UBA7

protein-coding

ubiquitin like modifier activating enzyme 7, the group of Ubiquitin like modifier activating enzymes|MicroRNA protein coding host genes

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 E1 ubiquitin-activating enzyme family. The encoded enzyme is a retinoid target that triggers promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARalpha) degradation and apoptosis in acute promyelocytic leukemia, where it is involved in the conjugation of the ubiquitin-like interferon-stimulated gene 15 protein. [provided by RefSeq, Jul 2008]

Previous symbols:

UBE1L

MANE transcript

NM_003335.3

Inheritance

—

ClinVar variants

U:159B:23

Top phenotype

UBA7-related disorder

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr3:49,805,209-49,813,953

External References & Databases

Ensembl (ENSG00000182179)

Transcript & Mutation Effects

hg38 • Region Span ~8.7 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 UBA7 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 154

UBA7-related disorderTotal: 11

not providedTotal: 4

See casesTotal: 2

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003335.3. 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			3 clinvar	5 clinvar	2 clinvar	10
missense			148 clinvar	14 clinvar	2 clinvar	164
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	159	19	4	182

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 68 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003335.3	RefSeq	NP_003326.2	24	MANE Select
ENST00000333486.4	Ensembl	ENSP00000333266.3	24	MANE Select
ENST00000905598.1	Ensembl	ENSP00000575657.1	23	Standard
ENST00000905598.2	Ensembl	ENSP00000575657.1	23	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ubiquitin mediated proteolysis - Homo sapiens (human)
Parkinson,s disease - Homo sapiens (human)
Proteasome Degradation
Parkinsons Disease Pathway
DNA Repair

Biological Process

cellular protein modification process
cellular response to DNA damage stimulus
protein ubiquitination
modification-dependent protein catabolic process
ISG15-protein conjugation

Molecular Function

ubiquitin-protein transferase activity
protein binding
ATP binding
ISG15 activating enzyme activity

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000333486
Coding exons: 24
Length: 8740
Individuals with no LoFs: 125314
Homozygous LoFs: 4
Heterozygous LoFs: 430
Defined: 125748
p: 0.00173

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.988	507	574	0.884	0.0000328	6504
Missense (PolyPhen)		130	174.05	0.74692		2179
Synonymous	0.308	232	238	0.975	0.0000133	2131
Loss of Function	2.18	34	50.8	0.670	0.00000246	570

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0015	0.0015	notable
Latino/Admixed American	0.0017	0.0017	notable
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00050	0.00049	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.0013	0.0012	notable
South Asian	0.0060	0.0058	notable
Other	0.0031	0.0031	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Activates ubiquitin by first adenylating with ATP its C- terminal glycine residue and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin- E1 thioester and free AMP. Catalyzes the ISGylation of influenza A virus NS1 protein. {ECO:0000269|PubMed:16254333, ECO:0000269|PubMed:20133869}.;

Recessive Scores

pRec: 0.145

Intolerance Scores

LoFtool: 0.935
RVIS EVS: 0.25
RVIS percentile EVS: 69.66

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.235

Gene Damage Prediction

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