POLR3A

Chr 10AR

RNA polymerase III subunit A

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.882 OMIM phenotypes
Clinical SummaryPOLR3A
🧬
Gene-Disease Validity (ClinGen)
POLR3A-related disorder · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.88LOEUF
pLI 0.000
Z-score 2.40
OE 0.69 (0.540.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.31Z-score
OE missense 0.76 (0.710.82)
574 obs / 752.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.69 (0.540.88)
00.351.4
Missense OE0.76 (0.710.82)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 47 / 68.4Missense obs/exp: 574 / 752.0Syn Z: 0.53
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePOLR3A-related Wiedemann Rautenstrauch syndromeLOFAR

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

DN
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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

POLR3A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →