UBA5

ubiquitin like modifier activating enzyme 5, the group of Ubiquitin like modifier activating enzymes

Basic information

Region (hg38): 3:132654446-132679794

Previous symbols: [ "UBE1DC1" ]

Links

ENSG00000081307 ∙ NCBI:79876 ∙ OMIM:610552 ∙ HGNC:23230 ∙ Uniprot:Q9GZZ9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 44 (Strong), mode of inheritance: AR
• spinocerebellar ataxia, autosomal recessive 24 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 44; Spinocerebellar ataxia, autosomal recessive 24	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	26872069; 27545674; 27545681

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UBA5 gene.

• not provided (8 variants)
• Developmental and epileptic encephalopathy, 44 (6 variants)
• Early infantile epileptic encephalopathy with suppression bursts (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 UBA5 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				50		50
missense	2	5	76	2	1	86
nonsense	1	4				5
start loss	1					1
frameshift	9	1				10
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	2				3
splice region		1	4	5		10
non coding			4	45	2	51
Total	14	12	81	97	3

Highest pathogenic variant AF is 0.00000658

Variants in UBA5

This is a list of pathogenic ClinVar variants found in the UBA5 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-132659702-T-G			Uncertain significance (Nov 11, 2013)
3-132659706-G-A		not specified	Uncertain significance (Feb 11, 2022)
3-132659715-C-A		Developmental and epileptic encephalopathy, 44	Pathogenic (Apr 18, 2019)
3-132659724-C-T		not specified	Likely benign (Dec 07, 2021)
3-132660504-C-T			Likely benign (Dec 01, 2023)
3-132660529-G-A		UBA5-related disorder	Likely benign (Jan 04, 2023)
3-132660538-A-G		Developmental and epileptic encephalopathy, 44	Pathogenic (May 04, 2022)
3-132660541-G-A			Uncertain significance (Jul 22, 2021)
3-132660542-C-T			Uncertain significance (Mar 18, 2021)
3-132660543-G-A			Likely benign (Jul 12, 2022)
3-132660547-T-C			Uncertain significance (Jul 05, 2022)
3-132660557-G-A			Likely benign (Dec 13, 2023)
3-132660558-C-T			Likely benign (Oct 03, 2023)
3-132660572-TCC-T		Developmental and epileptic encephalopathy, 44	Pathogenic (May 04, 2022)
3-132660577-G-A			Uncertain significance (Jan 19, 2021)
3-132660600-G-A			Likely benign (Jun 18, 2023)
3-132660613-C-G			Uncertain significance (Jun 11, 2022)
3-132660621-G-A			Likely benign (Nov 27, 2023)
3-132660626-GC-G			Pathogenic (Apr 28, 2022)
3-132660628-G-T		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
3-132660644-G-A			Uncertain significance (Dec 11, 2020)
3-132660647-G-A			Uncertain significance (Feb 20, 2022)
3-132660652-C-T		Inborn genetic diseases	Uncertain significance (Mar 29, 2023)
3-132660665-T-TGG		Inborn genetic diseases • UBA5-related disorder	Pathogenic (Jun 13, 2019)
3-132660668-G-C			Uncertain significance (Jul 02, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UBA5	protein_coding	protein_coding	ENST00000356232	12	23652

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000252	0.997	125707	0	16	125723	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.29	158	211	0.750	0.00000988	2659
Missense in Polyphen		24	51.682	0.46438		630
Synonymous	1.52	54	70.2	0.769	0.00000331	749
Loss of Function	2.58	10	23.5	0.426	0.00000126	277

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000117	0.000117
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000444	0.0000440
Middle Eastern	0.000218	0.000217
South Asian	0.0000656	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E1-like enzyme which activates UFM1 and SUMO2. {ECO:0000269|PubMed:15071506, ECO:0000269|PubMed:18442052, ECO:0000269|PubMed:20368332, ECO:0000269|PubMed:27545674, ECO:0000269|PubMed:27545681}.
• Disease: DISEASE: Spinocerebellar ataxia, autosomal recessive, 24 (SCAR24) [MIM:617133]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR24 patients manifest gait instability and speech difficulties with onset in childhood. Clinical features include gait and limb ataxia, dysarthria, nystagmus, cataracts, and cerebellar atrophy on brain imaging. {ECO:0000269|PubMed:26872069}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: protein ubiquitylation;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

• pRec: 0.0887

Intolerance Scores

• loftool: 0.418
• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.56

Haploinsufficiency Scores

• pHI: 0.0632
• hipred: Y
• hipred_score: 0.629
• ghis: 0.516

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.735

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Uba5
• Phenotype: 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)

Zebrafish Information Network

• Gene name: uba5
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased mobility

Gene ontology

• Biological process: protein modification by small protein conjugation;regulation of intracellular estrogen receptor signaling pathway;response to endoplasmic reticulum stress;neuromuscular process;protein ufmylation;protein K69-linked ufmylation
• Cellular component: nucleus;cytoplasm;Golgi apparatus;cytosol;intracellular membrane-bounded organelle
• Molecular function: protein binding;ATP binding;metal ion binding;UFM1 activating enzyme activity