RRN3

Chr 16

RNA polymerase I transcription factor RRN3

Also known as: A-270G1.2, TIFIA

NCBI Gene: 54700 ENSG00000085721 OMIM: 605121

The RRN3 protein is required for efficient transcription initiation by RNA polymerase I and formation of the competent pre-initiation complex in the nucleolus. Mutations cause autosomal recessive developmental delays, intellectual disability, and growth retardation with onset in infancy or early childhood. This gene is highly constrained against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA polymerase I core promoter sequence-specific DNA binding activity and RNA polymerase I general transcription initiation factor activity. Involved in transcription initiation at RNA polymerase I promoter. Located in nucleolus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.65

Clinical Summary— RRN3

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Population Constraint (gnomAD)

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

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ClinVar Variants

103 VUS of 126 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.65LOEUF

pLI 0.000

Z-score 3.15

OE 0.41 (0.27–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.77Z-score

OE missense 1.12 (1.03–1.22)

381 obs / 341.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.41 (0.27–0.65)

0≤0.351.4

Missense OE?1.12 (1.03–1.22)

0≤0.61.4

Synonymous OE?1.26

0≤1.21.6

LoF obs/exp: 14 / 33.8Missense obs/exp: 381 / 341.0Syn Z: -2.32

ClinVar Variant Classifications

126 submitted variants in ClinVar

ClinVar

Classification Summary

VUS103

Likely Benign6

Benign1

103

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	103	0	103
Likely Benign	4	2	6
Benign	1	0	1
Total	108	2	110

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

View in ClinVar →

118 pathogenic / likely-pathogenic (of 207) ClinVar copy-number / structural variants overlap RRN3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →