POLR3E

Chr 16

RNA polymerase III subunit E

Also known as: C37, RPC5, SIN

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.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
LOEUF 0.45
Clinical SummaryPOLR3E
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
70 unique Pathogenic / Likely Pathogenic· 155 VUS of 264 total submissions
📖
GeneReview available — POLR3E
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.013
Z-score 4.37
OE 0.28 (0.180.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.54Z-score
OE missense 0.80 (0.730.87)
364 obs / 456.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.28 (0.180.45)
00.351.4
Missense OE0.80 (0.730.87)
00.61.4
Synonymous OE1.17
01.21.6
LoF obs/exp: 12 / 42.9Missense obs/exp: 364 / 456.6Syn Z: -1.84

ClinVar Variant Classifications

264 submitted variants in ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic16
VUS155
Likely Benign9
Benign2
Conflicting4
54
Pathogenic
16
Likely Pathogenic
155
VUS
9
Likely Benign
2
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
54
0
54
Likely Pathogenic
0
0
16
0
16
VUS
0
109
46
0
155
Likely Benign
0
4
4
1
9
Benign
0
1
1
0
2
Conflicting
4
Total01141211240

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

View in ClinVar →

Protein Context — Lollipop Plot

POLR3E · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC