TSEN54

Chr 17AR

tRNA splicing endonuclease subunit 54

Also known as: PCH2A, PCH4, PCH5, SEN54L, sen54

This gene encodes a subunit of the tRNA splicing endonuclease complex that catalyzes intron removal from precursor tRNAs and is involved in pre-mRNA 3-prime end processing. Mutations cause pontocerebellar hypoplasia types 2A, 4, and 5 through autosomal recessive inheritance. The pathogenic mechanism involves disrupted tRNA processing leading to defective protein synthesis.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

?Pontocerebellar hypoplasia type 5MIM #610204
AR
Pontocerebellar hypoplasia type 2AMIM #277470
AR
Pontocerebellar hypoplasia type 4MIM #225753
AR
0
Active trials
6
Pubs (1 yr)
183
P/LP submissions
9%
P/LP missense
0.88
LOEUF
LOF
Mechanism· G2P
Clinical SummaryTSEN54
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
99 unique Pathogenic / Likely Pathogenic· 239 VUS of 749 total submissions
📖
GeneReview available — TSEN54
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.88LOEUF
pLI 0.000
Z-score 2.03
OE 0.57 (0.380.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.07Z-score
OE missense 1.01 (0.921.11)
299 obs / 295.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.57 (0.380.88)
00.351.4
Missense OE1.01 (0.921.11)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 15 / 26.2Missense obs/exp: 299 / 295.4Syn Z: -0.76

ClinVar Variant Classifications

749 submitted variants in ClinVar

Classification Summary

Pathogenic64
Likely Pathogenic35
VUS239
Likely Benign318
Benign44
Conflicting35
64
Pathogenic
35
Likely Pathogenic
239
VUS
318
Likely Benign
44
Benign
35
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
29
2
33
0
64
Likely Pathogenic
19
7
8
1
35
VUS
2
203
31
3
239
Likely Benign
0
18
137
163
318
Benign
0
10
31
3
44
Conflicting
35
Total50240240170735

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TSEN54 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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