POLR3D

Chr 8

RNA polymerase III subunit D

Also known as: BN51T, C53, RPC4, RPC53, TSBN51

The protein serves as a specific peripheral component of RNA polymerase III, which transcribes small non-coding RNAs including tRNAs, 5S rRNA, and microRNAs, and also functions as a DNA sensor in innate immune responses. Mutations cause autosomal recessive hypomyelinating leukodystrophy, typically presenting in early childhood with progressive motor deterioration, developmental delay, and cerebellar ataxia. The gene shows extremely high constraint against loss-of-function variants, indicating that such mutations are likely pathogenic when found in patients with compatible clinical presentations.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
82
P/LP submissions
0%
P/LP missense
1.25
LOEUF
Mechanism
Clinical SummaryPOLR3D
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
82 unique Pathogenic / Likely Pathogenic· 79 VUS of 175 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.25LOEUF
pLI 0.000
Z-score 0.68
OE 0.84 (0.581.25)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.36Z-score
OE missense 0.93 (0.831.05)
195 obs / 209.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.84 (0.581.25)
00.351.4
Missense OE0.93 (0.831.05)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 18 / 21.4Missense obs/exp: 195 / 209.6Syn Z: -0.80

ClinVar Variant Classifications

175 submitted variants in ClinVar

Classification Summary

Pathogenic78
Likely Pathogenic4
VUS79
Likely Benign1
78
Pathogenic
4
Likely Pathogenic
79
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
78
0
78
Likely Pathogenic
0
0
4
0
4
VUS
0
70
9
0
79
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total071910162

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

View in ClinVar →

Protein Context — Lollipop Plot

POLR3D · 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
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC