UBE2A

ubiquitin conjugating enzyme E2 A, the group of Ubiquitin conjugating enzymes E2

Basic information

Region (hg38): X:119474802-119591083

Links

ENSG00000077721 ∙ NCBI:7319 ∙ OMIM:312180 ∙ HGNC:12472 ∙ Uniprot:P49459 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic X-linked intellectual disability Nascimento type (Strong), mode of inheritance: XL
• syndromic X-linked intellectual disability Nascimento type (Definitive), mode of inheritance: XLR
• syndromic X-linked intellectual disability Nascimento type (Supportive), mode of inheritance: XL
• syndromic X-linked intellectual disability Nascimento type (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked, syndromic, Nascimento-type	XL	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	Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Neurologic	16909393; 20339384; 20412111; 21108393

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UBE2A gene.

• not provided (3 variants)
• Intellectual disability, X-linked 107 (1 variants)
• Inborn genetic diseases (1 variants)
• Syndromic X-linked intellectual disability Nascimento type (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UBE2A 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	9		10
missense	2	1	18			21
nonsense	1	1				2
start loss		2				2
frameshift		1	1			2
inframe indel		2				2
splice donor/acceptor (+/-2bp)	1	3				4
splice region			1	2	1	4
non coding	1	2	11	3	4	21
Total	5	12	31	12	4

Variants in UBE2A

This is a list of pathogenic ClinVar variants found in the UBE2A region.

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

Position	Type	Phenotype	Significance	ClinVar
X-119539766-C-T			Likely benign (Jul 01, 2024)
X-119541336-G-A		Intellectual disability, X-linked 107	Pathogenic (-)
X-119541341-C-T		Intellectual disability, X-linked 107	Uncertain significance (Jul 17, 2023)
X-119542509-T-G			Uncertain significance (Jul 14, 2020)
X-119542514-CTCCTCT-C		Intellectual disability, X-linked 107	Pathogenic (Feb 05, 2020)
X-119542524-T-C		Intellectual disability, X-linked 107	Uncertain significance (Nov 24, 2023)
X-119542533-A-G			Uncertain significance (Mar 27, 2019)
X-119544385-T-C			Uncertain significance (Mar 22, 2022)
X-119544401-G-A		Intellectual disability, X-linked 107	Benign (Jul 30, 2021)
X-119544416-G-C			Likely benign (Jul 01, 2024)
X-119544421-C-T			Uncertain significance (Jun 14, 2023)
X-119544489-C-T		Intellectual disability, X-linked 107	Uncertain significance (Dec 21, 2023)
X-119545508-C-T			Uncertain significance (Nov 01, 2023)
X-119560279-CAT-C		Intellectual disability, X-linked 107	Uncertain significance (Aug 24, 2022)
X-119560341-G-C		Intellectual disability, X-linked 107	Uncertain significance (Dec 12, 2018)
X-119560346-C-T			Uncertain significance (May 22, 2024)
X-119560346-CG-C		Intellectual disability, X-linked 107	Likely pathogenic (May 23, 2022)
X-119560350-C-CTA		Intellectual disability, X-linked 107	Pathogenic (Sep 25, 2024)
X-119560352-C-A		Intellectual disability, X-linked 107	Uncertain significance (Sep 26, 2019)
X-119565276-AG-A		Intellectual disability, X-linked 107	Likely pathogenic (Jul 26, 2023)
X-119565312-C-A		Intellectual disability, X-linked 107	Uncertain significance (Mar 12, 2020)
X-119565357-A-G		Intellectual disability, X-linked 107	Benign (Jul 30, 2021)
X-119574593-C-T			Likely benign (Oct 01, 2024)
X-119574635-C-T			Uncertain significance (Jul 01, 2023)
X-119574708-C-T		Inborn genetic diseases	Uncertain significance (Mar 31, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UBE2A	protein_coding	protein_coding	ENST00000371558	6	9881

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.815	0.181	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.46	8	63.0	0.127	0.00000468	1005
Missense in Polyphen		2	25.935	0.077116		460
Synonymous	0.384	18	20.2	0.891	0.00000131	282
Loss of Function	2.19	0	5.57	0.00	3.53e-7	95

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
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: Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In association with the E3 enzyme BRE1 (RNF20 and/or RNF40), it plays a role in transcription regulation by catalyzing the monoubiquitination of histone H2B at 'Lys-120' to form H2BK120ub1. H2BK120ub1 gives a specific tag for epigenetic transcriptional activation, elongation by RNA polymerase II, telomeric silencing, and is also a prerequisite for H3K4me and H3K79me formation. In vitro catalyzes 'Lys-11', as well as 'Lys-48'-linked polyubiquitination. Required for postreplication repair of UV-damaged DNA. {ECO:0000269|PubMed:16337599, ECO:0000269|PubMed:20061386}.
• Disease: DISEASE: Mental retardation, X-linked, syndromic, Nascimento-type (MRXSN) [MIM:300860]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSN features include dysmorphic facies, hirsutism, skin and nails abnormalities, obesity, speech anomalies and seizures. {ECO:0000269|PubMed:16909393, ECO:0000269|PubMed:20412111}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Ubiquitin mediated proteolysis - Homo sapiens (human);hypoxia-inducible factor in the cardivascular system;hypoxia and p53 in the cardiovascular system;tumor suppressor arf inhibits ribosomal biogenesis;proteasome complex;gamma-aminobutyric acid receptor life cycle pathway;fibrinolysis pathway;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;sumoylation as a mechanism to modulate ctbp-dependent gene responses;Protein ubiquitination;E3 ubiquitin ligases ubiquitinate target proteins (Consensus)

Recessive Scores

• pRec: 0.130

Intolerance Scores

• rvis_EVS: 0.15
• rvis_percentile_EVS: 63.81

Haploinsufficiency Scores

• pHI: 0.879
• hipred: Y
• hipred_score: 0.800
• ghis: 0.637

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Mouse Genome Informatics

• Gene name: Ube2a
• Phenotype: growth/size/body region 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system 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)

Gene ontology

• Biological process: protein polyubiquitination;blastocyst hatching;DNA repair;postreplication repair;ubiquitin-dependent protein catabolic process;positive regulation of cell population proliferation;response to UV;protein ubiquitination;histone H2A ubiquitination;proteasome-mediated ubiquitin-dependent protein catabolic process;protein autoubiquitination;maternal process involved in female pregnancy;protein K48-linked ubiquitination;protein K11-linked ubiquitination
• Cellular component: chromatin;nuclear chromatin;XY body;nucleoplasm;cytosol;HULC complex
• Molecular function: ubiquitin-protein transferase activity;protein binding;ATP binding;ubiquitin protein ligase binding;ubiquitin binding;ubiquitin conjugating enzyme activity