TSR3

Chr 16

TSR3 ribosome maturation factor

TSR3 encodes an aminocarboxypropyltransferase that catalyzes the final step in creating a hypermodified pseudouridine residue in 18S ribosomal RNA, essential for ribosome biogenesis. Mutations cause autosomal recessive intellectual disability with microcephaly and growth retardation, typically presenting in infancy with developmental delays and failure to thrive. This gene shows tolerance to loss-of-function variants in the general population, consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.15
Clinical SummaryTSR3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.15LOEUF
pLI 0.001
Z-score 1.25
OE 0.58 (0.321.15)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.50Z-score
OE missense 1.11 (0.981.25)
189 obs / 170.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.58 (0.321.15)
00.351.4
Missense OE1.11 (0.981.25)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 6 / 10.3Missense obs/exp: 189 / 170.6Syn Z: 0.39
DN
0.6552th %ile
GOF
0.4678th %ile
LOF
0.2387th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TSR3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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