UBA2

ubiquitin like modifier activating enzyme 2, the group of Ubiquitin like modifier activating enzymes

Basic information

Region (hg38): 19:34428351-34471251

Previous symbols: [ "SAE2" ]

Links

ENSG00000126261 ∙ NCBI:10054 ∙ OMIM:613295 ∙ HGNC:30661 ∙ Uniprot:Q9UBT2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• multiple congenital anomalies/dysmorphic syndrome (Strong), mode of inheritance: AD
• ACCES syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
ACCES syndrome	AD	Cardiovascular	The condition can include congenital cardiac anomalies, and awareness may allow early identification and management	Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Renal	34040189

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UBA2 gene.

• ACCES syndrome (4 variants)
• not provided (3 variants)
• UBA2-related disorder (1 variants)
• Chromosome 19q13.11 deletion syndrome, distal (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UBA2 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				1		1
missense		3	29			32
nonsense	2					2
start loss		1				1
frameshift	3	2				5
inframe indel						0
splice donor/acceptor (+/-2bp)	2		1			3
splice region				1		1
non coding					1	1
Total	7	6	30	1	1

Variants in UBA2

This is a list of pathogenic ClinVar variants found in the UBA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-34428433-A-G		Inborn genetic diseases	Likely pathogenic (Nov 13, 2018)
19-34428443-C-G		Inborn genetic diseases	Uncertain significance (Mar 07, 2024)
19-34428445-CG-C		ACCES syndrome	Pathogenic (-)
19-34428463-C-A		Inborn genetic diseases	Uncertain significance (Dec 21, 2022)
19-34428472-G-A		Inborn genetic diseases	Uncertain significance (Dec 20, 2022)
19-34428476-TGGCCGGG-T		Inborn genetic diseases	Likely pathogenic (Apr 03, 2023)
19-34428476-T-TGGCCGGG			Pathogenic (Aug 10, 2020)
19-34428503-G-T		ACCES syndrome	Likely pathogenic (Sep 09, 2020)
19-34428563-T-C		Inborn genetic diseases	Uncertain significance (Apr 12, 2024)
19-34430578-T-G		Inborn genetic diseases	Uncertain significance (Jan 23, 2023)
19-34430604-A-C			Likely pathogenic (Sep 09, 2020)
19-34430612-A-G		ACCES syndrome	Uncertain significance (Oct 02, 2023)
19-34431860-G-A			Uncertain significance (Aug 14, 2019)
19-34433348-C-T		Inborn genetic diseases	Likely benign (Jun 13, 2022)
19-34433378-GT-G		ACCES syndrome	Pathogenic (Jul 14, 2022)
19-34434870-G-A		Inborn genetic diseases	Uncertain significance (Dec 16, 2022)
19-34434873-C-G		Ectrodactyly • ACCES syndrome	Uncertain significance (Sep 29, 2020)
19-34434873-C-T		UBA2-related disorder • ACCES syndrome	Pathogenic (Jan 23, 2024)
19-34438643-A-G		ACCES syndrome	Pathogenic (Mar 25, 2024)
19-34438649-T-A			Uncertain significance (Apr 04, 2018)
19-34438657-T-C		ACCES syndrome	Uncertain significance (Jul 17, 2023)
19-34438685-A-G		Inborn genetic diseases	Uncertain significance (Sep 27, 2022)
19-34438697-C-T			Uncertain significance (Feb 11, 2022)
19-34443872-CA-C		ACCES syndrome	Pathogenic (Jul 14, 2022)
19-34443912-G-A		ACCES syndrome	Pathogenic (Mar 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UBA2	protein_coding	protein_coding	ENST00000246548	17	41597

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00149	122449	0	1	122450	0.00000408

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.61	190	322	0.591	0.0000166	4220
Missense in Polyphen		17	77.479	0.21941		1080
Synonymous	0.543	106	113	0.935	0.00000612	1182
Loss of Function	4.77	3	32.2	0.0932	0.00000152	427

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000308	0.0000308
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The heterodimer acts as an E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2. {ECO:0000269|PubMed:11451954, ECO:0000269|PubMed:11481243, ECO:0000269|PubMed:15660128, ECO:0000269|PubMed:17643372, ECO:0000269|PubMed:19443651, ECO:0000269|PubMed:20164921}.
• Pathway: Ubiquitin mediated proteolysis - Homo sapiens (human);SUMO is conjugated to E1 (UBA2:SAE1);SUMO is transferred from E1 to E2 (UBE2I, UBC9);Post-translational protein modification;basic mechanisms of sumoylation;Metabolism of proteins;Processing and activation of SUMO;SUMOylation (Consensus)

Recessive Scores

• pRec: 0.136

Intolerance Scores

• loftool: 0.0661
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.99

Haploinsufficiency Scores

• pHI: 0.952
• hipred: Y
• hipred_score: 0.831
• ghis: 0.637

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.815

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Uba2

Gene ontology

• Biological process: protein sumoylation;protein modification by small protein conjugation;positive regulation of catalytic activity
• Cellular component: nucleoplasm;cytoplasm;SUMO activating enzyme complex
• Molecular function: magnesium ion binding;protein binding;ATP binding;enzyme activator activity;transcription factor binding;transferase activity;acid-amino acid ligase activity;SUMO activating enzyme activity;SUMO binding;small protein activating enzyme binding;ubiquitin-like protein conjugating enzyme binding;protein heterodimerization activity