POLR1D

Chr 13ADAR

RNA polymerase I and III subunit D

Also known as: AC19, RPA16, RPA9, RPAC2, RPC16, RPO1-3, TCS2

NCBI Gene: 51082ENSG00000186184UniProt: P0DPB6OMIM: 613715

The protein is a common component of RNA polymerases I and III that catalyzes transcription of ribosomal RNA precursors and short non-coding RNAs including tRNAs, snRNAs, and miRNAs. Mutations cause Treacher Collins syndrome, a craniofacial development disorder affecting structures derived from the first and second pharyngeal arches. The condition shows both autosomal dominant and autosomal recessive inheritance patterns.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 1.011 OMIM phenotype
Clinical Summary— POLR1D
🧬
Gene-Disease Validity (ClinGen)
Treacher Collins syndrome 2 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.21) despite low pLI — interpret in context.
📋
ClinVar Variants
52 unique Pathogenic / Likely Pathogenic· 65 VUS of 166 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — POLR1D
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.01LOEUF
pLI 0.364
Z-score 1.57
OE 0.21 (0.07–1.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.17Z-score
OE missense 0.94 (0.78–1.15)
70 obs / 74.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.21 (0.07–1.01)
0≤0.351.4
Missense OE0.94 (0.78–1.15)
0≤0.61.4
Synonymous OE0.76
0≤1.21.6
LoF obs/exp: 1 / 4.7Missense obs/exp: 70 / 74.1Syn Z: 0.99
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePOLR1D-related Treacher Collins syndromeLOFAD
DN
0.6065th %ile
GOF
0.4085th %ile
LOF
0.3841th %ile

The Badonyi & Marsh model scores dominant-negative highest, but genomic evidence most strongly supports loss-of-function (haploinsufficiency) as the primary mechanism.

LOF1 literature citation · 31% of P/LP variants are LoF

Literature Evidence

LOFDauwerse et al. (2011) describe 17 mutations in POLR1D detected in 20 unrelated individuals with clinical diagnoses of Treacher-Collins syndrome and no mutations in TCOF1, including 10 different nonsense variants. This group also describes a 156 kb de novo deletion encompassing all of POLR1D and thePMID:21131976

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

166 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic12
VUS65
Likely Benign18
Benign22
Conflicting3
40
Pathogenic
12
Likely Pathogenic
65
VUS
18
Likely Benign
22
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
2
31
0
40
Likely Pathogenic
9
1
2
0
12
VUS
5
52
8
0
65
Likely Benign
0
0
11
7
18
Benign
0
1
15
6
22
Conflicting
—3
Total21566713160

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

View in ClinVar →

Protein Context — Lollipop Plot

POLR1D · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
A novel pathogenic variant in POLR1D (c.220dup, p.His74ProfsTer8) causes Treacher Collins syndrome type 2 in a Chinese patient: a case report.
Zhu H et al.·BMC Pediatr
2025Open AccessCase report
A POLR1D-regulating single-nucleotide polymorphism as a predictive marker candidate for platinum-based chemotherapy in gastrointestinal cancers.
Mori T et al.·Ther Adv Med Oncol
2025Open Access
Maternal antioxidant treatment partially rescues developmental defects in a Drosophila Polr1D mutant model.
Walker BM et al.·MicroPubl Biol
2025Open AccessFunctional
Tissue-specific requirement of Polr1D in the prothoracic gland for ecdysone-mediated developmental transitions in Drosophila melanogaster.
Walker BM et al.·Dev Dyn
2026
POLR1D, a shared subunit of RNA polymerase I and III, modulates mTORC1 activity.
Gorjão N et al.·Biochim Biophys Acta Mol Cell Res
2025
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients