POLR3A
DNA-directed RNA polymerase III subunit RPC1
Also known as: C160, hRPC155, RPC1, RPC1_HUMAN, RPC155
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- O14802
- Gene
- POLR3A
- Ensembl
- ENSG00000148606
- Chromosome
- 10
- Canonical length
- 1390 aa
- Protein class
- Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins, RNA polymerase related proteins
- Subcellular location
- Nucleoplasm
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
1390 residues, UniProt reviewed canonical sequence.
>O14802|POLR3A
1 MVKEQFRETD VAKKISHICF GMKSPEEMRQ QAHIQVVSKN LYSQDNQHAP LLYGVLDHRM
61 GTSEKDRPCE TCGKNLADCL GHYGYIDLEL PCFHVGYFRA VIGILQMICK TCCHIMLSQE
121 EKKQFLDYLK RPGLTYLQKR GLKKKISDKC RKKNICHHCG AFNGTVKKCG LLKIIHEKYK
181 TNKKVVDPIV SNFLQSFETA IEHNKEVEPL LGRAQENLNP LVVLNLFKRI PAEDVPLLLM
241 NPEAGKPSDL ILTRLLVPPL CIRPSVVSDL KSGTNEDDLT MKLTEIIFLN DVIKKHRISG
301 AKTQMIMEDW DFLQLQCALY INSELSGIPL NMAPKKWTRG FVQRLKGKQG RFRGNLSGKR
361 VDFSGRTVIS PDPNLRIDEV AVPVHVAKIL TFPEKVNKAN INFLRKLVQN GPEVHPGANF
421 IQQRHTQMKR FLKYGNREKM AQELKYGDIV ERHLIDGDVV LFNRQPSLHK LSIMAHLARV
481 KPHRTFRFNE CVCTPYNADF DGDEMNLHLP QTEEAKAEAL VLMGTKANLV TPRNGEPLIA
541 AIQDFLTGAY LLTLKDTFFD RAKACQIIAS ILVGKDEKIK VRLPPPTILK PVTLWTGKQI
601 FSVILRPSDD NPVRANLRTK GKQYCGKGED LCANDSYVTI QNSELMSGSM DKGTLGSGSK
661 NNIFYILLRD WGQNEAADAM SRLARLAPVY LSNRGFSIGI GDVTPGQGLL KAKYELLNAG
721 YKKCDEYIEA LNTGKLQQQP GCTAEETLEA LILKELSVIR DHAGSACLRE LDKSNSPLTM
781 ALCGSKGSFI NISQMIACVG QQAISGSRVP DGFENRSLPH FEKHSKLPAA KGFVANSFYS
841 GLTPTEFFFH TMAGREGLVD TAVKTAETGY MQRRLVKSLE DLCSQYDLTV RSSTGDIIQF
901 IYGGDGLDPA AMEGKDEPLE FKRVLDNIKA VFPCPSEPAL SKNELILTTE SIMKKSEFLC
961 CQDSFLQEIK KFIKGVSEKI KKTRDKYGIN DNGTTEPRVL YQLDRITPTQ VEKFLETCRD
1021 KYMRAQMEPG SAVGALCAQS IGEPGTQMTL KTFHFAGVAS MNITLGVPRI KEIINASKAI
1081 STPIITAQLD KDDDADYARL VKGRIEKTLL GEISEYIEEV FLPDDCFILV KLSLERIRLL
1141 RLEVNAETVR YSICTSKLRV KPGDVAVHGE AVVCVTPREN SKSSMYYVLQ FLKEDLPKVV
1201 VQGIPEVSRA VIHIDEQSGK EKYKLLVEGD NLRAVMATHG VKGTRTTSNN TYEVEKTLGI
1261 EAARTTIINE IQYTMVNHGM SIDRRHVMLL SDLMTYKGEV LGITRFGLAK MKESVLMLAS
1321 FEKTADHLFD AAYFGQKDSV CGVSECIIMG IPMNIGTGLF KLLHKADRDP NPPKRPLIFD
1381 TNEFHIPLVTLocalizationUniProt · AlphaFold · HPA
Whether an antibody against POLR3A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.28
- Highest tissue expression
- 11 nTPM
Expression across tissuesHPA
Tissue
- cerebellum: 11 nTPM
- skeletal muscle: 11 nTPM
- pituitary gland: 9.7 nTPM
- cerebral cortex: 8.7 nTPM
- tongue: 6.3 nTPM
- retina: 5.9 nTPM
Single-cell type
- corticotrophs: 130 nCPM
- somatotrophs: 124 nCPM
- cone photoreceptor cells: 66 nCPM
- myonuclei: 58 nCPM
- retinal horizontal cells: 58 nCPM
- adrenal cortex cells: 53 nCPM
Immune cell
- memory CD8 T-cell: 2.1 nTPM
- intermediate monocyte: 1.9 nTPM
- naive CD8 T-cell: 1.9 nTPM
- gdT-cell: 1.8 nTPM
- T-reg: 1.7 nTPM
- MAIT T-cell: 1.6 nTPM
Brain region
- cerebral cortex: 7.2 nTPM
- pons: 5.5 nTPM
- basal ganglia: 5.2 nTPM
- thalamus: 3.9 nTPM
- medulla oblongata: 3.8 nTPM
- white matter: 3.5 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about POLR3A.
Disease | AllUniProt
Conditions POLR3A is implicated in, by any mechanism.
- Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism (HLD7) MIM:607694
- Wiedemann-Rautenstrauch syndrome (WDRTS) MIM:264090
Disease | GeneticClinVar
132 pathogenic / likely-pathogenic of 1,353 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism
- Neonatal pseudo-hydrocephalic progeroid syndrome
- Leukodystrophy
- POLR3A-related disorder
- POLR-related leukodystrophy
Disease | ImmuneIEDB
Conditions an epitope on POLR3A was assayed in.
- systemic scleroderma B cell
Disease | AutoantibodyPubMed
Conditions in which antibodies against POLR3A are reported. Each links to that disease's full target list.
- Scleroderma, Systemic 96
- Acute Kidney Injury 8
- Lung Diseases, Interstitial 7
- Raynaud Disease 6
- Lung Neoplasms 5
- Myositis 4
- Scleroderma, Localized 4
- Arthritis, Rheumatoid 3
- Breast Neoplasms 3
- Kidney Diseases 3
- Renal Insufficiency 3
- Sjogren's Syndrome 3
Showing 12 of 15 — disease pages carrying at least 10 antigens.
ReferencesPubMed · IEDB
Publications for POLR3A from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
122 publications
- Association of the autoimmune disease scleroderma with an immunologic response to cancer.
2014 · Science · RCR 9.3 · 333 citations - Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma.
2014 · Arthritis Res Ther · RCR 6 · 156 citations - Autoantibody reactive with RNA polymerase III in systemic sclerosis.
1993 · Ann Intern Med · RCR 5.8 · 185 citations - Autoantibodies as predictive tools in systemic sclerosis.
2010 · Nat Rev Rheumatol · RCR 4.4 · 148 citations - Malignancies in Patients with Anti-RNA Polymerase III Antibodies and Systemic Sclerosis: Analysis of the EULAR Scleroderma Trials and Research Cohort and Possible Recommendations for Screening.
2017 · J Rheumatol · RCR 4.3 · 91 citations
Show 20 more of 122 total
- Characterization of Incident Interstitial Lung Disease in Late Systemic Sclerosis.
2025 · Arthritis Rheumatol · RCR 4.2 · 12 citations - Prevalence, correlates and clinical usefulness of antibodies to RNA polymerase III in systemic sclerosis: a cross-sectional analysis of data from an Australian cohort.
2011 · Arthritis Res Ther · RCR 4.2 · 126 citations - Autoantibodies and scleroderma phenotype define subgroups at high-risk and low-risk for cancer.
2018 · Ann Rheum Dis · RCR 4 · 89 citations - Examination of autoantibody status and clinical features associated with cancer risk and cancer-associated scleroderma.
2015 · Arthritis Rheumatol · RCR 3.7 · 93 citations - Incidence and predictors of cutaneous manifestations during the early course of systemic sclerosis: a 10-year longitudinal study from the EUSTAR database.
2016 · Ann Rheum Dis · RCR 3.3 · 68 citations - Plasma cytokine profiles in systemic sclerosis: associations with autoantibody subsets and clinical manifestations.
2009 · Arthritis Res Ther · RCR 3.2 · 118 citations - Disease subsets, antinuclear antibody profile, and clinical features in 127 French and 247 US adult patients with systemic sclerosis.
2007 · J Rheumatol · RCR 3.1 · 104 citations - Renal disease in scleroderma: an update on evaluation, risk stratification, pathogenesis and management.
2012 · Curr Opin Rheumatol · RCR 3 · 78 citations - Validation of potential classification criteria for systemic sclerosis.
2012 · Arthritis Care Res (Hoboken) · RCR 2.9 · 73 citations - Phenotypic Heterogeneity of Fulminant COVID-19--Related Myocarditis in Adults.
2022 · J Am Coll Cardiol · RCR 2.8 · 39 citations - Calcinosis is associated with digital ischaemia in systemic sclerosis-a longitudinal study.
2016 · Rheumatology (Oxford) · RCR 2.8 · 51 citations - Diversity and Epitope Spreading of Anti-RNA Polymerase III Antibodies in Systemic Sclerosis: A Potential Biomarker for Skin and Lung Involvement.
2025 · Arthritis Rheumatol · RCR 2.7 · 7 citations - Clinical and immunologic predictors of scleroderma renal crisis in Japanese systemic sclerosis patients with anti-RNA polymerase III autoantibodies.
2015 · Arthritis Rheumatol · RCR 2.5 · 57 citations - Risk Factors for Future Scleroderma Renal Crisis at Systemic Sclerosis Diagnosis.
2019 · J Rheumatol · RCR 2.5 · 39 citations - Correlation of interferon-inducible chemokine plasma levels with disease severity in systemic sclerosis.
2013 · Arthritis Rheum · RCR 2.5 · 85 citations - Cancer and scleroderma: a paraneoplastic disease with implications for malignancy screening.
2015 · Curr Opin Rheumatol · RCR 2.4 · 62 citations - Malignancies in Italian patients with systemic sclerosis positive for anti-RNA polymerase III antibodies.
2011 · J Rheumatol · RCR 2.3 · 77 citations - Enzyme-linked immunosorbent assay for detection of anti-RNA polymerase III antibody: analytical accuracy and clinical associations in systemic sclerosis.
2005 · Arthritis Rheum · RCR 2.2 · 78 citations - Scleroderma: the role of serum autoantibodies in defining specific clinical phenotypes and organ system involvement.
2014 · Curr Opin Rheumatol · RCR 2.1 · 53 citations - Circulating Anti-Nuclear Antibodies in Systemic Sclerosis: Utility in Diagnosis and Disease Subsetting.
2017 · J Nippon Med Sch · RCR 2.1 · 41 citations
Reference: B cellIEDB
1 publication
- Computational analysis of high-density peptide microarray data with application from systemic sclerosis to multiple sclerosis.
2012 · Autoimmun Rev · RCR 1 · 35 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.88
- gnomAD pLI
- 0
- gnomAD missense Z
- 2.31
- DepMap mean gene effect
- -2.31
- DepMap dependency class
- pan
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- defense response to virus
- DNA-templated transcription
- innate immune response
- positive regulation of interferon-beta production
- tRNA transcription by RNA polymerase III
Molecular functions
- chromatin binding
- DNA binding
- DNA-directed RNA polymerase activity
- DNA/RNA hybrid binding
- magnesium ion binding
- zinc ion binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- RNA polymerase, alpha subunit
- RNA polymerase, N-terminal
- RNA polymerase Rpb1, domain 3
- RNA polymerase Rpb1, domain 1
- RNA polymerase Rpb1, domain 5
- RNA polymerase Rpb1, domain 4
- RNA polymerase Rpb1, funnel domain superfamily
- RNA polymerase Rpb1, domain 3 superfamily
- RNA polymerase Rpb1, clamp domain superfamily
- RNA polymerase Rpb1, domain 2
- RNA polymerase Rpb1, domain 3
- RNA polymerase Rpb1, domain 1
- RNA polymerase Rpb1, domain 5
- RNA polymerase Rpb1, domain 4
- DNA-directed RNA polymerase III subunit RPC1
- DNA-directed RNA polymerase III subunit RPC1, N-terminal
- DNA-directed RNA polymerase III subunit RPC1, C-terminal
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of POLR3A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads POLR3A as an antibody target. Whether an autoantibody or antibody against POLR3A could matter depends on whether native POLR3A is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
POLR3A is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label POLR3A as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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