TSR1

Chr 17

TSR1 ribosome maturation factor

NCBI Gene: 55720 ENSG00000167721 UniProt: Q2NL82 OMIM: 611214

The TSR1 protein is required for maturation of the 40S ribosomal subunit in the nucleolus through RNA binding and processing of ribosomal RNA transcripts. Mutations cause autosomal recessive intellectual disability with congenital malformations and dysmorphic facies, typically presenting in early infancy with developmental delays and distinctive facial features. This gene is highly intolerant to loss-of-function variants, reflecting its essential role in ribosome biogenesis.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA binding activity. Predicted to be involved in endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) and maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be located in nucleolus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 1.12

Clinical Summary— TSR1

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

157 VUS of 192 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.12LOEUF

pLI 0.000

Z-score 0.92

OE 0.85 (0.64–1.12)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.06Z-score

OE missense 1.01 (0.93–1.09)

445 obs / 441.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.85 (0.64–1.12)

0≤0.351.4

Missense OE?1.01 (0.93–1.09)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 35 / 41.4Missense obs/exp: 445 / 441.2Syn Z: -0.33

ClinVar Variant Classifications

192 submitted variants in ClinVar

ClinVar

Classification Summary

VUS157

Likely Benign7

Benign4

157

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	156	0	0	157
Likely Benign	0	6	1	0	7
Benign	0	2	1	1	4
Total	1	164	2	1	168

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

View in ClinVar →

59 pathogenic / likely-pathogenic (of 76) ClinVar copy-number / structural variants overlap TSR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →