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  3. TSEN34
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Fetal anomalies

Gene: TSEN34

Green List (high evidence)
TSEN34 (tRNA splicing endonuclease subunit 34)
EnsemblGeneIds (GRCh38): ENSG00000170892
EnsemblGeneIds (GRCh37): ENSG00000170892
OMIM: 608754, Gene2Phenotype
TSEN34 is in 11 panels

5 reviews

Ida Ertmanska (Genomics England Curator)

I don't know

Comment on list classification: There is one patient reported in literature with a biallelic variant in TSEN34 and Pontocerebellar hypoplasia type 2. While TSEN34 shares a biochemical function with other genes known to cause Pontocerebellar hypoplasia type 2, the clinical evidence for this gene-disease association is lacking in literature. Hence, TSEN34 should be demoted to Amber for Ataxia and cerebellar anomalies - narrow panel, until more evidence emerges.
Created: 31 Dec 2025, 10:56 a.m. | Last Modified: 31 Dec 2025, 10:56 a.m.
Panel Version: 6.129
PMID: 20952379 Namavar et al., 2011
Reported one Pontocerebellar hypoplasia type 2C patient with a homozygous p.R58W variant in TSEN34 and epileptic seizures. PCH2 patient with seizures and TSEN34 variant reported in (most likely the same patient as in PMID:18711368 Budde et al., 2008). Sequenced exon-intron boundaries of TSEN54, TSEN34, TSEN2, TSEN15, RARS2 and VRK1 only.
Patient details from PMID:18711368: Patient hg1, male, phenotype: progressive microcephaly, chorea/dystonia, visual impairment, spontaneous breath; MRI typical.


PMID: 27370523 Balbi, Taicher & Litman, 2016
Brief mention of a 2-year-old female child diagnosed with TSEN34-related pontocerebellar hypoplasia Type 2 - no variant/clinical details.

Functional evidence:
PMID: 32476018 Hayne et al., 2020 / PMID: 37544645 Hayne et al., 2023
Human tRNA splicing endonuclease (TSEN) is comprised of four core subunits (TSEN54, TSEN2, TSEN34 and TSEN15), and it co-purifies with CLP1. Other TSEN subunits and CLP1 are all known to cause PCH. The TSEN34 R58W mutation eliminates a salt bridge between R58 and E218, affecting protein stability.

Additional info:
Variant NM_001077446.4(TSEN34):c.862_865dup (p.Leu289fs) was reported as Likely Pathogenic for Pontocerebellar hypoplasia type 2C in ClinVar by Mendelics (source: clinical testing).

This gene is putatively linked to AR Pontocerebellar hypoplasia type 2C, MIM:612390 (OMIM accessed 15th Dec 2025).
Created: 31 Dec 2025, 10:56 a.m. | Last Modified: 31 Dec 2025, 10:56 a.m.
Panel Version: 6.129

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pontocerebellar hypoplasia type 2C, OMIM:612390; pontocerebellar hypoplasia type 2C, MONDO:0012891

Publications

Created: 31 Dec 2025, 10:56 a.m.
Last Modified: 31 Dec 2025, 10:56 a.m.
Panel version: 6.129

Arina Puzriakova (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 3 Mar 2022, 11:19 a.m. | Last Modified: 3 Mar 2022, 11:19 a.m.
Panel Version: 1.836
Created: 3 Mar 2022, 11:19 a.m.
Last Modified: 3 Mar 2022, 11:19 a.m.
Panel version: 1.836

Catherine Snow (Genomics England)

Comment on list classification: Gene reviewed by Rhiannon Mellis (GOSH). Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag)
Created: 1 Feb 2021, 5:29 p.m. | Last Modified: 1 Feb 2021, 5:29 p.m.
Panel Version: 1.590
Created: 1 Feb 2021, 5:29 p.m.
Last Modified: 1 Feb 2021, 5:29 p.m.
Panel version: 1.590

Rhiannon Mellis (Great Ormond Street Hospital)

Green List (high evidence)

This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel (Cerebellar hypoplasia). Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Created: 28 Jan 2021, 11:03 a.m. | Last Modified: 28 Jan 2021, 11:03 a.m.
Panel Version: 1.185

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pontocerebellar hypoplasia type 2C

Created: 28 Jan 2021, 11:03 a.m.
Last Modified: 28 Jan 2021, 11:03 a.m.
Panel version: 1.185

Rebecca Foulger (Genomics England curator)

I don't know

DDG2P rating in original PAGE list: Probable for PONTOCEREBELLAR HYPOPLASIA TYPE 2 AND TYPE 4
Created: 11 Dec 2018, 9:05 a.m.
In the original PAGE file, MOP listed as All missense/in frame.
Created: 8 Nov 2018, 4:45 p.m.

Mode of pathogenicity
Other - please provide details in the comments

Created: 8 Nov 2018, 4:45 p.m.

Panel version: 0.9

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • PAGE DD-Gene2Phenotype
Phenotypes
  • PONTOCEREBELLAR HYPOPLASIA TYPE 2 AND TYPE 4
Tags
Q4_25_demote_amber
OMIM
608754
Clinvar variants
Variants in TSEN34
Penetrance
None
Panels with this gene

History Filter Activity

31 Dec 2025, Gel status: 3

Added Tag

Ida Ertmanska (Genomics England Curator)

Tag Q4_25_demote_amber tag was added to gene: TSEN34.

3 Mar 2022, Gel status: 3

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review was removed from gene: TSEN34.

3 Mar 2022, Gel status: 3

Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source Expert Review Green was added to TSEN34. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

1 Feb 2021, Gel status: 2

Added Tag

Catherine Snow (Genomics England)

Tag for-review tag was added to gene: TSEN34.

1 Feb 2021, Gel status: 2

Entity classified by Genomics England curator

Catherine Snow (Genomics England)

Gene: tsen34 has been classified as Amber List (Moderate Evidence).

8 Nov 2018, Gel status: 2

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Rebecca Foulger (Genomics England curator)

gene: TSEN34 was added gene: TSEN34 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: TSEN34 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TSEN34 were set to PONTOCEREBELLAR HYPOPLASIA TYPE 2 AND TYPE 4