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 cytosol and nucleoplasm. Predicted to be part of 90S preribosome. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.12

LOEUF

—

Mechanism

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

Background carrier burden — how many people carry a rare variant somewhere in TSR1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 42

1,057 rare PASS variants

Rare truncating (LoF)

1 in 640

194 rare PASS variants

Rare synonymous (reference)

1 in 170

395 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TSR1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 61	1 in 660
South Asian	~43k	1 in 47	1 in 650
Remaining (unassigned)	~30k	1 in 42	1 in 970
European (Finnish)	~27k	1 in 130	1 in 580
Admixed American	~22k	1 in 53	1 in 640
African / African American	~21k	1 in 45	1 in 510
East Asian	~20k	1 in 76	1 in 380
Ashkenazi Jewish	~13k	1 in 160	1 in 870
Middle Eastern	~2,884	1 in 48	≈ 1 in 850

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 15 coding exons well covered in gnomAD exomes and genomes.? see exons ↓