POLR3A

Chr 10AR

RNA polymerase III subunit A

Also known as: ADDH, C160, HLD7, RPC1, RPC155, WDRTS, hRPC155

NCBI Gene: 11128 ENSG00000148606 UniProt: O14802 OMIM: 614258

The protein is the catalytic component of RNA polymerase III, which synthesizes small RNAs including tRNAs and rRNAs essential for protein synthesis. Biallelic mutations cause hypomyelinating leukodystrophy 7 (with or without oligodontia and hypogonadotropic hypogonadism) and Wiedemann-Rautenstrauch syndrome through an autosomal recessive inheritance pattern. Mutations can cause disease through dominant-negative effects, where mutant protein interferes with normal RNA polymerase III function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is the catalytic component of RNA polymerase III, which synthesizes small RNAs. The encoded protein also acts as a sensor to detect foreign DNA and trigger an innate immune response. [provided by RefSeq, Aug 2011]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.882 OMIM phenotypes

Clinical Summary— POLR3A

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Gene-Disease Validity (ClinGen)

POLR3A-related disorder · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.88LOEUF

pLI 0.000

Z-score 2.40

OE 0.69 (0.54–0.88)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.31Z-score

OE missense 0.76 (0.71–0.82)

574 obs / 752.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.69 (0.54–0.88)

0≤0.351.4

Missense OE?0.76 (0.71–0.82)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 47 / 68.4Missense obs/exp: 574 / 752.0Syn Z: 0.53

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitivePOLR3A-related Wiedemann Rautenstrauch syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6840th %ile

GOF

0.4875th %ile

LOF

0.3549th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.