UBE2T

protein-coding

ubiquitin conjugating enzyme E2 T, the group of FA complementation groups|Ubiquitin conjugating enzymes E2

Gene summary

The protein encoded by this gene catalyzes the covalent attachment of ubiquitin to protein substrates. Defects in this gene have been associated with Fanconi anemia of complementation group T. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]

MANE transcript

NM_014176.4

Inheritance

ClinVar variants

P:9U:25B:17

Top phenotype

Fanconi anemia, complementation group T

gnomAD constraint

pLI —, LoF o/e 0.75

Max pathogenic AF

—

Genomic locus

chr1:202,331,544-202,341,984

External References & Databases

Ensembl (ENSG00000077152)

Transcript & Mutation Effects

hg38 • Region Span ~10.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Fanconi anemia complementation group TSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014638

Submitter: PanelApp Australia

Fanconi anemiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019391

Submitter: Orphanet

Fanconi anemia complementation group TSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014638

Submitter: Labcorp Genetics (formerly Invitae)

Fanconi anemia complementation group TSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014638

Submitter: G2P

Clinical Genomic Database (CGD)

Fanconi anemia, complementation group TAR

Manifestation: Cardiovascular; Hematologic; Musculoskeletal; Neurologic; Oncologic

Intervention: Cardiovascular; Hematologic; Oncologic

Rationale: In Fanconi anemia, specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended; Fanconi anemia can involve congenital cardiac (and other) anomalies, and awareness may allow early management

Refs: 20301575; 26046368

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to UBE2T variants in ClinVar

3 Conditions Cataloged

not providedTotal: 53

not specifiedTotal: 15

Fanconi anemia complementation group TTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014176.4. 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				16 clinvar		16
missense	1 clinvar		24 clinvar	1 clinvar		26
nonsense	2 clinvar					2
start loss						0
frameshift	3 clinvar	1 clinvar	1 clinvar			5
splice donor/acceptor (+/-2bp)		2 clinvar				2
Total	6	3	25	17	0	51

Highest pathogenic variant AF is 0.00001797246

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014176.4	RefSeq	NP_054895.1	6	MANE Select
ENST00000646651.1	Ensembl	ENSP00000494957.1	6	MANE Select
NM_001310326.2	RefSeq	NP_001297255.1	6	Standard
ENST00000643045.1	Ensembl	ENSP00000496572.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fanconi anemia pathway - Homo sapiens (human)
Gastric Cancer Network 2
Fanconi Anemia Pathway
DNA Repair
Post-translational protein modification

Biological Process

DNA repair
protein monoubiquitination
cellular response to DNA damage stimulus
protein ubiquitination
protein K29-linked ubiquitination

Molecular Function

chromatin binding
ubiquitin-protein transferase activity
protein binding
ATP binding
ubiquitin protein ligase binding

Cellular Component

nucleus
nucleoplasm
nucleolus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367274
Coding exons: 6
Length: 10324
Individuals with no LoFs: 125715
Homozygous LoFs: 0
Heterozygous LoFs: 31
Defined: 125746
p: 0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.316	96	105	0.913	0.00000495	1292
Missense (PolyPhen)		39	46.792	0.83348		562
Synonymous	0.486	32	35.7	0.897	0.00000168	366
Loss of Function	0.809	9	12.0	0.748	8.44e-7	115

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00065	0.00065	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes monoubiquitination. Involved in mitomycin-C (MMC)-induced DNA repair. Acts as a specific E2 ubiquitin-conjugating enzyme for the Fanconi anemia complex by associating with E3 ubiquitin-protein ligase FANCL and catalyzing monoubiquitination of FANCD2, a key step in the DNA damage pathway (PubMed:16916645, PubMed:17938197, PubMed:19111657, PubMed:19589784, PubMed:28437106). Also mediates monoubiquitination of FANCL and FANCI (PubMed:16916645, PubMed:17938197, PubMed:19111657, PubMed:19589784). May contribute to ubiquitination and degradation of BRCA1 (PubMed:19887602). In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, but may prefer 'Lys-11'-, 'Lys-27'-, 'Lys-48'- and 'Lys- 63'-linked polyubiquitination (PubMed:20061386). {ECO:0000269|PubMed:16916645, ECO:0000269|PubMed:17938197, ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:19589784, ECO:0000269|PubMed:19887602, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:28437106}.;
Disease: DISEASE: Fanconi anemia complementation group T (FANCT) [MIM:616435]: A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. {ECO:0000269|PubMed:26046368}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.0486

Intolerance Scores

LoFtool: 0.774
RVIS EVS: -0.12
RVIS percentile EVS: 44.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.621

Gene Damage Prediction

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