Affinage

POLR3A

DNA-directed RNA polymerase III subunit RPC1 · UniProt O14802

Length
1390 aa
Mass
155.6 kDa
Annotated
2026-06-10
65 papers in source corpus 18 papers cited in narrative 19 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

POLR3A (RPC1/RPC155) encodes the largest catalytic subunit of RNA Polymerase III, which together with POLR3B forms the enzyme's active center responsible for transcribing tRNAs, 5S rRNA, BC200 (BCYRN1), and other small non-coding RNAs essential for translation and cellular homeostasis (PMID:22036171, PMID:21855841, PMID:30898877). Its N-terminal region mediates assembly of the polymerase by engaging the C82-34-31 heterotrimer, and disease-clustered residues in the pore domain control nucleotide access to the catalytic site (PMID:39142551, PMID:33148458). Recessive, monoallelic, and splice-altering POLR3A mutations converge on reduced Pol III output, depleting global tRNA pools and specific transcripts such as BC200, which impairs oligodendroglial differentiation and myelin marker expression; this links POLR3A to hypomyelinating leukodystrophy and to a distinct neuropathy caused by catalytic-region monoallelic variants (PMID:30898877, PMID:42260910, PMID:21855841, PMID:22036171). Beyond loss of catalytic output, individual mutations produce protein-level pathologies: a nonsense allele mislocalizes POLR3A to lysosomes and lowers peri-lysosomal mTOR signaling (PMID:35076634), while frameshift mutations associated with Wiedemann-Rautenstrauch syndrome drive nuclear accumulation of mutant protein, nucleolar abnormalities with TERC sequestration, elevated p53/H2AX signaling, and premature senescence (PMID:32976914, PMID:41081995). POLR3A also functions outside canonical transcription as a cytosolic DNA sensor: cytoplasmic DNA triggers its relocalization to perinuclear sites near STING, activating an IRF3-dependent type I interferon and pro-fibrotic response (PMID:35686918). In vivo, polr3a loss in zebrafish reduces tRNA transcription and ribosome biogenesis, causing tp53-associated neural crest craniofacial defects (PMID:42258504).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2011 High

    Established that POLR3A is the largest catalytic subunit of Pol III and that its mutation reduces protein levels to impair CNS myelination, defining the gene as essential for the leukodystrophy phenotype.

    Evidence Immunoblotting of patient fibroblasts and autopsied brain; genetic mapping and Sanger sequencing across families

    PMID:21855841 PMID:22036171

    Open questions at the time
    • Did not establish the molecular mechanism linking reduced Pol III output to myelination
    • Catalytic activity inferred from structure rather than reconstituted
  2. 2011 Medium

    Defined POLR3A and POLR3B as jointly forming the Pol III active center, anchoring the enzyme's transcriptional activity.

    Evidence Genetic analysis of compound heterozygous mutations combined with structural inference

    PMID:21855841 PMID:22036171

    Open questions at the time
    • No direct in vitro catalytic reconstitution in these reports
    • Subunit contributions to individual transcript classes not resolved
  3. 2016 Medium

    Showed that a splicing-deficient POLR3A founder allele reduces full-length transcript and depletes tRNAs and regulatory ncRNAs, extending impact to the Pol II transcriptome.

    Evidence RNA-seq of patient cells with RT-PCR splicing analysis and tRNA quantification

    PMID:27506977

    Open questions at the time
    • Single lab
    • Causal chain from ncRNA imbalance to disease not established
  4. 2017 Medium

    Demonstrated that intronic POLR3A variants reduce functional transcript in a tissue- and stage-specific manner, broadening the mutational spectrum beyond coding changes.

    Evidence RT-PCR splicing analysis and cohort exome/targeted sequencing with segregation

    PMID:28459997

    Open questions at the time
    • Tissue-specificity mechanism unresolved
    • Quantitative threshold for disease not defined
  5. 2017 High

    Tested whether a single founder mutation suffices for disease in vivo; the knock-in mouse failed to recapitulate hypomyelination, revealing species- or allele-specific dependence.

    Evidence Polr3a G672E knock-in mouse with behavioral, histological, and biochemical phenotyping

    PMID:28407788

    Open questions at the time
    • Does not explain why human carriers develop disease
    • Compound allele combinations not modeled
  6. 2019 High

    Provided isogenic causal evidence that a POLR3A point mutation reduces Pol III output, depletes tRNAs and BC200, and lowers MBP upon oligodendroglial differentiation.

    Evidence CRISPR-engineered cell lines with transcriptomics, proteomics, qPCR, and patient cell validation

    PMID:30898877

    Open questions at the time
    • Relative contribution of each depleted ncRNA to myelination unresolved
    • Did not address dominant vs recessive mechanism
  7. 2018 High

    Identified post-transcriptional regulation of the largest subunit: under stress its yeast ortholog is ubiquitylated and proteasomally degraded after chromatin dissociation, separate from the repression event itself.

    Evidence Yeast Western blotting, ubiquitylation detection, proteasome inhibition, and chromatin occupancy assays

    PMID:30342998

    Open questions at the time
    • E3 ligase not identified
    • Conservation of this turnover in human POLR3A untested
  8. 2020 High

    Mapped disease mutations to the pore domain and showed via reconstituted transcription that combinations of mutations compromise both factor-independent and factor-dependent Pol III activity.

    Evidence Engineered yeast Rpc160 mutants, growth assays, and in vitro transcription with affinity-purified Pol III

    PMID:33148458

    Open questions at the time
    • Single mutations were phenotypically silent in yeast
    • Direct translation to human catalytic defect inferred
  9. 2020 Medium

    Established a loss-of-function hierarchy by rescue, showing wild-type but not the p.Val1241Met POLR3A restores Pol III target gene expression.

    Evidence qRT-PCR and overexpression rescue in patient fibroblasts with RT-PCR splicing analysis

    PMID:33134517

    Open questions at the time
    • Single lab
    • Target genes assayed are a limited panel
  10. 2020 Medium

    Revealed a protein-mislocalization mechanism: a nonsense allele aggregates in lysosomes, lowers peri-lysosomal mTOR signaling, and impairs differentiation, with partial mTOR-activator rescue.

    Evidence Confocal lysosome co-localization, mTOR signaling assays, oligodendroglial differentiation, and ibuprofen treatment

    PMID:35076634

    Open questions at the time
    • Mechanism of lysosomal targeting unknown
    • mTOR link based on a single mutant
  11. 2020 Medium

    Connected POLR3A frameshift mutation to a senescence pathology, with nuclear accumulation of mutant protein, nucleolar expansion, and elevated p53/H2AX signaling.

    Evidence RT-qPCR, immunoblotting, confocal localization, SA-β-gal, and pP53/pH2AX immunofluorescence in WRS fibroblasts

    PMID:32976914

    Open questions at the time
    • Causal link from nucleolar change to senescence not dissected
    • Single lab
  12. 2023 Medium

    Uncovered a non-transcriptional role: cytoplasmic DNA drives POLR3A perinuclear relocalization to STING, activating IRF3-dependent interferon and pro-fibrotic responses.

    Evidence Confocal localization, siRNA knockdown, IRF3 ChIP on the MCP-1 promoter, and STING-knockout/bleomycin mouse models

    PMID:35686918

    Open questions at the time
    • Mechanism of DNA recognition by POLR3A unresolved
    • Single lab
  13. 2024 Medium

    Demonstrated that a missense mutant fails to enhance Pol III transcription despite higher expression, indicating a dominant-negative/loss-of-function effect on multiple targets.

    Evidence Overexpression transfection with RT-qPCR of 5S rRNA, tRNA Leu-CAA, BC200, MBP, and 18S rRNA

    PMID:38561452

    Open questions at the time
    • Dominant-negative versus loss-of-function not formally distinguished
    • Single lab
  14. 2024 High

    Defined the N-terminal region of the largest subunit as the assembly module that binds the C82-34-31 heterotrimer, linking its overproduction to altered tRNA gene occupancy.

    Evidence Yeast overdose suppressor screen, ChIP for Pol III occupancy, tRNA synthesis assays, and Co-IP of C160/C34/C82

    PMID:39142551

    Open questions at the time
    • Structural basis of the N-terminal interaction not solved
    • Human POLR3A assembly inferred from yeast
  15. 2024 Medium

    Placed POLR3A within hormonal control of tRNA genes, showing PR co-occupancy and Maf1 co-recruitment are required for progestin-induced tRNA repression.

    Evidence ChIP-seq for POLR3A/PR/Brf1/Maf1 with nascent tRNA assays and Maf1 knockdown (preprint)

    Open questions at the time
    • Preprint, single lab
    • Direct PR-POLR3A contact not demonstrated
  16. 2025 Medium

    Linked POLR3A dysfunction to telomerase RNA metabolism, showing mutant protein causes nucleolar abnormalities and sequesters TERC in nucleoli.

    Evidence WRS iPSC reprogramming with nucleolar immunofluorescence and TERC FISH imaging

    PMID:41081995

    Open questions at the time
    • Functional consequence of TERC sequestration for telomerase activity untested
    • Single lab
  17. 2026 High

    Defined a distinct monoallelic neuropathy mechanism: catalytic-region variants impair Pol III activity and deplete tRNAs without altering POLR3A expression, localization, or subunit interactions.

    Evidence Patient-cell transcriptomics, tRNA quantification, fractionation, interactomics, and structural modelling

    PMID:42260910

    Open questions at the time
    • How catalytic depletion produces peripheral rather than central pathology unresolved
    • Specific affected tRNA isoacceptors not fully mapped
  18. 2026 High

    Established polr3a loss in a vertebrate causes neural-crest craniofacial defects via reduced tRNA transcription and ribosome biogenesis, with tp53 upregulation insufficient to explain the phenotype.

    Evidence Zebrafish loss-of-function mutant with skeletal staining, cell death and ribosome assays, scRNA-seq, and Tp53 inhibition

    PMID:42258504

    Open questions at the time
    • Additional downstream effectors beyond tp53 unidentified
    • Cell-type specificity of vulnerability unresolved
  19. 2026 High

    Demonstrated a therapeutic splicing-correction strategy, identifying mutation-induced splicing aberrations and rescuing them with antisense oligonucleotides.

    Evidence CRISPR-dCas13Rx splicing interference, minigene assays, and ASO rescue with RT-PCR

    PMID:41732205

    Open questions at the time
    • In vivo efficacy not demonstrated
    • Fraction of disease alleles amenable to ASO correction unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct POLR3A mutations produce divergent tissue phenotypes (hypomyelination, neuropathy, progeroid senescence, craniofacial defects) from a shared reduction in Pol III output remains unresolved.
  • No unifying model linking specific tRNA/ncRNA deficits to specific tissue vulnerabilities
  • Genotype-phenotype rules for coding vs splice vs mislocalizing alleles undefined
  • Mechanism of the non-canonical DNA-sensing role versus the transcriptional role not integrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 4 GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 3 GO:0005730 nucleolus 2 GO:0005764 lysosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-1266738 Developmental Biology 1 R-HSA-168256 Immune System 1
Partners
MAF1PGRPOLR3BPOLR3FPOLR3GPOLR3HSTING1
Complex memberships
RNA Polymerase III

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 POLR3A encodes the largest (RPC1/RPC155) catalytic subunit of RNA Polymerase III; recessive missense and insertion mutations in POLR3A cause a significant decrease in POLR3A protein levels in patient fibroblasts and brain tissue, with greater reduction in cerebral white matter than cortex, establishing POLR3A as essential for CNS myelination. Immunoblotting of patient-derived fibroblasts and autopsied brain tissue; Sanger sequencing; genetic mapping American journal of human genetics High 21855841 22036171
2011 POLR3A (RPC1) and POLR3B (RPC2), the two largest Pol III subunits, together form the catalytic/active center of RNA Polymerase III and are jointly responsible for its transcriptional activity, including synthesis of tRNAs and 5S rRNA. Genetic analysis combined with functional inference from known Pol III structural biology; compound heterozygous mutations in POLR3A and POLR3B both disrupt catalytic activity American journal of human genetics Medium 21855841 22036171
2016 A POLR3A founder mutation causing aberrant splicing and partial deficiency of full-length transcript leads to an overall decrease in Pol III-transcribed tRNA levels and imbalance in regulatory ncRNAs (snRNAs and snoRNAs), with downstream complex effects on the Pol II transcriptome affecting general RNA metabolism regulation. Transcriptome-wide analysis (RNA-seq) of patient-derived cells; RT-PCR splicing analysis; tRNA quantification Human molecular genetics Medium 27506977
2017 A deep-intronic POLR3A mutation (c.1909+22G>A) activates a cryptic splice site in a tissue- and developmental stage-specific manner, establishing that non-coding/intronic variants in POLR3A reduce functional transcript levels in a tissue-specific fashion. RT-PCR and RNA splicing analysis; exome and targeted sequencing of cohort; segregation analysis Brain : a journal of neurology Medium 28459997
2017 Knock-in mice homozygous (KI/KI) or compound heterozygous (KI/KO) for the French Canadian founder Polr3a G672E mutation show no overt myelination defects and normal Pol III transcript levels in brain, demonstrating that this single mutation in mice is insufficient to recapitulate the human hypomyelinating phenotype. Knock-in mouse model; behavioral tests; Luxol Fast Blue myelin staining; myelin protein quantification; qRT-PCR of Pol III transcripts Molecular brain High 28407788
2019 CRISPR-Cas9 introduction of the POLR3A c.2554A→G (p.M852V) mutation into human cell lines reduces Pol III transcriptional output, causes a global reduction in tRNA levels, and specifically down-regulates brain cytoplasmic BC200 RNA (BCYRN1); in POLR3A-mutant oligodendroglial cells, MBP mRNA levels are significantly decreased upon differentiation. Genomic BC200 deletion causes larger transcriptomic and proteomic changes than POLR3A mutation alone. CRISPR-Cas9 mutagenesis; transcriptomic profiling; RT-qPCR; proteomics; patient-derived fibroblasts The Journal of biological chemistry High 30898877
2018 Repression of Pol III transcription in S. cerevisiae under stress conditions leads to ubiquitylation of the largest Pol III subunit C160 (the yeast homolog of POLR3A/RPC1) and its subsequent proteasomal degradation, downstream of Pol III dissociation from chromatin. Blocking proteasomal degradation of C160 does not prevent proper transcriptional repression. Western blotting for C160 protein levels; detection of ubiquitylated C160; proteasome inhibitor treatment; chromatin occupancy assays; respiratory/rapamycin growth conditions Biochimica et biophysica acta. Gene regulatory mechanisms High 30342998
2020 HLD7-associated nonsense POLR3A mutation R140X causes the mutant protein to localize primarily as aggregates in lysosomes (rather than the nucleus as for wild-type protein), decreases mTOR signaling around lysosomes, and impairs oligodendroglial cell differentiation and myelin marker protein expression. Ibuprofen, an mTOR activator, partially rescues differentiation defects in cells expressing the R140X mutant. Fluorescence microscopy/confocal imaging; lysosome co-localization assay; mTOR signaling assays; oligodendroglial differentiation assay; myelin marker protein expression; ibuprofen treatment Neurology international Medium 35076634
2020 HLD-causing missense mutations in POLR3A that cluster in the pore domain (which provides nucleotide access to the Pol III active site) were engineered into the yeast Rpc160 homolog; single mutations had no growth or transcription phenotype, but combining the pore mutations with a G672E mutation created double mutants with phenotypes ranging from wild-type to lethal. In the slowest-growing temperature-sensitive double mutant, global tRNA synthesis and RPR1/SNR52 RNA synthesis were compromised, and affinity-purified mutant Pol III showed defects in both factor-independent and factor-dependent transcription in vitro. Yeast genetics (engineered Rpc160 mutations); growth assays; in vitro transcription with affinity-purified Pol III; tRNA synthesis assays; RPR1/SNR52 RNA synthesis assays Gene High 33148458
2020 A POLR3A c.1771-6C>G splicing mutation causes aberrant splicing; in patient fibroblasts, expression levels of Pol III target genes (HNRNPH2, ubiquitin B, lactotransferrin, HSP90AA1) are decreased and are rescued to normal levels by overexpression of wild-type POLR3A but not by the p.Val1241Met variant, demonstrating that Val1241Met is a loss-of-function mutation affecting Pol III transcriptional activity. qRT-PCR; POLR3A overexpression rescue experiment in patient fibroblasts; RT-PCR for aberrant splicing Neurology. Genetics Medium 33134517
2020 In WRS patient fibroblasts, a frameshift POLR3A mutation (c.3772_3773delCT) causes decreased wild-type POLR3A mRNA and protein, increased expression of the mutant protein, and increased nuclear localization of the mutant protein. These changes are associated with increased number/area of nucleoli, elevated pP53 and pH2AX signaling, and premature cellular senescence. RT-qPCR; immunoblotting; confocal microscopy for localization; SA-β-galactosidase senescence assay; immunofluorescence for pP53 and pH2AX Mechanisms of ageing and development Medium 32976914
2023 Macrophage-derived DNA stimulates translocation of POLR3A from the nucleus to the perinuclear region near STING in fibroblasts and HUVECs, activating the POLR3A/STING/type I interferon response, monocyte adhesion, MCP-1 expression, and collagen overproduction. IRF3 (activated downstream of this pathway) directly binds the MCP-1 promoter. Knockdown of POLR3A or STING abolishes this response. Immunofluorescence/confocal microscopy for POLR3A subcellular localization; siRNA knockdown of POLR3A and STING; ChIP for IRF3 binding to MCP-1 promoter; Western blotting; STING knockout mouse model; bleomycin SSc mouse model Rheumatology (Oxford, England) Medium 35686918
2024 Overexpression of wild-type POLR3A significantly enhances Pol III transcription of 5S rRNA and tRNA Leu-CAA; a p.Cys767Phe mutant POLR3A, despite being expressed at higher levels than wild-type, fails to enhance Pol III transcription and instead reduces expression of POLR3A targets (BC200, tRNA Leu-CAA) and MBP/18S rRNA, demonstrating that the mutation causes a dominant-negative or loss-of-function effect on Pol III transcriptional activity. Cell transfection overexpression assay; RT-qPCR of Pol III target transcripts (5S rRNA, tRNA Leu-CAA, BC200, MBP, 18S rRNA) Scientific reports Medium 38561452
2024 Overproduction of the N-terminal fragment of the largest Pol III subunit C160 (C160-NTF, yeast POLR3A homolog) suppresses the maf1Δ phenotype by decreasing tRNA transcription and Pol III occupancy on tRNA genes. C160-NTF alters interactions of C160 with C34 and C82 subunits of the C82-34-31 heterotrimer, suggesting that the N-terminal region of POLR3A mediates assembly of this Pol III subcomplex. Yeast genetics (overdose suppressor screen); ChIP for Pol III occupancy; tRNA synthesis assays (newly synthesized tRNA); co-immunoprecipitation of Pol III subunits (C160/C34/C82 interactions); HA-tag localization by microscopy Gene High 39142551
2025 In WRS iPSCs carrying POLR3A mutations, POLR3A is upregulated during reprogramming; enhanced expression of mutant POLR3A leads to nucleolus abnormalities and sequestration of telomerase RNA component (TERC) in the nucleoli, establishing a functional link between POLR3A dysfunction, nucleolar structure, and telomerase RNA metabolism. iPSC reprogramming; immunofluorescence for nucleolar morphology; FISH/imaging for TERC localization in nucleoli Biogerontology Medium 41081995
2026 In zebrafish, loss of polr3a causes hypoplasia of neural crest cell-derived craniofacial cartilage and bone, reduced tRNA transcription, and reduced ribosome biogenesis. At larval stages, increased cell death occurs in craniofacial cartilage. Single-cell RNA-seq reveals upregulation of tp53, but Tp53 inhibition alone does not rescue craniofacial defects, indicating that additional downstream factors are required. Zebrafish polr3a mutant (loss-of-function); skeletal staining; cell death assays; tRNA transcription assays; ribosome biogenesis assays; single-cell RNA-seq; Tp53 inhibitor treatment PLoS genetics High 42258504
2026 Monoallelic (heterozygous) missense POLR3A variants cause impaired Pol III activity in patient-derived cells, including mis-regulation of individual Pol III targets and global downregulation of tRNA pools, without changes in POLR3A expression, subcellular localization, or subunit interactions. The neuropathy-associated variants cluster in regions critical for Pol III catalytic activity and do not overlap with known biallelic disease-causing variants. Patient-derived cell transcriptomics; tRNA pool quantification; immunoblotting; subcellular fractionation; interactomics (subunit interaction assays); structural modelling Annals of neurology High 42260910
2026 CRISPR-dCas13Rx targeting of POLR3A exon regions harboring disease-causing missense mutations reveals that ~20% of interrogated exon regions affect RNA splicing; minigene assays confirm that specific mutations (in exons 14 and 26) cause splicing aberrations. Antisense oligonucleotides (ASOs) targeting intronic elements identified by this approach rescue correct splicing of POLR3A in EcR293 and oligodendroglioma cell lines. CRISPR-dCas13Rx splicing interference; minigene splicing assays; antisense oligonucleotide (ASO) treatment; RT-PCR splicing analysis Molecular therapy. Nucleic acids High 41732205
2024 Progesterone receptor (PR) co-occupies ~50% of POLR3A-occupied tRNA genes upon progestin treatment, co-recruiting Maf1 to these sites. Maf1 knockdown significantly reduces progestin-induced tRNA transcription repression, establishing that PR-mediated repression of select tRNA genes by POLR3A requires Maf1 as a necessary effector. ChIP-seq for POLR3A, PR, Brf1 (TFIIIB), and Maf1; nascent tRNA transcription assays; Maf1 siRNA knockdown bioRxivpreprint Medium

Source papers

Stage 0 corpus · 65 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy. American journal of human genetics 221 21855841
2014 Clinical spectrum of 4H leukodystrophy caused by POLR3A and POLR3B mutations. Neurology 173 25339210
2011 Mutations in POLR3A and POLR3B encoding RNA Polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy. American journal of human genetics 137 22036171
2017 Hypomorphic mutations in POLR3A are a frequent cause of sporadic and recessive spastic ataxia. Brain : a journal of neurology 99 28459997
2013 Mutations in POLR3A and POLR3B are a major cause of hypomyelinating leukodystrophies with or without dental abnormalities and/or hypogonadotropic hypogonadism. Journal of medical genetics 92 23355746
2016 Transcriptome-wide effects of a POLR3A gene mutation in patients with an unusual phenotype of striatal involvement. Human molecular genetics 58 27506977
2012 4H syndrome with late-onset growth hormone deficiency caused by POLR3A mutations. Archives of neurology 49 22451160
2019 Leukodystrophy-associated POLR3A mutations down-regulate the RNA polymerase III transcript and important regulatory RNA BC200. The Journal of biological chemistry 47 30898877
2018 Bi-allelic POLR3A Loss-of-Function Variants Cause Autosomal-Recessive Wiedemann-Rautenstrauch Syndrome. American journal of human genetics 47 30414627
2018 Specific combinations of biallelic POLR3A variants cause Wiedemann-Rautenstrauch syndrome. Journal of medical genetics 46 30323018
2016 Neonatal progeriod syndrome associated with biallelic truncating variants in POLR3A. American journal of medical genetics. Part A 35 27612211
2017 Absence of neurological abnormalities in mice homozygous for the Polr3a G672E hypomyelinating leukodystrophy mutation. Molecular brain 33 28407788
2020 POLR3A variants in striatal involvement without diffuse hypomyelination. Brain & development 26 31932101
2019 Novel mutations of the POLR3A gene caused POLR3-related leukodystrophy in a Chinese family: a case report. BMC pediatrics 25 31438894
2013 Different patterns of cerebellar abnormality and hypomyelination between POLR3A and POLR3B mutations. Brain & development 23 23643445
2020 GnRH Deficient Patients With Congenital Hypogonadotropic Hypogonadism: Novel Genetic Findings in ANOS1, RNF216, WDR11, FGFR1, CHD7, and POLR3A Genes in a Case Series and Review of the Literature. Frontiers in endocrinology 22 32982993
2019 POLR3A-related spastic ataxia: new mutations and a look into the phenotype. Journal of neurology 22 31637490
2018 Analyses of LMNA-negative juvenile progeroid cases confirms biallelic POLR3A mutations in Wiedemann-Rautenstrauch-like syndrome and expands the phenotypic spectrum of PYCR1 mutations. Human genetics 21 30450527
2013 Novel compound heterozygous mutations of POLR3A revealed by whole-exome sequencing in a patient with hypomyelination. Brain & development 21 23694757
2021 POLR3A variants in hereditary spastic paraparesis and ataxia: clinical, genetic, and neuroradiological findings in a cohort of Italian patients. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 19 34296356
2015 Exome sequencing reveals a novel WDR45 frameshift mutation and inherited POLR3A heterozygous variants in a female with a complex phenotype and mixed brain MRI findings. European journal of medical genetics 19 26096995
2018 A novel homozygous mutation in POLR3A gene causing 4H syndrome: a case report. BMC pediatrics 17 29618326
2020 Nucleolar disruption, activation of P53 and premature senescence in POLR3A-mutated Wiedemann-Rautenstrauch syndrome fibroblasts. Mechanisms of ageing and development 16 32976914
2022 Identification of a Novel Missense Mutation of POLR3A Gene in a Cohort of Sicilian Patients with Leukodystrophy. Biomedicines 15 36140376
2015 POLR3A and POLR3B Mutations in Unclassified Hypomyelination. Neuropediatrics 15 26011300
2020 Unique combination and in silico modeling of biallelic POLR3A variants as a cause of Wiedemann-Rautenstrauch syndrome. European journal of human genetics : EJHG 12 32555393
2023 DNA from macrophages induces fibrosis and vasculopathy through POLR3A/STING/type I interferon axis in systemic sclerosis. Rheumatology (Oxford, England) 11 35686918
2021 Hypomyelinating Leukodystrophy 7 (HLD7)-Associated Mutation of POLR3A Is Related to Defective Oligodendroglial Cell Differentiation, Which Is Ameliorated by Ibuprofen. Neurology international 11 35076634
2020 A novel POLR3A genotype leads to leukodystrophy type-7 in two siblings with unusually late age of onset. BMC neurology 11 32600288
2019 A 42-year-old woman with 4H leukodystrophy caused by a homozygous mutation in POLR3A gene. Chinese medical journal 10 31306222
2018 Repression of yeast RNA polymerase III by stress leads to ubiquitylation and proteasomal degradation of its largest subunit, C160. Biochimica et biophysica acta. Gene regulatory mechanisms 10 30342998
2023 Craniofacial features of POLR3-related leukodystrophy caused by biallelic variants in POLR3A, POLR3B and POLR1C. Journal of medical genetics 9 37197783
2020 Interpretation challenges of novel dual-class missense and splice-impacting variant in POLR3A-related late-onset hereditary spastic ataxia. Molecular genetics & genomic medicine 9 32597037
2020 Neurodevelopmental regression, severe generalized dystonia, and metabolic acidosis caused by POLR3A mutations. Neurology. Genetics 8 33134517
2020 Functional characterization of Polr3a hypomyelinating leukodystrophy mutations in the S. cerevisiae homolog, RPC160. Gene 8 33148458
2024 Clinical phenotype and genetic function analysis of a family with hypomyelinating leukodystrophy-7 caused by POLR3A mutation. Scientific reports 6 38561452
2022 Developmental regression and movement disorder as a phenotypic variant of POLR3A Mutation-Case report. Clinical case reports 6 36397839
2023 A novel variant of the POLR3A gene in a Chinese patient with POLR3-related leukodystrophy. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 5 36988728
2022 Circ-POLR3A accelerates TGF-β2-induced promotion in cell viability, migration, and invasion of lens epithelial cells via miR-31/TXNIP signaling cascade. Journal of biochemical and molecular toxicology 5 35730126
2021 Spinal cord-predominant neuropathology in an adult-onset case of POLR3A-related spastic ataxia. Neuropathology : official journal of the Japanese Society of Neuropathology 5 34753215
2020 Multimodal evaluation of an Italian family with a hereditary spastic paraplegia and POLR3A mutations. Annals of clinical and translational neurology 5 33085208
2024 POLR3-related leukodystrophy caused by biallelic POLR3A and 1C pathogenic variants: a single-center experience. Frontiers in neurology 4 38550343
2023 A Chinese patient with POLR3A-related leukodystrophy: a case report and literature review. Frontiers in neurology 4 37965164
2016 [A Case of Pol III-related Leukodystrophy with Homozygous Mutation in POLR3A]. Brain and nerve = Shinkei kenkyu no shinpo 4 27852030
2024 Further delineation of Wiedemann-Rautenstrauch syndrome linked with POLR3A. Molecular genetics & genomic medicine 3 38348603
2022 A novel variant of the POLR3A gene in a patient with hypomyelinating POLR3-related leukodystrophy. Clinica chimica acta; international journal of clinical chemistry 3 35691411
2021 Two intronic cis-acting variants in both alleles of the POLR3A gene cause progressive spastic ataxia with hypodontia. Clinical genetics 3 33491183
2013 [A case of hypomyelinating leukodystrophy with new homozygous mutation in POLR3A]. Rinsho shinkeigaku = Clinical neurology 3 23965854
2004 Molecular mapping of the crown rust resistance gene rpc1 in barley. Phytopathology 3 18943106
2024 Production of an induced pluripotent stem cell line CSSi018-A (14192) from a patient with hypomyelinating leukodystrophy 7 (HLD7) carrying biallelic variants of POLR3A (c.1802 T > A; c.4072G > A). Stem cell research 2 38852424
2026 RNA-based discovery and correction of splicing defects caused by POLR3A missense mutations. Molecular therapy. Nucleic acids 1 41732205
2025 POLR3A rare variants in a patient with intellectual disability, ataxic gait and cortical malformations: a case-report. Italian journal of pediatrics 1 40518520
2024 An iPSC model for POLR3A-associated spastic ataxia: Generation of three unrelated patient cell lines. Stem cell research 1 38437768
2024 Tremor Ataxia With Central Hypomyelation Phenotype Related to a Recurrent POLR3A Mutation in Six Unrelated Tunisian Families. Molecular genetics & genomic medicine 1 39436788
2026 RNA Polymerase III subunit Polr3a is required for craniofacial cartilage and bone development. bioRxiv : the preprint server for biology 0 41542503
2026 Novel POLR3A Gene Mutation Results in Wiedemann-Rautenstrauch Syndrome With Striking Cutis Laxa and Myelofibrosis. The Journal of dermatology 0 41549341
2026 Study of POLR3A variants in a family trio suggests mutation-specific pathogenetic mechanisms: insights from integrative OMIC approaches. Cell communication and signaling : CCS 0 41634725
2026 POLR3A-related syndrome complicated with cerebral abscesses: a case report and literature review. Frontiers in genetics 0 41716259
2026 Expanding the genetic spectrum of neurogenetic disorders in moroccan families by exome sequencing: identification of candidate variants in RYR3, POLR3A, and LAMA2. Molecular biology reports 0 42113100
2026 RNA Polymerase III subunit Polr3a is required for craniofacial cartilage and bone development in zebrafish. PLoS genetics 0 42258504
2026 Monoallelic POLR3A Variants Cause Early-Onset Peripheral Neuropathy. Annals of neurology 0 42260910
2025 Clinical and molecular insights into Wiedemann-Rautenstrauch syndrome: A case report and genetic analysis of the c.2707G>A variant in the POLR3A gene. Experimental gerontology 0 40912518
2025 "Deep Brain Stimulation of the Ventral Intermediate Nucleus of the Thalamus for Tremor in Polr3a-Related Tremor-ataxia Syndrome: A Two-case Report". Tremor and other hyperkinetic movements (New York, N.Y.) 0 40917817
2025 POLR3A mutations cause nucleolus abnormalities and aberrant telomerase RNA metabolism in induced pluripotent stem cells from Wiedemann-Rautenstrauch premature aging syndrome patient. Biogerontology 0 41081995
2024 Functional suppression of a yeast maf1 deletion mutant by overdose of the N-terminal fragment of the largest RNA polymerase III subunit, C160. Gene 0 39142551

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