TSEN54

tRNA splicing endonuclease subunit 54, the group of tRNA-splicing endonuclease subunits

Basic information

Region (hg38): 17:75515943-75524735

Links

ENSG00000182173 ∙ NCBI:283989 ∙ OMIM:608755 ∙ HGNC:27561 ∙ Uniprot:Q7Z6J9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pontocerebellar hypoplasia type 2A (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 4 (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 2A (Definitive), mode of inheritance: AR
• pontocerebellar hypoplasia type 2 (Supportive), mode of inheritance: AR
• pontocerebellar hypoplasia type 4 (Supportive), mode of inheritance: AR
• pontocerebellar hypoplasia type 5 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pontocerebellar hypoplasia, type 2A; Pontocerebellar hypoplasia type 4; Pontocerebellar hypoplasia type 5	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	8480512; 16470708; 18711368; 20956791; 21368912

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TSEN54 gene.

• not provided (363 variants)
• Pontoneocerebellar hypoplasia (69 variants)
• not specified (54 variants)
• Inborn genetic diseases (39 variants)
• Pontocerebellar hypoplasia type 2A (19 variants)
• Pontocerebellar hypoplasia type 4 (19 variants)
• Pontocerebellar hypoplasia type 5 (13 variants)
• Olivopontocerebellar hypoplasia (9 variants)
• Pontocerebellar hypoplasia type 4;Pontocerebellar hypoplasia type 2A;Pontocerebellar hypoplasia type 5 (8 variants)
• Congenital cerebellar hypoplasia (1 variants)
• Microcephaly;Global developmental delay (1 variants)
• Pontocerebellar hypoplasia type 2A;Pontocerebellar hypoplasia type 4 (1 variants)
• Pontocerebellar hypoplasia type 4;Pontocerebellar hypoplasia type 2A (1 variants)
• TSEN54 Pontocerebellar Hypoplasia (1 variants)
• TSEN54-related condition (1 variants)
• Abnormality of the nervous system (1 variants)
• Pontocerebellar hypoplasia type 5;Pontocerebellar hypoplasia type 4;Methylmalonic aciduria and homocystinuria type cblD (1 variants)
• Intellectual disability (1 variants)
• Methylmalonic aciduria and homocystinuria type cblD;Pontocerebellar hypoplasia type 4;Pontocerebellar hypoplasia type 5 (1 variants)
• Amblyopia;Global developmental delay;Hypertonia (1 variants)
• Pontocerebellar hypoplasia type 5;Pontocerebellar hypoplasia type 2A;Pontocerebellar hypoplasia type 4 (1 variants)
• Pontocerebellar hypoplasia type 2A;Pontocerebellar hypoplasia type 5;Pontocerebellar hypoplasia type 4 (1 variants)
• Pontocerebellar hypoplasia type 2;Pontocerebellar hypoplasia type 4 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TSEN54 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	6	64	3	74
missense		5	167	10	10	192
nonsense	9	3				12
start loss	1	1				2
frameshift	19	5	1			25
inframe indel			6			6
splice donor/acceptor (+/-2bp)	2	4	1			7
splice region	1		13	15	1	30
non coding			6	41	24	71
Total	31	19	187	115	37

Highest pathogenic variant AF is 0.0000201

Variants in TSEN54

This is a list of pathogenic ClinVar variants found in the TSEN54 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-75516224-A-G			Benign (Jun 19, 2018)
17-75516273-A-C			Benign (Jun 14, 2018)
17-75516282-C-T			Benign (Jun 28, 2018)
17-75516305-C-T			Benign (Jun 28, 2018)
17-75516561-A-C		Olivopontocerebellar hypoplasia	Pathogenic (Feb 08, 2013)
17-75516562-T-C			Likely pathogenic (Mar 09, 2020)
17-75516562-T-TGGAGCC		not specified • Pontoneocerebellar hypoplasia • Pontocerebellar hypoplasia type 4	Conflicting classifications of pathogenicity (Feb 01, 2024)
17-75516563-G-GGAGCCC			Likely benign (Dec 03, 2023)
17-75516566-G-A			Likely benign (Jan 16, 2024)
17-75516566-G-C			Uncertain significance (May 04, 2022)
17-75516567-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 14, 2023)
17-75516566-G-GCCGGAT			Uncertain significance (Jun 03, 2016)
17-75516569-C-G			Likely benign (Dec 26, 2023)
17-75516572-G-A			Likely benign (Jan 08, 2024)
17-75516572-G-T		not specified • Pontoneocerebellar hypoplasia • Pontocerebellar hypoplasia type 5 • Pontocerebellar hypoplasia type 2A • Pontocerebellar hypoplasia type 4	Benign (Feb 01, 2024)
17-75516572-GC-TT			Uncertain significance (Jun 20, 2021)
17-75516573-C-T		Pontoneocerebellar hypoplasia	Uncertain significance (Aug 01, 2022)
17-75516575-C-A			Likely benign (Jan 04, 2024)
17-75516575-C-G			Likely benign (Dec 09, 2023)
17-75516575-C-T			Likely benign (Apr 25, 2023)
17-75516576-G-C		Pontoneocerebellar hypoplasia	Uncertain significance (Sep 01, 2022)
17-75516576-G-T			Pathogenic (Dec 05, 2023)
17-75516578-G-T			Likely benign (Jan 18, 2024)
17-75516580-C-T			Uncertain significance (Dec 02, 2021)
17-75516581-C-G			Likely benign (Apr 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TSEN54	protein_coding	protein_coding	ENST00000333213	11	8680

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.75e-7	0.966	125710	0	38	125748	0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0738	299	295	1.01	0.0000183	3334
Missense in Polyphen		96	93.415	1.0277		1113
Synonymous	-0.757	136	125	1.09	0.00000750	1049
Loss of Function	2.03	15	26.2	0.573	0.00000139	286

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000555	0.000544
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000143	0.000132
Middle Eastern	0.000109	0.000109
South Asian	0.000231	0.000229
Other	0.000337	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Non-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. 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. {ECO:0000269|PubMed:15109492}.
• Disease: DISEASE: Pontocerebellar hypoplasia 4 (PCH4) [MIM:225753]: A disorder characterized by an abnormally small cerebellum and brainstem, severe neonatal encephalopathy, microcephaly, myoclonus and muscular hypertonia. There is a severe inferior olivary and pontine neuronal loss and a diffuse white matter gliosis. {ECO:0000269|PubMed:18711368, ECO:0000269|PubMed:21824568}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Pontocerebellar hypoplasia 2A (PCH2A) [MIM:277470]: A disorder characterized by an abnormally small cerebellum and brainstem, and progressive microcephaly from birth combined with extrapyramidal dyskinesia. Severe chorea occurs and epilepsy is frequent. There are no signs of spinal cord anterior horn cells degeneration. {ECO:0000269|PubMed:18711368, ECO:0000269|PubMed:23307886}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Pontocerebellar hypoplasia 5 (PCH5) [MIM:610204]: A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum. Brain MRI shows an abnormally small cerebellum and brainstem, decreased cerebral white matter, and a thin corpus callosum. {ECO:0000269|PubMed:21368912}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: tRNA processing;Metabolism of RNA;tRNA processing in the nucleus;tRNA splicing (Consensus)

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.559
• rvis_EVS: 1.66
• rvis_percentile_EVS: 96.28

Haploinsufficiency Scores

• pHI: 0.131
• hipred: N
• hipred_score: 0.167
• ghis: 0.417

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.932

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Tsen54

Zebrafish Information Network

• Gene name: tsen54
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: dead

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
• Molecular function: tRNA-intron endonuclease activity;protein binding