TSEN2

tRNA splicing endonuclease subunit 2, the group of tRNA-splicing endonuclease subunits

Basic information

Region (hg38): 3:12484421-12541549

Links

ENSG00000154743 ∙ NCBI:80746 ∙ OMIM:608753 ∙ HGNC:28422 ∙ Uniprot:Q8NCE0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pontocerebellar hypoplasia type 2B (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 2B (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 2 (Supportive), mode of inheritance: AR
• pontocerebellar hypoplasia type 2B (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pontocerebellar hypoplasia type 2B	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	18711368; 23562994

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TSEN2 gene.

• not_provided (148 variants)
• Inborn_genetic_diseases (68 variants)
• Pontoneocerebellar_hypoplasia (49 variants)
• not_specified (39 variants)
• Pontocerebellar_hypoplasia_type_2B (32 variants)
• TSEN2-related_disorder (10 variants)
• Hemolytic-uremic_syndrome (1 variants)
• Congenital_contractures_of_the_limbs_and_face,_hypotonia,_and_developmental_delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TSEN2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000025265.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	39	6	48
missense	2	4	109	8	2	125
nonsense	2	5	1			8
start loss						0
frameshift	2	3	2			7
splice donor/acceptor (+/-2bp)		2	2		1	5
Total	6	14	117	47	9

Highest pathogenic variant AF is 0.0000501863

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TSEN2	protein_coding	protein_coding	ENST00000284995	11	55192

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.01e-11	0.283	125681	0	67	125748	0.000266

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.999	308	262	1.17	0.0000144	3057
Missense in Polyphen		70	69.018	1.0142		867
Synonymous	-0.338	99	94.8	1.04	0.00000557	866
Loss of Function	0.995	20	25.4	0.787	0.00000132	310

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000177	0.000177
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000232	0.000231
European (Non-Finnish)	0.000346	0.000343
Middle Eastern	0.000109	0.000109
South Asian	0.000425	0.000425
Other	0.000497	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Constitutes one of the two catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5'- and 3'-splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3'-cyclic phosphate and 5'-OH termini. There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body. Isoform 1 probably carries the active site for 5'-splice site cleavage. The tRNA splicing endonuclease is also involved in mRNA processing via its association with pre- mRNA 3'-end processing factors, establishing a link between pre- tRNA splicing and pre-mRNA 3'-end formation, suggesting that the endonuclease subunits function in multiple RNA-processing events. Isoform 2 is responsible for processing a yet unknown RNA substrate. The complex containing isoform 2 is not able to cleave pre-tRNAs properly, although it retains endonucleolytic activity. {ECO:0000269|PubMed:15109492}.
• Pathway: tRNA processing;Metabolism of RNA;tRNA processing in the nucleus;tRNA splicing (Consensus)

Recessive Scores

• pRec: 0.0879

Intolerance Scores

• loftool: 0.938
• rvis_EVS: -0.75
• rvis_percentile_EVS: 13.67

Haploinsufficiency Scores

• pHI: 0.0927
• hipred: N
• hipred_score: 0.378
• ghis: 0.587

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.904

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tsen2

Gene ontology

• Biological process: tRNA-type intron splice site recognition and cleavage;tRNA splicing, via endonucleolytic cleavage and ligation;mRNA processing;RNA phosphodiester bond hydrolysis, endonucleolytic
• Cellular component: tRNA-intron endonuclease complex;nucleoplasm;nucleolus;centrosome;cytosol
• Molecular function: tRNA-intron endonuclease activity;nucleic acid binding;protein binding;lyase activity