GeneBe

TSEN2

protein-coding

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

Gene summary

This gene encodes one of the subunits of the tRNA splicing endonuclease. This endonuclease catalyzes the first step in RNA splicing which is the removal of introns. Mutations in this gene have been associated with pontocerebellar hypoplasia type 2. A pseudogene has been identified on chromosome 4. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2009]

MANE transcript

NM_025265.4

Inheritance

AR

ClinVar variants

P:27U:128B:67

Top phenotype

Pontocerebellar hypoplasia type 2B

gnomAD constraint

pLI —, LoF o/e 0.79

Max pathogenic AF

—

Genomic locus

chr3:12,484,421-12,541,549

External References & Databases

Ensembl (ENSG00000154743)NCBI Gene (80746)OMIM (608753)HGNC:28422GenCCUniProt (Q8NCE0)AlphaFoldClinVar (TSEN2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~57.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pontocerebellar hypoplasia type 2SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016759

Submitter: Orphanet

pontocerebellar hypoplasia type 2BSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012890

Submitter: G2P

pontocerebellar hypoplasia type 2BSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012890

Submitter: PanelApp Australia

pontocerebellar hypoplasia type 2BSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012890

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Pontocerebellar hypoplasia type 2BAR

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 18711368; 23562994Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TSEN2 variants in ClinVar

8 Conditions Cataloged
not providedTotal: 179
Inborn genetic diseasesTotal: 76
Pontoneocerebellar hypoplasiaTotal: 46
not specifiedTotal: 46
Pontocerebellar hypoplasia type 2BTotal: 35
TSEN2-related disorderTotal: 11
Hemolytic-uremic syndromeTotal: 1
Congenital contractures of the limbs and face, hypotonia, and developmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025265.4. 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
49
clinvar
6
clinvar
 58
missense
1
clinvar
4
clinvar
120
clinvar
9
clinvar
2
clinvar
 136
nonsense
4
clinvar
5
clinvar
1
clinvar
 10
start loss
1
clinvar
 1
frameshift
4
clinvar
4
clinvar
1
clinvar
 9
splice donor/acceptor (+/-2bp)
5
clinvar
2
clinvar
1
clinvar
 8
Total918128589222

Highest pathogenic variant AF is 0.00005018631

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 157 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_025265.4RefSeqNP_079541.111MANE Select
ENST00000284995.11EnsemblENSP00000284995.611MANE Select
NM_001145392.2RefSeqNP_001138864.111Standard
NM_001145393.3RefSeqNP_001138865.110Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • tRNA processing
  • Metabolism of RNA
  • tRNA processing in the nucleus
  • tRNA splicing

Biological Process

  • tRNA-type intron splice site recognition and cleavage
  • tRNA splicing, via endonucleolytic cleavage and ligation
  • mRNA processing
  • RNA phosphodiester bond hydrolysis, endonucleolytic

Molecular Function

  • tRNA-intron endonuclease activity
  • nucleic acid binding
  • protein binding
  • lyase activity

Cellular Component

  • tRNA-intron endonuclease complex
  • nucleoplasm
  • nucleolus
  • centrosome
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000284995
Coding exons
11
Length
55192
Individuals with no LoFs
125681
Homozygous LoFs
0
Heterozygous LoFs
67
Defined
125748
p
0.000266
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.9993082621.170.00001443057
Missense (PolyPhen)7069.0181.0142867
Synonymous-0.3389994.81.040.00000557866
Loss of Function0.9952025.40.7870.00000132310

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.000120.00012rare
Ashkenazi Jewish00.0absent
East Asian0.000110.00011rare
Finnish0.000230.00023rare
European (Non-Finnish)0.000350.00034rare
South Asian0.000420.00042rare
Other0.000500.00049rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec
0.0879

Intolerance Scores

LoFtool
0.938
RVIS EVS
-0.75
RVIS percentile EVS
13.67

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.904

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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