UBE4B

protein-coding

ubiquitination factor E4B, the group of U-box domain containing

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 an additional conjugation factor, E4, which is involved in multiubiquitin chain assembly. This gene is also the strongest candidate in the neuroblastoma tumor suppressor genes. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001105562.3

Inheritance

—

ClinVar variants

U:151B:10

Top phenotype

Developmental disorder

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr1:10,032,832-10,181,239

External References & Databases

Ensembl (ENSG00000130939)

Transcript & Mutation Effects

hg38 • Region Span ~148.4 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 UBE4B variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 128

not providedTotal: 17

Developmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001105562.3. 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			7 clinvar	4 clinvar	2 clinvar	13
missense			133 clinvar	2 clinvar	2 clinvar	137
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	151	6	4	161

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 59 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001105562.3	RefSeq	NP_001099032.1	28	MANE Select
ENST00000343090.11	Ensembl	ENSP00000343001.6	28	MANE Select
NM_001410744.1	RefSeq	NP_001397673.1	29	Standard
NM_006048.5	RefSeq	NP_006039.2	27	Standard

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)
p73 transcription factor network

Biological Process

protein polyubiquitination
ventricular trabecula myocardium morphogenesis
ubiquitin-dependent protein catabolic process
protein monoubiquitination
granzyme-mediated apoptotic signaling pathway

Molecular Function

ATP binding
enzyme binding
ubiquitin-ubiquitin ligase activity
ATPase binding

Cellular Component

ubiquitin ligase complex
nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000343090
Coding exons: 28
Length: 148408
Individuals with no LoFs: 125597
Homozygous LoFs: 0
Heterozygous LoFs: 150
Defined: 125747
p: 0.000597

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.73	488	781	0.625	0.0000471	8556
Missense (PolyPhen)		68	197.64	0.34406		2086
Synonymous	0.677	284	299	0.950	0.0000188	2554
Loss of Function	7.02	5	67.0	0.0747	0.00000358	763

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000090	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00026	0.00023	rare
European (Non-Finnish)	0.0013	0.0012	notable
South Asian	0.000033	0.000033	rare
Other	0.00088	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases (By similarity). May also function as an E4 ligase mediating the assembly of polyubiquitin chains on substrates ubiquitinated by another E3 ubiquitin ligase (By similarity). May regulate myosin assembly in striated muscles together with STUB1 and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation (PubMed:17369820). {ECO:0000250|UniProtKB:P54860, ECO:0000250|UniProtKB:Q9ES00, ECO:0000269|PubMed:17369820}.;

Recessive Scores

pRec: 0.133

Intolerance Scores

LoFtool: 0.283
RVIS EVS: -1.39
RVIS percentile EVS: 4.31

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.788

Gene Damage Prediction

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