POLR3A

Summary

POLR3A (RNA polymerase III subunit A, HGNC:30074) is a protein-coding gene on chromosome 10q22.3, encoding DNA-directed RNA polymerase III subunit RPC1 (O14802). Catalytic core component of RNA polymerase III (Pol III), a DNA-dependent RNA polymerase which synthesizes small non-coding RNAs using the four ribonucleoside triphosphates as substrates. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

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.

Source: NCBI Gene 11128 — RefSeq curated summary.

At a glance

• Gene–disease (curated): POLR3A-related disorder (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 1,241 total — 51 pathogenic, 50 likely-pathogenic
• Phenotypes (HPO): 224
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_007055

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30074
Approved symbol	POLR3A
Name	RNA polymerase III subunit A
Location	10q22.3
Locus type	gene with protein product
Status	Approved
Aliases	RPC1, RPC155, hRPC155, C160
Ensembl gene	ENSG00000148606
Ensembl biotype	protein_coding
OMIM	614258
Entrez	11128

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 12 retained_intron, 6 protein_coding, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000372371, ENST00000472014, ENST00000473588, ENST00000484760, ENST00000698724, ENST00000698725, ENST00000698726, ENST00000698727, ENST00000698728, ENST00000698729, ENST00000698730, ENST00000698731, ENST00000698732, ENST00000698733, ENST00000698734, ENST00000698735, ENST00000698736, ENST00000698737, ENST00000698738, ENST00000698739, ENST00000865317, ENST00000865318, ENST00000912219, ENST00000912220

RefSeq mRNA: 1 — MANE Select: NM_007055 NM_007055

CCDS: CCDS7354

Canonical transcript exons

ENST00000372371 — 31 exons

Exon	Start	End
ENSE00000933817	78019162	78019265
ENSE00000986168	78025622	78025759
ENSE00000986169	78024971	78025142
ENSE00000986171	78022145	78022384
ENSE00000986172	78021860	78022022
ENSE00000986173	78021546	78021682
ENSE00000986178	78009537	78009675
ENSE00000986182	78000976	78001094
ENSE00000986183	77999981	78000118
ENSE00000986187	77985903	77985985
ENSE00001092878	78026094	78026229
ENSE00001092882	77985170	77985340
ENSE00001092891	78024549	78024703
ENSE00001457628	77975149	77977626
ENSE00001457649	78029364	78029515
ENSE00003290684	78010471	78010540
ENSE00003330153	78013650	78013790
ENSE00003416948	78009864	78009991
ENSE00003475872	78017575	78017716
ENSE00003508805	78007702	78007866
ENSE00003628599	78002197	78002308
ENSE00003676833	78004716	78004888
ENSE00003974560	77984205	77984298
ENSE00003974566	77983920	77984012
ENSE00003974585	77981428	77981559
ENSE00003974586	77980141	77980273
ENSE00003974587	77993197	77993367
ENSE00003974589	77982154	77982318
ENSE00003974597	77991054	77991167
ENSE00003974600	77982653	77982817
ENSE00003974607	77986073	77986159

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 92.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.4642 / max 153.7318, expressed in 1804 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110209	15.7384	1792
110210	2.7257	1330

Top tissues by expression

251 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	92.39	gold quality
middle temporal gyrus	UBERON:0002771	90.05	gold quality
secondary oocyte	CL:0000655	89.75	gold quality
tibialis anterior	UBERON:0001385	89.02	silver quality
Brodmann (1909) area 23	UBERON:0013554	88.03	gold quality
endothelial cell	CL:0000115	87.70	gold quality
upper arm skin	UBERON:0004263	87.29	silver quality
kidney epithelium	UBERON:0004819	86.94	silver quality
cortical plate	UBERON:0005343	86.83	gold quality
oocyte	CL:0000023	86.02	gold quality
superior frontal gyrus	UBERON:0002661	85.73	gold quality
parietal lobe	UBERON:0001872	85.27	gold quality
postcentral gyrus	UBERON:0002581	85.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.93	gold quality
cerebellar vermis	UBERON:0004720	84.71	gold quality
entorhinal cortex	UBERON:0002728	84.29	gold quality
deltoid	UBERON:0001476	84.24	silver quality
ganglionic eminence	UBERON:0004023	83.57	gold quality
stromal cell of endometrium	CL:0002255	83.50	gold quality
primary visual cortex	UBERON:0002436	83.47	gold quality
occipital lobe	UBERON:0002021	83.41	gold quality
nipple	UBERON:0002030	83.30	gold quality
gastrocnemius	UBERON:0001388	82.86	gold quality
islet of Langerhans	UBERON:0000006	82.76	gold quality
muscle of leg	UBERON:0001383	82.60	gold quality
prefrontal cortex	UBERON:0000451	82.55	gold quality
epithelial cell of pancreas	CL:0000083	82.52	gold quality
Brodmann (1909) area 46	UBERON:0006483	82.49	gold quality
frontal cortex	UBERON:0001870	82.41	gold quality
quadriceps femoris	UBERON:0001377	82.25	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.11
E-MTAB-6386	no	516.89
E-GEOD-124858	no	222.96

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

74 targeting POLR3A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-3151-5P	99.86	63.83	1069

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy. (PMID:21855841)
• Mutations in POLR3A and POLR3B encoding RNA Polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy (PMID:22036171)
• Studies indicate that aatients with anti-RNAP have an increased risk of malignancy within a 5-year timeframe before or after onset of systemic sclerosis (SSc) skin changes. (PMID:22189167)
• Investigated POLR3A and POLR3B mutations in patients with genetically unexplained hypomyelinating leukodystrophies with features of Pol III-related leukodystrophies. Recessive mutations in POLR3A or POLR3B were uncovered in all 14 patients. (PMID:23355746)
• MRI in patients with POLR3B mutations revealed smaller cerebellar structures, especially vermis, than those in POLR3A mutations. MRI also showed milder hypomyelination in patients with POLR3B mutations than those with POLR3A mutations (PMID:23643445)
• Mutations in POLR3A are associated with a more severe clinical course of 4H leukodystrophy. (PMID:25339210)
• Mutations in POLR3A or POLR3B are rare in patients with unclassified hypomyelination. (PMID:26011300)
• Multicenter retrospective study to collect neuroradiologic, clinical, and molecular data of patients with mutations in POLR3A and POLR3B without the classic MRI phenotype: diffuse hypomyelination is not an obligatory feature of POLR3-related disorders; two distinct patterns, selective involvement of the corticospinal tracts and cerebellar atrophy, are added to the MRI presentation of POLR3-related disorders (PMID:27029625)
• For some of its complex functions, variation in RNAP III activity levels lead to nonuniform changes in tRNA pools that can shift the translation profiles of key codon-biased mRNAs with resultant phenotypes or disease states. (Review) (PMID:27068803)
• Our transcriptome-wide investigations revealed an overall decrease in the levels of Pol III-transcribed tRNAs and an imbalance in the levels of regulatory ncRNAs such as small nuclear and nucleolar RNAs (snRNAs and snoRNAs). (PMID:27506977)
• This is the first individual reported with two truncating POLR3A variants, suggesting that biallelic severe loss of function variants are associated with WRS. Sequencing of POLR3A and perhaps related genes such as POLR3B in additional patients with clinical findings of WRS is needed to prove this gene-disease association. (PMID:27612211)
• RNA polymerase III (RNAPIII) is specialized for transcription of short, abundant nonprotein-coding RNA transcripts. (PMID:27911719)
• the first transgenic mice with a leukodystrophy-causing Polr3a mutation do not recapitulate the childhood-onset hypomyelinating leukodystrophy observed in the majority of human patients with POLR3A mutations. (PMID:28407788)
• Mutations in POLR3A are a frequent cause of sporadic and recessive spastic ataxia. (PMID:28459997)
• Findings suggest that AP-1 factors are regulators of RNA polymerase III (Pol III)-driven 5S rRNA and U6 snRNA expression with a potential role in cell proliferation. (PMID:28488757)
• monogenic or digenic POLR3A and POLR3C deficiencies confer increased susceptibility to severe VZV disease in otherwise healthy children, providing evidence for an essential role of a DNA sensor in human immunity (PMID:28783042)
• RNA polymerase III (Pol III) transcribes medium-sized non-coding RNAs (collectively termed Pol III genes), and data show that when Pol III genes are hypo-methylated, MYC amplifies their transcription, regardless of its recognition DNA motif. (PMID:28846112)
• Mutations in the coding region of POLR3A cause impaired expression of antiviral cytokines and susceptibility to varicella-zoster virus CNS infection. (PMID:29728610)
• Here, the authors identified multiple RNA regions in Kaposi’s sarcoma-associated herpesvirus as potential virus ligands that bind to RIG-I and stimulate RIG-I-dependent but RNA Pol III-independent IFN-beta signaling. (PMID:29970461)
• RNA polymerase III is a gatekeeper to prevent severe Varicella Zoster virus infections. (Review) (PMID:30115567)
• Biallelic mutations in POLR3A, which encodes for the largest subunit of the DNA-dependent RNA polymerase III, underlie WRS. No isolated functional sites in POLR3A explain the phenotype variability in POLR3A-related disorders. We suggest that specific combinations of compound heterozygous variants must be present to cause the WRS phenotype. (PMID:30323018)
• The association of bi-allelic POLR3A variants with WRS. (PMID:30414627)
• we firmly establish biallelic mutations in POLR3A as the genetic cause of a recognizable, neonatal, Wiedemann-Rautenstrauch-like progeroid syndrome. Thus, we suggest that POLR3A mutations are causal for a portion of under-diagnosed early-onset segmental progeroid syndromes (PMID:30450527)
• Of the 8 previously reported WRS-affected individuals at University of Texas Southwestern, 2 of them had bi-allelic POLR3A variants and 2 others each had de novo variants in FBN1 and CAV1, but the genetic basis for the disorder found in the other 2 remains unclear. At Washington University, all 5 WRS-affected individuals had bi-allelic POLR3A variants. (PMID:30690919)
• findings provide the first evidence for impaired Pol III transcription in cellular models of POLR3-HLD and identify several candidate effectors, including BC200 RNA, having a potential role in oligodendrocyte biology and involvement in the disease (PMID:30898877)
• Novel mutations of the POLR3A gene caused POLR3-related leukodystrophy in a Chinese family: a case report. (PMID:31438894)
• POLR3A-related spastic ataxia: new mutations and a look into the phenotype. (PMID:31637490)
• POLR3A variants with striatal involvement and extrapyramidal movement disorder. (PMID:31940116)
• Structural basis for RNA polymerase III transcription repression by Maf1 in humans and yeast has been uncovered. (PMID:32066962)
• Runx2 mediates the deregulation of Brf1 and Pol III genes and its abnormal expression predicts the worse prognosis of breast cancer. (PMID:32198086)
• Identification of a deep intronic POLR3A variant causing inclusion of a pseudoexon derived from an Alu element in Pol III-related leukodystrophy. (PMID:32483275)
• Estimating the relative frequency of leukodystrophies and recommendations for carrier screening in the era of next-generation sequencing. (PMID:32573057)
• A novel POLR3A genotype leads to leukodystrophy type-7 in two siblings with unusually late age of onset. (PMID:32600288)
• Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C. (PMID:33005949)
• Functional characterization of Polr3a hypomyelinating leukodystrophy mutations in the S. cerevisiae homolog, RPC160. (PMID:33148458)
• Two intronic cis-acting variants in both alleles of the POLR3A gene cause progressive spastic ataxia with hypodontia. (PMID:33491183)
• Wiedemann-Rautenstrauch syndrome in an Indian patient with biallelic pathogenic variants in POLR3A. (PMID:33559318)
• RNA polymerase III is required for the repair of DNA double-strand breaks by homologous recombination. (PMID:33626331)
• POLR3A variants in hereditary spastic paraparesis and ataxia: clinical, genetic, and neuroradiological findings in a cohort of Italian patients. (PMID:34296356)
• Distinguishing severe phenotypes associated with pathogenic variants in POLR3A. (PMID:34773388)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	polr3a	ENSDARG00000102569
mus_musculus	Polr3a	ENSMUSG00000025280
rattus_norvegicus	Polr3a	ENSRNOG00000010008
drosophila_melanogaster	Polr3A	FBGN0030687
caenorhabditis_elegans		WBGENE00004411

Paralogs (2): POLR1A (ENSG00000068654), POLR2A (ENSG00000181222)

Protein

Protein identifiers

DNA-directed RNA polymerase III subunit RPC1 — O14802 (reviewed: O14802)

Alternative names: DNA-directed RNA polymerase III largest subunit, DNA-directed RNA polymerase III subunit A, RNA polymerase III 155 kDa subunit, RNA polymerase III subunit C160

All UniProt accessions (6): O14802, A0A8V8TM36, A0A8V8TM70, A0A8V8TNL6, A0A8V8TNX3, R4GMX2

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic core component of RNA polymerase III (Pol III), a DNA-dependent RNA polymerase which synthesizes small non-coding RNAs using the four ribonucleoside triphosphates as substrates. Synthesizes 5S rRNA, snRNAs, tRNAs and miRNAs from at least 500 distinct genomic loci. Pol III-mediated transcription cycle proceeds through transcription initiation, transcription elongation and transcription termination stages. During transcription initiation, Pol III is recruited to DNA promoters type I, II or III with the help of general transcription factors and other specific initiation factors. Once the polymerase has escaped from the promoter it enters the elongation phase during which RNA is actively polymerized, based on complementarity with the template DNA strand. Transcription termination involves the release of the RNA transcript and polymerase from the DNA. Forms Pol III active center together with the second largest subunit POLR3B/RPC2. Appends one nucleotide at a time to the 3’ end of the nascent RNA, with POLR3A/RPC1 contributing a Mg(2+)-coordinating DxDGD motif, and POLR3B/RPC2 participating in the coordination of a second Mg(2+) ion and providing lysine residues believed to facilitate Watson-Crick base pairing between the incoming nucleotide and template base. Typically, Mg(2+) ions direct a 5’ nucleoside triphosphate to form a phosphodiester bond with the 3’ hydroxyl of the preceding nucleotide of the nascent RNA, with the elimination of pyrophosphate. Pol III plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as a nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts, such as Epstein-Barr virus-encoded RNAs (EBERs) induce type I interferon and NF-kappa-B through the RIG-I pathway.

Subunit / interactions. Component of the RNA polymerase III (Pol III) (Pol III) complex consisting of 17 subunits: a ten-subunit catalytic core composed of POLR3A/RPC1, POLR3B/RPC2, POLR1C/RPAC1, POLR1D/RPAC2, POLR3K/RPC10, POLR2E/RPABC1, POLR2F/RPABC2, POLR2H/RPABC3, POLR2K/RPABC4 and POLR2L/RPABC5; a mobile stalk composed of two subunits POLR3H/RPC8 and CRCP/RPC9, protruding from the core and functioning primarily in transcription initiation; and additional subunits homologous to general transcription factors of the RNA polymerase II machinery, POLR3C/RPC3-POLR3F/RPC6-POLR3G/RPC7 heterotrimer required for transcription initiation and POLR3D/RPC4-POLR3E/RPC5 heterodimer involved in both transcription initiation and termination. Pol III exists as two alternative complexes defined by the mutually exclusive incorporation of subunit POLR3G/RPC7alpha or POLR3GL/RPC7beta. The presence of POLR3G/RPC7alpha or POLR3GL/RPC7beta differentially modulates the transcription potential of Pol III, with POLR3G/RPC7alpha specifically associated with transcription of snaR-A non-coding RNAs. As part of the RNA polymerase III complex, interacts with PKP2.

Subcellular location. Nucleus. Cytoplasm. Cytosol.

Tissue specificity. Expressed in the brain, in the cortex and the white matter (at protein level).

Disease relevance. Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism (HLD7) [MIM:607694] An autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive motor decline manifest as spasticity, ataxia, tremor, and cerebellar signs, as well as mild cognitive regression. Other features may include hypodontia or oligodontia and hypogonadotropic hypogonadism. There is considerable inter- and intrafamilial variability. The disease is caused by variants affecting the gene represented in this entry. Wiedemann-Rautenstrauch syndrome (WDRTS) [MIM:264090] An autosomal recessive, neonatal progeroid disorder characterized by intrauterine growth retardation, failure to thrive, short stature, hypotonia, variable mental impairment, and a progeroid appearance. Clinical features include apparent macrocephaly, sparse hair, prominent scalp veins, entropion, greatly widened anterior fontanelles, malar hypoplasia, and generalized lipoatrophy. Death usually occurs in early childhood but survival to third decade has been reported. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Two Mg(2+) ions are coordinated by both the catalytic residues and the nucleic acid substrate to enhance substrate recognition and catalytic efficiency.

Similarity. Belongs to the RNA polymerase beta’ chain family.

RefSeq proteins (1): NP_008986* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000722	RNA_pol_asu	Domain
IPR006592	RNA_pol_N	Domain
IPR007066	RNA_pol_Rpb1_3	Domain
IPR007080	RNA_pol_Rpb1_1	Domain
IPR007081	RNA_pol_Rpb1_5	Domain
IPR007083	RNA_pol_Rpb1_4	Domain
IPR015700	RPC1	Family
IPR035697	RNAP_III_RPC1_N	Domain
IPR035698	RNAP_III_Rpc1_C	Domain
IPR038120	Rpb1_funnel_sf	Homologous_superfamily
IPR042102	RNA_pol_Rpb1_3_sf	Homologous_superfamily
IPR044893	RNA_pol_Rpb1_clamp_domain	Homologous_superfamily

Pfam: PF00623, PF04983, PF04997, PF04998, PF05000

Catalyzed reactions (Rhea), 1 shown:

• RNA(n) + a ribonucleoside 5’-triphosphate = RNA(n+1) + diphosphate (RHEA:21248)

UniProt features (210 total): helix 66, strand 63, sequence variant 27, binding site 25, turn 20, sequence conflict 5, region of interest 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
7AE1	ELECTRON MICROSCOPY	2.8
9K39	ELECTRON MICROSCOPY	2.8
7D58	ELECTRON MICROSCOPY	2.9
9K36	ELECTRON MICROSCOPY	2.9
9K2G	ELECTRON MICROSCOPY	3
9K3U	ELECTRON MICROSCOPY	3
7AE3	ELECTRON MICROSCOPY	3.1
7D59	ELECTRON MICROSCOPY	3.1
9K38	ELECTRON MICROSCOPY	3.1
9FSO	ELECTRON MICROSCOPY	3.28
7A6H	ELECTRON MICROSCOPY	3.3
9LXN	ELECTRON MICROSCOPY	3.3
7DU2	ELECTRON MICROSCOPY	3.35
9FSP	ELECTRON MICROSCOPY	3.39
7AEA	ELECTRON MICROSCOPY	3.4
8IUH	ELECTRON MICROSCOPY	3.4
7DN3	ELECTRON MICROSCOPY	3.5
9K3V	ELECTRON MICROSCOPY	3.5
9LKT	ELECTRON MICROSCOPY	3.5
9FSQ	ELECTRON MICROSCOPY	3.51
7FJI	ELECTRON MICROSCOPY	3.6
7FJJ	ELECTRON MICROSCOPY	3.6
9LXO	ELECTRON MICROSCOPY	3.6
9FSR	ELECTRON MICROSCOPY	3.76
8ITY	ELECTRON MICROSCOPY	3.9
7AST	ELECTRON MICROSCOPY	4
8IUE	ELECTRON MICROSCOPY	4.1
9FSS	ELECTRON MICROSCOPY	4.14
9K3B	ELECTRON MICROSCOPY	4.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14802-F1	88.40	0.57

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (25): 156; 159; 167; 326; 348; 353; 360; 366; 464; 499; 499; 501 …

Post-translational modifications (1): 445

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-1834949	Cytosolic sensors of pathogen-associated DNA
R-HSA-73780	RNA Polymerase III Chain Elongation
R-HSA-73980	RNA Polymerase III Transcription Termination
R-HSA-749476	RNA Polymerase III Abortive And Retractive Initiation
R-HSA-76061	RNA Polymerase III Transcription Initiation From Type 1 Promoter
R-HSA-76066	RNA Polymerase III Transcription Initiation From Type 2 Promoter
R-HSA-76071	RNA Polymerase III Transcription Initiation From Type 3 Promoter
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-74158	RNA Polymerase III Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-76046	RNA Polymerase III Transcription Initiation

MSigDB gene sets: 599 (showing top): REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_INITIATION_FROM_TYPE_3_PROMOTER, REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_TERMINATION, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_RNA_POLYMERASE_III_CHAIN_ELONGATION, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, KEGG_CYTOSOLIC_DNA_SENSING_PATHWAY, MARTINEZ_RB1_TARGETS_UP, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_POSITIVE_REGULATION_OF_INTERFERON_BETA_PRODUCTION

GO Biological Process (7): DNA-templated transcription (GO:0006351), positive regulation of interferon-beta production (GO:0032728), tRNA transcription by RNA polymerase III (GO:0042797), innate immune response (GO:0045087), defense response to virus (GO:0051607), immune system process (GO:0002376), positive regulation of gene expression (GO:0010628)

GO Molecular Function (11): magnesium ion binding (GO:0000287), DNA binding (GO:0003677), chromatin binding (GO:0003682), DNA-directed RNA polymerase activity (GO:0003899), zinc ion binding (GO:0008270), DNA/RNA hybrid binding (GO:0071667), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779), 5’-3’ RNA polymerase activity (GO:0034062), metal ion binding (GO:0046872)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), RNA polymerase III complex (GO:0005666), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), DNA-directed RNA polymerase complex (GO:0000428), nuclear lumen (GO:0031981)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
RNA Polymerase III Transcription	4
RNA Polymerase III Transcription Initiation	3
Innate Immune System	1
Immune System	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
gene expression	2
RNA biosynthetic process	2
nucleic acid binding	2
binding	2
positive regulation of type I interferon production	1
interferon-beta production	1
regulation of interferon-beta production	1
transcription by RNA polymerase III	1
tRNA transcription	1
immune response	1
defense response to symbiont	1
defense response	1
response to virus	1
biological_process	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
metal ion binding	1
5’-3’ RNA polymerase activity	1
transition metal ion binding	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
RNA polymerase activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
DNA-directed RNA polymerase complex	1
nuclear protein-containing complex	1
intracellular anatomical structure	1
cytoplasm	1
RNA polymerase complex	1
nucleus	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

4398 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLR3A	POLR3B	Q9NW08	976
POLR3A	POLR1D	P0DPB6	925
POLR3A	MAF1	Q9H063	906
POLR3A	BDP1	A6H8Y1	902
POLR3A	POLR3K	Q9Y2Y1	866
POLR3A	POLR3C	Q9BUI4	862
POLR3A	POLR3F	Q9H1D9	846
POLR3A	POLR3G	O15318	831
POLR3A	POLR3E	Q9NVU0	813
POLR3A	POLR3GL	Q9BT43	811
POLR3A	POLI	Q9UNA4	787
POLR3A	POLR3H	Q9Y535	782
POLR3A	POLR3D	P05423	762
POLR3A	POLR2E	P19388	719
POLR3A	GTF3C2	Q8WUA4	689

IntAct

197 interactions, top by confidence:

A	B	Type	Score
POLR2E	POLR3A	psi-mi:“MI:0914”(association)	0.870
POLR2E	POLR3A	psi-mi:“MI:0915”(physical association)	0.870
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
POLR3GL	POLR3A	psi-mi:“MI:0914”(association)	0.730
POLR2E	MED19	psi-mi:“MI:0914”(association)	0.730
POLR3E	POLR3A	psi-mi:“MI:0914”(association)	0.730
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
PPP1CA	CCDC85C	psi-mi:“MI:2364”(proximity)	0.670
PFDN2	POLR3A	psi-mi:“MI:0914”(association)	0.670
POLR3A	PFDN2	psi-mi:“MI:0915”(physical association)	0.670
PTGES3	POLR3A	psi-mi:“MI:0915”(physical association)	0.670
POLR3D	POLR3A	psi-mi:“MI:0914”(association)	0.640
RUVBL2	POLR3A	psi-mi:“MI:0914”(association)	0.640
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
POLR3K	POLR3A	psi-mi:“MI:0914”(association)	0.640
POLR2F	POLR3A	psi-mi:“MI:0914”(association)	0.640

BioGRID (320): POLR3A (Affinity Capture-MS), POLR3A (Affinity Capture-MS), POLR3A (Affinity Capture-MS), POLR3A (Affinity Capture-MS), POLR3A (Affinity Capture-MS), POLR3A (Affinity Capture-MS), POLR3A (Affinity Capture-MS), POLR3A (Affinity Capture-MS), POLR3A (Affinity Capture-MS), CRCP (Co-fractionation), GTF3C3 (Co-fractionation), HDAC1 (Co-fractionation), HDAC2 (Co-fractionation), IPO9 (Co-fractionation), MRPL17 (Co-fractionation)

ESM2 similar proteins: A4IF62, A5CC92, A8EXK9, A8F0P8, A8GMA8, A8GQW5, A8GV25, B0BWB0, B3CV54, F4JXF9, O14802, O55766, O94666, P04050, P04051, P08968, P0C987, P0C988, P0C989, P10964, P15398, P17545, P17546, P28364, P42486, P91875, Q07KK8, Q11HB4, Q196X0, Q1LSX6, Q1RHD1, Q211D9, Q2GFP4, Q2GJ69, Q3YST4, Q4FLL3, Q4UKD5, Q5FFD8, Q5HC04, Q5ZL98

Diamond homologs: A0PXT9, A2RML8, A3CKD4, A4FWF5, A4IF62, A4YCR0, A5CUC6, A5DCV3, A6UV49, A6VGV0, A8AZI2, A8F4G1, A9A9U9, A9BCH4, B0R8D3, B0RB26, B4U738, B6YT17, B8YB54, C0ZVQ7, C1AYV8, C3MRK4, C3MYA0, C3MZM9, C3N7Q1, C3NFS2, C4KIV9, C5A207, F4JXF9, G3MZY8, O14802, O27126, O28390, O35134, O54889, O93777, O94666, O95602, P04050, P04051

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
POLR3A	up-regulates	Viral_dsRNA
“Cytosolic DNA”	up-regulates	POLR3A
POLR3A	“form complex”	“RNA Polymerase III”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 131 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RNA Polymerase III Chain Elongation	16	120.8×	8e-31
RNA Polymerase III Transcription Termination	16	94.6×	3e-28
RNA Polymerase III Transcription Initiation From Type 2 Promoter	18	90.6×	8e-31
RNA Polymerase III Transcription Initiation From Type 1 Promoter	18	87.4×	1e-30
RNA Polymerase III Transcription Initiation From Type 3 Promoter	18	87.4×	1e-30
RNA Polymerase III Transcription Initiation	18	72.0×	1e-28
RNA Polymerase III Transcription	18	69.9×	2e-28
RNA Polymerase III Abortive And Retractive Initiation	18	59.7×	8e-27

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase III	8	53.3×	8e-10
positive regulation of innate immune response	5	22.9×	5e-04
positive regulation of interferon-beta production	5	17.0×	1e-03
protein stabilization	12	7.0×	6e-05
transcription by RNA polymerase II	10	6.1×	8e-04
defense response to virus	10	6.0×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

1241 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	51
Likely pathogenic	50
Uncertain significance	448
Likely benign	454
Benign	81

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027476	NM_007055.4(POLR3A):c.3839dup (p.Met1280fs)	Pathogenic
1030186	NM_007055.4(POLR3A):c.3733C>T (p.Arg1245Ter)	Pathogenic
1034345	NM_007055.4(POLR3A):c.2323_2329del (p.Asn775fs)	Pathogenic
1184058	NM_007055.4(POLR3A):c.441dup (p.Asp148Ter)	Pathogenic
1323485	NM_007055.4(POLR3A):c.1229dup (p.Asn410fs)	Pathogenic
1374074	NM_007055.4(POLR3A):c.2257_2278dup (p.Arg760fs)	Pathogenic
1427214	NM_007055.4(POLR3A):c.2658T>A (p.Tyr886Ter)	Pathogenic
1440437	NM_007055.4(POLR3A):c.112del (p.Ser38fs)	Pathogenic
1449664	NM_007055.4(POLR3A):c.1608dup (p.Pro537fs)	Pathogenic
1455738	NM_007055.4(POLR3A):c.2163C>A (p.Tyr721Ter)	Pathogenic
1456249	NC_000010.10:g.(?79780889)(79784717_?)del	Pathogenic
1460249	NC_000010.10:g.(?79781284)(79782162_?)del	Pathogenic
1879069	NM_007055.4(POLR3A):c.646-665_1185+867del	Pathogenic
1903818	NM_007055.4(POLR3A):c.3951dup (p.Leu1318fs)	Pathogenic
1928113	NM_007055.4(POLR3A):c.2631_2640del (p.Ser878fs)	Pathogenic
1975923	NM_007055.4(POLR3A):c.685C>T (p.Arg229Ter)	Pathogenic
2017609	NM_007055.4(POLR3A):c.2176G>T (p.Glu726Ter)	Pathogenic
2086772	NM_007055.4(POLR3A):c.2360_2364dup (p.Phe789fs)	Pathogenic
2136897	NM_007055.4(POLR3A):c.2671C>T (p.Arg891Ter)	Pathogenic
235466	NM_007055.4(POLR3A):c.2617C>T (p.Arg873Ter)	Pathogenic
2412670	NM_007055.4(POLR3A):c.3115C>T (p.Gln1039Ter)	Pathogenic
2425680	NC_000010.10:g.(?79767440)(79770318_?)del	Pathogenic
2425681	NC_000010.10:g.(?79737218)(79745937_?)del	Pathogenic
2691390	NC_000010.10:g.(79779024_79781303)_(79782143_79784306)del	Pathogenic
2742457	NM_007055.4(POLR3A):c.2344del (p.Leu782fs)	Pathogenic
280427	NM_007055.4(POLR3A):c.491-2A>G	Pathogenic
2842195	NM_007055.4(POLR3A):c.1325_1326del (p.Gln442fs)	Pathogenic
2996417	NM_007055.4(POLR3A):c.1738A>T (p.Lys580Ter)	Pathogenic
3018940	NM_007055.4(POLR3A):c.1784G>A (p.Trp595Ter)	Pathogenic
31147	NM_007055.4(POLR3A):c.418C>T (p.Arg140Ter)	Pathogenic

SpliceAI

4107 predictions. Top by Δscore:

Variant	Effect	Δscore
10:77980140:CCA:C	donor_gain	1.0000
10:77980140:CCACA:C	donor_gain	1.0000
10:77980270:CACC:C	acceptor_gain	1.0000
10:77980274:C:CC	acceptor_gain	1.0000
10:77980274:CT:C	acceptor_loss	1.0000
10:77980280:C:CT	acceptor_gain	1.0000
10:77981424:ATACC:A	donor_loss	1.0000
10:77981425:TACCT:T	donor_loss	1.0000
10:77981426:A:AC	donor_gain	1.0000
10:77981427:C:CC	donor_gain	1.0000
10:77981556:CCAC:C	acceptor_gain	1.0000
10:77981557:CAC:C	acceptor_gain	1.0000
10:77981557:CACC:C	acceptor_gain	1.0000
10:77981560:C:CC	acceptor_gain	1.0000
10:77981561:T:C	acceptor_loss	1.0000
10:77981563:C:CT	acceptor_gain	1.0000
10:77982315:CCAC:C	acceptor_gain	1.0000
10:77982316:CACC:C	acceptor_gain	1.0000
10:77982584:AGGTC:A	donor_gain	1.0000
10:77982643:T:TA	donor_gain	1.0000
10:77983891:T:TA	donor_gain	1.0000
10:77983914:ACT:A	donor_loss	1.0000
10:77983915:CT:C	donor_loss	1.0000
10:77983916:TCACT:T	donor_loss	1.0000
10:77983917:CAC:C	donor_loss	1.0000
10:77983918:A:AC	donor_gain	1.0000
10:77983918:A:C	donor_loss	1.0000
10:77983918:ACTT:A	donor_gain	1.0000
10:77983919:C:CT	donor_gain	1.0000
10:77983919:CTT:C	donor_gain	1.0000

AlphaMissense

9194 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:77977584:C:T	G1356E	1.000
10:77977585:C:G	G1356R	1.000
10:77977585:C:T	G1356R	1.000
10:77977602:C:A	G1350V	1.000
10:77977602:C:T	G1350E	1.000
10:77977603:C:G	G1350R	1.000
10:77977603:C:T	G1350R	1.000
10:77977608:A:T	I1348N	1.000
10:77977620:G:A	S1344F	1.000
10:77977620:G:T	S1344Y	1.000
10:77977626:C:T	G1342E	1.000
10:77980153:C:G	D1338H	1.000
10:77980174:C:G	A1331P	1.000
10:77980182:A:G	L1328P	1.000
10:77980182:A:T	L1328H	1.000
10:77980199:C:A	E1322D	1.000
10:77980199:C:G	E1322D	1.000
10:77980200:T:A	E1322V	1.000
10:77980200:T:G	E1322A	1.000
10:77980201:C:T	E1322K	1.000
10:77980202:A:C	F1321L	1.000
10:77980202:A:T	F1321L	1.000
10:77980203:A:C	F1321C	1.000
10:77980203:A:G	F1321S	1.000
10:77980204:A:C	F1321V	1.000
10:77980204:A:G	F1321L	1.000
10:77980204:A:T	F1321I	1.000
10:77980206:G:A	S1320F	1.000
10:77980206:G:T	S1320Y	1.000
10:77980207:A:G	S1320P	1.000

dbSNP variants (sampled 300 via entrez): RS1000106977 (10:77996935 C>A,T), RS1000132723 (10:77984964 C>T), RS1000139523 (10:77997249 C>T), RS1000185114 (10:77988161 G>A), RS1000216070 (10:77988471 G>A), RS1000264122 (10:78031236 T>G), RS1000320088 (10:77991507 C>T), RS1000349025 (10:78018361 T>C), RS1000399968 (10:77979780 C>T), RS1000412455 (10:77985555 C>G), RS1000493506 (10:77994651 T>C), RS1000649307 (10:77991132 G>A,C), RS1000684935 (10:78007464 A>T), RS1000761454 (10:77979560 G>A,C,T), RS1000774156 (10:77999705 A>G,T)

Disease associations

OMIM: gene MIM:614258 | disease phenotypes: MIM:264090, MIM:607694, MIM:312080, MIM:213002, MIM:614381, MIM:108600, MIM:612233

GenCC curated gene-disease

Disease	Classification	Inheritance
odontoleukodystrophy	Definitive	Autosomal recessive
Wiedemann-Rautenstrauch syndrome	Definitive	Autosomal recessive
leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism	Strong	Autosomal recessive
POLR3A-related disorder	Strong	Autosomal recessive
varicella zoster infection	Moderate	Autosomal dominant
hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome	Supportive	Autosomal recessive
tremor-ataxia-central hypomyelination syndrome	Supportive	Autosomal recessive
hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
POLR3A-related disorder	Definitive	AR

Mondo (16): Wiedemann-Rautenstrauch syndrome (MONDO:0009910), leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism (MONDO:0011897), leukodystrophy (MONDO:0019046), POLR3A-related disorder (MONDO:0700276), POLR-related leukodystrophy (MONDO:0100605), movement disorder (MONDO:0005395), hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism (MONDO:0013722), spastic ataxia (MONDO:0017845), hereditary ataxia (MONDO:0100309), intellectual disability (MONDO:0001071), hypomyelinating leukodystrophy 4 (MONDO:0012824), odontoleukodystrophy (MONDO:0019177), hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome (MONDO:0018655), tremor-ataxia-central hypomyelination syndrome (MONDO:0018656), (MONDO:0019505)

Orphanet (14): Wiedemann-Rautenstrauch syndrome (Orphanet:3455), Hypomyelinating leukodystrophy-ataxia-hypodontia-hypomyelination syndrome (Orphanet:137639), Hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome (Orphanet:447893), Tremor-ataxia-central hypomyelination syndrome (Orphanet:447896), Odontoleukodystrophy (Orphanet:77295), Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome (Orphanet:88637), Leukodystrophy (Orphanet:68356), 4H leukodystrophy (Orphanet:289494), Hereditary ataxia (Orphanet:183518), Spastic ataxia (Orphanet:316226), Endosteal sclerosis-cerebellar hypoplasia syndrome (Orphanet:85186), Pelizaeus-Merzbacher-like disease (Orphanet:280270), Pelizaeus-Merzbacher-like disease due to HSPD1 mutation (Orphanet:280288), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

224 total (30 of 224 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000028	Cryptorchidism
HP:0000040	Long penis
HP:0000044	Hypogonadotropic hypogonadism
HP:0000047	Hypospadias
HP:0000076	Vesicoureteral reflux
HP:0000126	Hydronephrosis
HP:0000160	Narrow mouth
HP:0000164	Abnormality of the dentition
HP:0000219	Thin upper lip vermilion
HP:0000233	Thin vermilion border
HP:0000238	Hydrocephalus
HP:0000242	Parietal bossing
HP:0000248	Brachycephaly
HP:0000256	Macrocephaly
HP:0000267	Cranial asymmetry
HP:0000272	Malar flattening
HP:0000278	Retrognathia
HP:0000292	Loss of facial adipose tissue
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000336	Prominent supraorbital ridges
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007694_1	Executive function (trail making test B)	7.000000e-06
GCST007856_37	Colorectal cancer or advanced adenoma	5.000000e-18
GCST007856_59	Colorectal cancer or advanced adenoma	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009332	executive function measurement

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009069	Movement Disorders	C10.228.662
C535353	Cerebellar hypoplasia with endosteal sclerosis (supp.)
C531684	Hereditary spinal ataxia (supp.)
C567390	Leukodystrophy, Hypomyelinating, 4 (supp.)
C536423	Progeroid syndrome, neonatal (supp.)
C564815	Spastic Ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4665582 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
aristolochic acid I	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Carbamazepine	affects expression	1
Diclofenac	affects expression	1
Estradiol	increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1

Cellosaurus cell lines

10 cell lines: 7 induced pluripotent stem cell, 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A5L0	SEES3-1V human POLR3A, clone1	Embryonic stem cell	Male
CVCL_A5L1	SEES3-1V human POLR3A, clone2	Embryonic stem cell	Male
CVCL_A5L2	SEES3-1V human POLR3A, clone3	Embryonic stem cell	Male
CVCL_A8NN	VUi027-A	Induced pluripotent stem cell	Female
CVCL_A8NQ	VUi029-A	Induced pluripotent stem cell	Male
CVCL_A8NR	VUi030-A	Induced pluripotent stem cell	Female
CVCL_D6ID	HIHRSi004-A	Induced pluripotent stem cell	Male
CVCL_D6IE	HIHRSi005-A	Induced pluripotent stem cell	Male
CVCL_D6IF	HIHRSi006-A	Induced pluripotent stem cell	Male
CVCL_D6R4	CSSi018-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

306 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01682109	PHASE4	COMPLETED	Palatability Testing of a New Paediatric Formulation of Valacyclovir
NCT04403139	PHASE4	ACTIVE_NOT_RECRUITING	VZV-specific Tissue Resident Memory T-cells After Shingrix Vaccination
NCT01662414	PHASE4	COMPLETED	Effect of Undenatured Cysteine-Rich Whey Protein Isolate (HMS 90®) in Patients With Parkinson’s Disease
NCT04871464	PHASE4	UNKNOWN	Role and Mechanism of Probiotics in Improving Motor Symptoms in Mild to Moderate Parkinson’s Disease
NCT06710574	PHASE4	RECRUITING	Multimodal Image Technologies Investigate the Role and Mechanism of Probiotics in Improving RBD with Parkinson’s Disease
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT01838278	PHASE3	UNKNOWN	Effectiveness of Vojta Therapy in Motor Development of Preterm Children
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00001929	PHASE2	COMPLETED	Treatment of Parkinson’s Disease With Eliprodil
NCT00331669	PHASE2	UNKNOWN	Efficacy and Safety of Deep Brain Stimulation (DBS) of the Pallidal (GPi) in Patients With Tardive Dystonia
NCT00406029	PHASE2	COMPLETED	Dyskinesia in Parkinson’s Disease (Study P04501)
NCT00537017	PHASE2	COMPLETED	Follow Up Safety Study of SCH 420814 in Subjects With Parkinson’s Disease (P05175)
NCT00693472	PHASE2	TERMINATED	Study of Preladenant for the Treatment of Neuroleptic Induced Akathisia (Study P05145)
NCT01385592	PHASE2	COMPLETED	Evaluation of the Efficacy and Safety of AFQ056 in Parkinson’s Patients With L-dopa Induced Dyskinesias
NCT01491529	PHASE2	COMPLETED	Evaluation of the Efficacy and Safety of Modified Release AFQ056 in Parkinson’s Patients With L-dopa Induced Dyskinesias
NCT01491932	PHASE2	COMPLETED	Open-label, Long-term Safety Extension Study of AFQ056 in Parkinson’s Patients With L-dopa Induced Dyskinesias
NCT02500628	PHASE2	COMPLETED	Heart Rate Variability in Response to Metformin Challenge
NCT04536987	PHASE2	COMPLETED	Robot Therapy for Rehabilitation of Hand Movement After Stroke
NCT04912115	PHASE2	SUSPENDED	Randomized, Double-Blind, Active Placebo-Controlled Study of Ketamine to Treat Levodopa-Induced Dyskinesia
NCT05636852	PHASE2	TERMINATED	Altropane Dose for Imaging Patients With Suspected Parkinson’s Disease
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
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