POLR1D

Chr 13

RNA polymerase I and III subunit D

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

NCBI Gene: 51082 ENSG00000186184 UniProt: P0DPB6

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a component of the RNA polymerase I and RNA polymerase III complexes, which function in the synthesis of ribosomal RNA precursors and small RNAs, respectively. Mutations in this gene are a cause of Treacher Collins syndrome (TCS), a craniofacial development disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2011]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtTreacher Collins syndrome 2

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Treacher Collins syndrome 2 · AD · ClinGen 2022

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.01

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — POLR1D

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.21 (0.07–1.01)

0≤0.351.4

Missense OE?0.94 (0.78–1.15)

0≤0.61.4

Synonymous OE?0.76

0≤1.21.6

LoF obs/exp: 1 / 4.7Missense obs/exp: 70 / 74.1Syn Z: 0.99

Background carrier burden — how many people carry a rare variant somewhere in POLR1D?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 320

330 rare PASS variants

Rare truncating (LoF)

1 in 3,200

57 rare PASS variants

Rare synonymous (reference)

1 in 420

117 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for POLR1D. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 440	1 in 2,800
South Asian	~43k	1 in 300	1 in 6,100
Remaining (unassigned)	~30k	1 in 230	1 in 3,200
European (Finnish)	~27k	1 in 1,900	≈ 1 in 27,000
Admixed American	~22k	1 in 180	≈ 1 in 7,200
African / African American	~21k	1 in 210	1 in 3,200
East Asian	~20k	1 in 240	none seen
Ashkenazi Jewish	~13k	1 in 2,600	none seen
Middle Eastern	~2,884	1 in 320	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓