UBA6

protein-coding

ubiquitin like modifier activating enzyme 6, the group of Ubiquitin like modifier activating enzymes

Gene summary

Modification of proteins with ubiquitin (UBB; MIM 191339) or ubiquitin-like proteins controls many signaling networks and requires a ubiquitin-activating enzyme (E1), a ubiquitin conjugating enzyme (E2), and a ubiquitin protein ligase (E3). UBE1L2 is an E1 enzyme that initiates the activation and conjugation of ubiquitin-like proteins (Jin et al., 2007 [PubMed 17597759]).[supplied by OMIM, Mar 2008]

Previous symbols:

UBE1L2

MANE transcript

NM_018227.6

Inheritance

ClinVar variants

U:144B:7

Top phenotype

Autism spectrum disorder

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr4:67,612,652-67,701,155

External References & Databases

Ensembl (ENSG00000033178)

Transcript & Mutation Effects

hg38 • Region Span ~88.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual disabilityLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0001071

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to UBA6 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 134

not providedTotal: 3

Autism spectrum disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018227.6. 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			2 clinvar	2 clinvar		4
missense			139 clinvar	5 clinvar		144
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	144	7	0	151

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018227.6	RefSeq	NP_060697.4	33	MANE Select
ENST00000322244.10	Ensembl	ENSP00000313454.4	33	MANE Select
ENST00000420827.2	Ensembl	ENSP00000399234.2	13	Standard
ENST00000420827.3	Ensembl	ENSP00000399234.2	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ubiquitin mediated proteolysis - Homo sapiens (human)
Post-translational protein modification
protein ubiquitylation
Metabolism of proteins
Synthesis of active ubiquitin: roles of E1 and E2 enzymes

Biological Process

ubiquitin-dependent protein catabolic process
learning
locomotory behavior
protein ubiquitination
amygdala development

Molecular Function

ubiquitin activating enzyme activity
protein binding
ATP binding
FAT10 activating enzyme activity

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000322244
Coding exons: 33
Length: 88528
Individuals with no LoFs: 125659
Homozygous LoFs: 0
Heterozygous LoFs: 89
Defined: 125748
p: 0.000354

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.10	461	532	0.866	0.0000257	6928
Missense (PolyPhen)		111	165.05	0.67253		2014
Synonymous	0.641	165	176	0.939	0.00000852	1909
Loss of Function	4.43	26	64.3	0.404	0.00000324	821

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0010	0.00098	notable
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00052	0.00050	rare
East Asian	0.00055	0.00054	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00037	0.00036	rare
South Asian	0.00019	0.00016	rare
Other	0.00066	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin- E1 thioester and free AMP. Specific for ubiquitin, does not activate ubiquitin-like peptides. Differs from UBE1 in its specificity for substrate E2 charging. Does not charge cell cycle E2s, such as CDC34. Essential for embryonic development. Required for UBD/FAT10 conjugation. Isoform 2 may play a key role in ubiquitin system and may influence spermatogenesis and male fertility. {ECO:0000269|PubMed:15202508, ECO:0000269|PubMed:17597759, ECO:0000269|PubMed:17889673}.;

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.658
RVIS EVS: -0.97
RVIS percentile EVS: 8.9

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.665

Gene Damage Prediction

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