UBE2I

protein-coding

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

Gene summary

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. Four alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003345.5

Inheritance

—

ClinVar variants

U:1

Top phenotype

See cases

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr16:1,291,444-1,327,018

External References & Databases

Ensembl (ENSG00000103275)

Transcript & Mutation Effects

hg38 • Region Span ~35.6 kb

Loading mutation effect viewer...

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 UBE2I variants in ClinVar

1 Conditions Cataloged

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003345.5. 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						0
missense			1 clinvar			1
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	1	0	0	1

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 85 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003345.5	RefSeq	NP_003336.1	6	MANE Select
ENST00000397514.8	Ensembl	ENSP00000380649.3	6	MANE Select
NM_194259.3	RefSeq	NP_919235.1	6	Standard
NM_194260.3	RefSeq	NP_919236.1	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ube2ib	Danio rerio	Structure: chondrocyte Quality: increased size abnormal

Gene / Model

Organism

Observed Phenotype

ube2ib

Danio rerio

Structure: chondrocyte

Quality: increased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ubiquitin mediated proteolysis - Homo sapiens (human)
RNA transport - Homo sapiens (human)
MicroRNAs in cancer - Homo sapiens (human)
NF-kappa B signaling pathway - Homo sapiens (human)
Androgen receptor signaling pathway

Biological Process

negative regulation of transcription by RNA polymerase II
cellular protein modification process
ubiquitin-dependent protein catabolic process
cell cycle
chromosome segregation

Molecular Function

RNA binding
ubiquitin-protein transferase activity
protein binding
ATP binding
protein C-terminus binding

Cellular Component

synaptonemal complex
fibrillar center
nucleus
nuclear envelope
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000355803
Coding exons: 6
Length: 21472
Individuals with no LoFs: 125579
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125580
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.10	9	93.0	0.0967	0.00000535	1030
Missense (PolyPhen)		1	23.501	0.042551		307
Synonymous	-2.41	60	40.5	1.48	0.00000293	287
Loss of Function	2.99	0	10.4	0.00	4.42e-7	121

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)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3, SUMO4 and SUMO1P1/SUMO5 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2, CBX4 and ZNF451. Can catalyze the formation of poly-SUMO chains. Necessary for sumoylation of FOXL2 and KAT5. Essential for nuclear architecture and chromosome segregation. Sumoylates p53/TP53 at 'Lys-386'. {ECO:0000269|PubMed:11451954, ECO:0000269|PubMed:15809060, ECO:0000269|PubMed:17466333, ECO:0000269|PubMed:19638400, ECO:0000269|PubMed:19744555, ECO:0000269|PubMed:20077568, ECO:0000269|PubMed:26524494, ECO:0000269|PubMed:27211601, ECO:0000269|PubMed:8668529}.;

Recessive Scores

pRec: 0.474

Intolerance Scores

LoFtool: 0.348
RVIS EVS: -0.1
RVIS percentile EVS: 46.2

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.544

Gene Damage Prediction

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