20525694}.;

Recessive Scores

pRec: 0.250

Intolerance Scores

RVIS EVS: 0.1
RVIS percentile EVS: 60.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.247

Gene Damage Prediction

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