POLR1C

Chr 6

RNA polymerase I and III subunit C

Also known as: AC40, HLD11, RPA39, RPA40, RPA5, RPAC1, RPC40, TCS3

NCBI Gene: 9533ENSG00000171453UniProt: O15160

The protein encoded by this gene is a subunit of both RNA polymerase I and RNA polymerase III complexes. The encoded protein is part of the Pol core element. Mutations in this gene have been associated with Treacher Collins syndrome (TCS) and hypomyelinating leukodystrophy 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Primary Disease Associations & Inheritance

UniProtTreacher Collins syndrome 3
UniProtLeukodystrophy, hypomyelinating, 11
426
ClinVar variants
47
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— POLR1C
🧬
Gene-Disease Validity (ClinGen)
Treacher Collins syndrome 3 · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
47 Pathogenic / Likely Pathogenic· 215 VUS of 426 total submissions
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?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.40LOEUF
pLI 0.000
Z-score 0.34
OE 0.91 (0.61–1.40)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.44Z-score
OE missense 1.29 (1.16–1.43)
252 obs / 195.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.91 (0.61–1.40)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.29 (1.16–1.43)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.24
0≤1.21.6
LoF obs/exp: 15 / 16.5Missense obs/exp: 252 / 195.2Syn Z: -1.58

ClinVar Variant Classifications

426 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic24
VUS215
Likely Benign138
Benign11
Conflicting15
23
Pathogenic
24
Likely Pathogenic
215
VUS
138
Likely Benign
11
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
3
14
0
23
Likely Pathogenic
12
8
4
0
24
VUS
0
197
15
3
215
Likely Benign
0
3
62
73
138
Benign
1
4
5
1
11
Conflicting
—15
Total1921510077426

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

View in ClinVar →

Protein Context — Lollipop Plot

POLR1C · protein map & ClinVar variants

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

Gene2Phenotype Curations

POLR1C-related leukodystrophy

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — POLR1C
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Treacher Collins Syndrome: Genetics, Clinical Features and Management.
Marszałek-Kruk BA et al.·Genes (Basel)
2021Review
Comprehensive genotype-phenotype analysis in POLR3-related disorders.
Michell-Robinson MA et al.·HGG Adv
2025
Autosomal recessive Treacher Collins syndrome due to POLR1C mutations: Report of a new family and review of the literature.
Ghesh L et al.·Am J Med Genet A
2019Review
Craniofacial features of POLR3-related leukodystrophy caused by biallelic variants in POLR3A, POLR3B and POLR1C.
Mirchi A et al.·J Med Genet
2023
Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C.
Pelletier F et al.·J Clin Endocrinol Metab
2021
Pathogenesis of POLR1C-dependent Type 3 Treacher Collins Syndrome revealed by a zebrafish model.
Lau MC et al.·Biochim Biophys Acta
2016Functional
Treacher Collins syndrome: New insights from animal models.
Tse WK·Int J Biochem Cell Biol
2016Review
Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III.
Thiffault I et al.·Nat Commun
2015
4H Leukodystrophy: Lessons from 3T Imaging.
Cayami FK et al.·Neuropediatrics
2018
[Pathogenic genes and clinical therapeutic strategies for Treacher Collins syndrome].
Yin B et al.·Hua Xi Kou Qiang Yi Xue Za Zhi
2019Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools