POLR3E

Chr 16

RNA polymerase III subunit E

Also known as: C37, RPC5, SIN

NCBI Gene: 55718 ENSG00000058600 UniProt: Q9NVU0 OMIM: 617815

The protein is a component of RNA polymerase III that synthesizes small non-coding RNAs including tRNAs, 5S rRNA, and snRNAs, and also functions as a DNA sensor in innate immune responses. Mutations cause hypomyelinating leukodystrophy, which follows autosomal recessive inheritance and typically presents in infancy or early childhood with developmental delays and progressive neurological deterioration. The gene is highly constrained against loss-of-function variants (LOEUF 0.453), reflecting its essential cellular functions.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in DNA-templated transcription; defense response to virus; and innate immune response. Located in nucleoplasm. Part of RNA polymerase III complex. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

LOEUF 0.45

Clinical Summary— POLR3E

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.

📋

ClinVar Variants

109 VUS of 136 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — POLR3E

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.013

Z-score 4.37

OE 0.28 (0.18–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.54Z-score

OE missense 0.80 (0.73–0.87)

364 obs / 456.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.28 (0.18–0.45)

0≤0.351.4

Missense OE?0.80 (0.73–0.87)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 12 / 42.9Missense obs/exp: 364 / 456.6Syn Z: -1.84

ClinVar Variant Classifications

136 submitted variants in ClinVar

ClinVar

Classification Summary

VUS109

Likely Benign5

Benign1

109

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	109	0	109
Likely Benign	4	1	5
Benign	1	0	1
Total	114	1	115

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

View in ClinVar →

70 pathogenic / likely-pathogenic (of 129) ClinVar copy-number / structural variants overlap POLR3E — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →