UBE2M

protein-coding

ubiquitin conjugating enzyme E2 M, 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. The encoded protein is linked with a ubiquitin-like protein, NEDD8, which can be conjugated to cellular proteins, such as Cdc53/culin. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003969.4

Inheritance

—

ClinVar variants

U:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr19:58,555,712-58,558,954

External References & Databases

Ensembl (ENSG00000130725)

Transcript & Mutation Effects

hg38 • Region Span ~3.2 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 UBE2M variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003969.4. 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						0
missense			13 clinvar			13
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	15	0	0	15

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003969.4	RefSeq	NP_003960.1	6	MANE Select
ENST00000253023.8	Ensembl	ENSP00000253023.2	6	MANE Select
ENST00000595957.5	Ensembl	ENSP00000468940.1	3	Standard
ENST00000596985.1	Ensembl	ENSP00000469855.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ubiquitin mediated proteolysis - Homo sapiens (human)
regulation of p27 phosphorylation during cell cycle progression
Signal Transduction
Post-translational protein modification
protein ubiquitylation

Biological Process

cellular protein modification process
protein ubiquitination
positive regulation of neuron apoptotic process
post-translational protein modification
protein neddylation

Molecular Function

ubiquitin-protein transferase activity
protein binding
ATP binding
NEDD8 transferase activity

Cellular Component

nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000253023
Coding exons: 6
Length: 3249
Individuals with no LoFs: 113661
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 113667
p: 0.0000264

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.29	40	107	0.375	0.00000604	1202
Missense (PolyPhen)		6	44.05	0.13621		506
Synonymous	-0.487	50	45.8	1.09	0.00000282	330
Loss of Function	2.58	1	9.64	0.104	4.09e-7	120

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	0.000064	0.000064	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000030	0.000030	rare
South Asian	0.000068	0.000068	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Accepts the ubiquitin-like protein NEDD8 from the UBA3- NAE1 E1 complex and catalyzes its covalent attachment to other proteins. The specific interaction with the E3 ubiquitin ligase RBX1, but not RBX2, suggests that the RBX1-UBE2M complex neddylates specific target proteins, such as CUL1, CUL2, CUL3 and CUL4. Involved in cell proliferation. {ECO:0000269|PubMed:10207026, ECO:0000269|PubMed:15361859}.;

Recessive Scores

pRec: 0.142

Intolerance Scores

LoFtool: 0.361
RVIS EVS: 0.13
RVIS percentile EVS: 62.74

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.781

Gene Damage Prediction

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