UBA6

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

Basic information

Region (hg38): 4:67612652-67701155

Previous symbols: [ "UBE1L2" ]

Links

ENSG00000033178 ∙ NCBI:55236 ∙ OMIM:611361 ∙ HGNC:25581 ∙ Uniprot:A0AVT1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UBA6 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UBA6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2		2
missense			74	1		75
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	74	3	0

Variants in UBA6

This is a list of pathogenic ClinVar variants found in the UBA6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-67619020-A-G		not specified	Uncertain significance (Feb 27, 2024)
4-67619052-T-C		not specified	Uncertain significance (Dec 27, 2022)
4-67619092-C-A		not specified	Uncertain significance (Mar 01, 2023)
4-67619112-G-T		not specified	Uncertain significance (Jan 04, 2022)
4-67619113-G-A		not specified	Uncertain significance (Nov 26, 2024)
4-67622858-G-A		not specified	Uncertain significance (Mar 04, 2024)
4-67622918-T-C		not specified	Uncertain significance (Oct 06, 2023)
4-67623181-T-C		not specified	Uncertain significance (Dec 21, 2023)
4-67624131-T-G		not specified	Uncertain significance (Jan 23, 2023)
4-67624153-G-C		not specified	Uncertain significance (May 25, 2022)
4-67624201-T-C		not specified	Uncertain significance (Jul 30, 2024)
4-67624216-G-C		not specified	Uncertain significance (Jul 20, 2022)
4-67625065-A-T		not specified	Uncertain significance (Aug 02, 2021)
4-67625067-C-T		not specified	Uncertain significance (Nov 12, 2024)
4-67625094-T-C		not specified	Uncertain significance (Oct 12, 2022)
4-67626390-T-C		not specified	Uncertain significance (Sep 11, 2024)
4-67626407-G-A		not specified	Uncertain significance (Feb 21, 2024)
4-67626458-G-A		not specified	Uncertain significance (Oct 10, 2023)
4-67629075-T-C		not specified	Uncertain significance (Dec 28, 2023)
4-67629082-G-A		not specified	Uncertain significance (Mar 01, 2023)
4-67630516-T-G		not specified	Uncertain significance (Jan 16, 2024)
4-67630533-T-G		not specified	Uncertain significance (Dec 20, 2023)
4-67631711-G-T		not specified	Uncertain significance (Apr 20, 2023)
4-67631859-C-T		not specified	Uncertain significance (May 17, 2023)
4-67631871-C-T		not specified	Uncertain significance (Jun 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UBA6	protein_coding	protein_coding	ENST00000322244	33	88528

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.73e-9	1.00	125659	0	89	125748	0.000354

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.10	461	532	0.866	0.0000257	6928
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00112	0.00110
Ashkenazi Jewish	0.000519	0.000496
East Asian	0.000554	0.000544
Finnish	0.000189	0.000185
European (Non-Finnish)	0.000370	0.000360
Middle Eastern	0.000554	0.000544
South Asian	0.000186	0.000163
Other	0.000661	0.000652

dbNSFP

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}.
• Pathway: 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;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;Protein ubiquitination (Consensus)

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.658
• rvis_EVS: -0.97
• rvis_percentile_EVS: 8.9

Haploinsufficiency Scores

• pHI: 0.414
• hipred: Y
• hipred_score: 0.652
• ghis: 0.658

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.665

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Uba6
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;learning;locomotory behavior;protein ubiquitination;amygdala development;hippocampus development;protein modification by small protein conjugation;dendritic spine development
• Cellular component: cytoplasm;cytosol
• Molecular function: ubiquitin activating enzyme activity;protein binding;ATP binding;FAT10 activating enzyme activity