POLR3B

Summary

POLR3B (RNA polymerase III subunit B, HGNC:30348) is a protein-coding gene on chromosome 12q23.3, encoding DNA-directed RNA polymerase III subunit RPC2 (Q9NW08). 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 99.4% of cancer cell lines).

This gene encodes the second largest subunit of RNA polymerase III, the polymerase responsible for synthesizing transfer and small ribosomal RNAs in eukaryotes. The largest subunit and the encoded protein form the catalytic center of RNA polymerase III. Mutations in this gene are a cause of hypomyelinating leukodystrophy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 55703 — RefSeq curated summary.

At a glance

• Gene–disease (curated): POLR3B-related disorder (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 683 total — 28 pathogenic, 34 likely-pathogenic
• Phenotypes (HPO): 69
• Cancer dependency (DepMap): dependent in 99.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_018082

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30348
Approved symbol	POLR3B
Name	RNA polymerase III subunit B
Location	12q23.3
Locus type	gene with protein product
Status	Approved
Aliases	RPC2, FLJ10388, C128
Ensembl gene	ENSG00000013503
Ensembl biotype	protein_coding
OMIM	614366
Entrez	55703

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000228347, ENST00000539066, ENST00000549195, ENST00000549569, ENST00000887555, ENST00000887556, ENST00000887557, ENST00000887558, ENST00000887559, ENST00000970164, ENST00000970165

RefSeq mRNA: 2 — MANE Select: NM_018082 NM_001160708, NM_018082

CCDS: CCDS53824, CCDS9105

Canonical transcript exons

ENST00000228347 — 28 exons

Exon	Start	End
ENSE00000754463	106463478	106463620
ENSE00000754474	106501323	106501436
ENSE00000754476	106504081	106504254
ENSE00000818347	106459251	106459368
ENSE00000937915	106457138	106457296
ENSE00000937953	106430273	106430473
ENSE00000937954	106432318	106432480
ENSE00000997847	106427197	106427358
ENSE00000997848	106437057	106437131
ENSE00000997850	106437681	106437779
ENSE00000997851	106433719	106433872
ENSE00000997852	106444463	106444590
ENSE00000997853	106496055	106496158
ENSE00001099347	106380031	106380139
ENSE00001099387	106369583	106369683
ENSE00001099410	106369275	106369350
ENSE00001099422	106378267	106378384
ENSE00001099436	106376359	106376450
ENSE00001099523	106357748	106357951
ENSE00001131116	106496752	106496918
ENSE00001199523	106454502	106454711
ENSE00001286965	106405857	106405976
ENSE00002407950	106509420	106510198
ENSE00003484409	106363870	106363902
ENSE00003534092	106366516	106366572
ENSE00003586604	106410826	106410960
ENSE00003628865	106366658	106366722
ENSE00003693562	106393031	106393153

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 90.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.5869 / max 172.2434, expressed in 1775 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127825	7.8359	1702
127824	2.9659	1454
127826	0.7850	466

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	90.14	gold quality
esophagus squamous epithelium	UBERON:0006920	89.43	gold quality
endothelial cell	CL:0000115	88.11	gold quality
gingival epithelium	UBERON:0001949	87.94	gold quality
squamous epithelium	UBERON:0006914	87.77	gold quality
amniotic fluid	UBERON:0000173	86.88	gold quality
gingiva	UBERON:0001828	86.80	gold quality
epithelium of esophagus	UBERON:0001976	86.78	gold quality
cervix squamous epithelium	UBERON:0006922	86.52	silver quality
hair follicle	UBERON:0002073	84.85	silver quality
nephron tubule	UBERON:0001231	84.06	gold quality
germinal epithelium of ovary	UBERON:0001304	83.65	gold quality
choroid plexus epithelium	UBERON:0003911	83.52	gold quality
tibialis anterior	UBERON:0001385	83.33	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.05	gold quality
placenta	UBERON:0001987	82.74	gold quality
middle temporal gyrus	UBERON:0002771	82.28	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.04	gold quality
upper leg skin	UBERON:0004262	81.82	gold quality
renal glomerulus	UBERON:0000074	81.73	gold quality
metanephric glomerulus	UBERON:0004736	81.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.59	gold quality
oral cavity	UBERON:0000167	81.49	gold quality
parietal pleura	UBERON:0002400	81.42	gold quality
pleura	UBERON:0000977	80.78	gold quality
cranial nerve II	UBERON:0000941	80.24	gold quality
cervix epithelium	UBERON:0004801	80.00	silver quality
sperm	CL:0000019	79.92	silver quality
kidney epithelium	UBERON:0004819	79.59	gold quality
pigmented layer of retina	UBERON:0001782	79.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.26

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

41 targeting POLR3B, 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-4425	100.00	67.59	1049
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-657	99.48	66.02	848
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-150-3P	99.43	70.51	920
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-590-5P	99.25	70.76	930
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-4635	98.74	67.63	1339

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 25)

• Data describe the purification and identification of RNA polymerase III subunits RPC2 and RPC5. (PMID:12391170)
• Results suggest that INMAP is a novel protein that plays essential role in spindle formation and cell-cycle progression. (PMID:19331820)
• Mutations in POLR3A and POLR3B encoding RNA Polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy (PMID:22036171)
• Recessive mutations in POLR3B, encoding the second largest subunit of Pol III, cause a rare hypomyelinating leukodystrophy (PMID:22036172)
• study reports INMAP is a truncated version of POLR3B, and is up-regulated in several human cancer cell lines; results suggest that INMAP may function through the p53 and AP-1 pathways, providing a possible link of its activity with tumourigenesis (PMID:23124897)
• 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)
• INMAP as a model regulator of CENP-B (PMID:24633075)
• Most patients with 4H leukodystrophy carried the common c.1568T>A POLR3B mutation on one allele. (PMID:25339210)
• These results suggest that INMAP might function through p53/p21 pathways. (PMID:25635878)
• Mutations in POLR3A or POLR3B are rare in patients with unclassified hypomyelination. (PMID:26011300)
• first reports of long deletions causing POLR3-related leukodystrophy, suggesting that deletions and duplications in POLR3A or POLR3B should be investigated in patients with a compatible phenotype (PMID:26045207)
• 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)
• The spectrum of phenotypes resulting from POLR3B mutations is wider than previously believed. (PMID:27512013)
• 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)
• Novel compound heterozygous variations in POLR3B were identified in a patient with cerebellar hypoplasia with endosteal sclerosis. (PMID:28589944)
• These results suggest that the deletion of INMAP block the formation of spindle, leading to arrest of cell cycle and DNA damage, finally blocking cell proliferation and inducing apoptosis. (PMID:31405563)
• Three novel mutations of POLR3B c.727A>G (p.Met243Val) and c.2669G>A (p.Arg890His) (P1, P2), and c.1495G>A (p.Met499Val) (P3) were found (PMID:31577365)
• 4H leukodystrophy caused by a homozygous POLR3B mutation: Further delineation of the phenotype. (PMID:32319736)
• Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C. (PMID:33005949)
• De novo variants in POLR3B cause ataxia, spasticity, and demyelinating neuropathy. (PMID:33417887)
• Intellectual disability associated with craniofacial dysmorphism due to POLR3B mutation and defect in spliceosomal machinery. (PMID:35436926)
• Novel de novo POLR3B mutations responsible for demyelinating Charcot-Marie-Tooth disease in Japan. (PMID:35482004)
• Case report: Biallelic variants in POLR3B gene lead to 4H leukodystrophy from the study of brother and sister. (PMID:36042647)
• A novel de novo variant in POLR3B gene associated with a primary axonal involvement of the largest nerve fibers. (PMID:37897416)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	polr3b	ENSDARG00000062915
mus_musculus	Polr3b	ENSMUSG00000034453
rattus_norvegicus	Polr3b	ENSRNOG00000007432
drosophila_melanogaster	Polr3B	FBGN0004463
caenorhabditis_elegans		WBGENE00017300

Paralogs (2): POLR2B (ENSG00000047315), POLR1B (ENSG00000125630)

Protein

Protein identifiers

DNA-directed RNA polymerase III subunit RPC2 — Q9NW08 (reviewed: Q9NW08)

Alternative names: C128, DNA-directed RNA polymerase III 127.6 kDa polypeptide, DNA-directed RNA polymerase III subunit B

All UniProt accessions (2): Q9NW08, F8VRU2

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 largest subunit POLR3A/RPC1. A single-stranded DNA template strand of the promoter is positioned within the central active site cleft of Pol III. 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) 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.

Subcellular location. Nucleus. Cytoplasm. Cytosol.

Disease relevance. Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism (HLD8) [MIM:614381] An autosomal recessive neurodegenerative disorder characterized by early childhood onset of cerebellar ataxia and mild intellectual disabilities associated with diffuse hypomyelination apparent on brain MRI. Variable features include oligodontia and/or hypogonadotropic hypogonadism. The disease is caused by variants affecting the gene represented in this entry. Charcot-Marie-Tooth disease, demyelinating, type 1I (CMT1I) [MIM:619742] An autosomal dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. CMT1I is characterized predominantly by delayed motor development in the first years of life associated with gait abnormalities, sensory ataxia, hyporeflexia, and distal sensory impairment due to a sensorimotor peripheral neuropathy that mainly affects the lower limbs. The disorder is progressive, and some may have upper limb involvement. A subset of patients has central nervous system involvement that manifests as global developmental delay with impaired intellectual development and speech difficulties. 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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NW08-1	1	yes
Q9NW08-2	2

RefSeq proteins (2): NP_001154180, NP_060552* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007120	DNA-dir_RNAP_su2_dom	Domain
IPR007121	RNA_pol_bsu_CS	Conserved_site
IPR007641	RNA_pol_Rpb2_7	Domain
IPR007642	RNA_pol_Rpb2_2	Domain
IPR007644	RNA_pol_bsu_protrusion	Domain
IPR007645	RNA_pol_Rpb2_3	Domain
IPR007646	RNA_pol_Rpb2_4	Domain
IPR007647	RNA_pol_Rpb2_5	Domain
IPR014724	RNA_pol_RPB2_OB-fold	Homologous_superfamily
IPR015712	DNA-dir_RNA_pol_su2	Family
IPR037033	DNA-dir_RNAP_su2_hyb_sf	Homologous_superfamily

Pfam: PF00562, PF04560, PF04561, PF04563, PF04565, PF04566, PF04567

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (175 total): strand 74, helix 41, turn 20, binding site 17, sequence variant 16, sequence conflict 3, chain 1, zinc finger region 1, site 1, splice variant 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-Q9NW08-F1	89.04	0.64

Functional residue map

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

Catalytic / active sites (1): 429 (critical in trapping poly(dt) in pol iii-mediated transcription termination)

Ligand- & substrate-binding residues (17): 904; 1019; 1039; 1040; 1046; 1080; 1083; 1092; 1095; 186; 195; 213 …

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: 297 (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_TRANSCRIPTION_BY_RNA_POLYMERASE_III, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, KEGG_CYTOSOLIC_DNA_SENSING_PATHWAY, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_POSITIVE_REGULATION_OF_INTERFERON_BETA_PRODUCTION, BRN2_01

GO Biological Process (8): positive regulation of interferon-beta production (GO:0032728), snRNA transcription by RNA polymerase III (GO:0042796), innate immune response (GO:0045087), positive regulation of innate immune response (GO:0045089), defense response to virus (GO:0051607), immune system process (GO:0002376), DNA-templated transcription (GO:0006351), transcription by RNA polymerase III (GO:0006383)

GO Molecular Function (9): DNA binding (GO:0003677), DNA-directed RNA polymerase activity (GO:0003899), zinc ion binding (GO:0008270), ribonucleoside binding (GO:0032549), DNA/RNA hybrid binding (GO:0071667), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779), 5’-3’ RNA polymerase activity (GO:0034062), metal ion binding (GO:0046872)

GO Cellular Component (7): nucleoplasm (GO:0005654), RNA polymerase III complex (GO:0005666), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear DNA-directed RNA polymerase complex (GO:0055029), DNA-directed RNA polymerase complex (GO:0000428), nucleus (GO:0005634)

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	3
RNA biosynthetic process	2
nucleic acid binding	2
DNA-directed RNA polymerase complex	2
nuclear protein-containing complex	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
snRNA transcription	1
immune response	1
defense response to symbiont	1
positive regulation of response to biotic stimulus	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
innate immune response	1
regulation of innate immune response	1
positive regulation of immune response	1
defense response	1
response to virus	1
biological_process	1
gene expression	1
DNA-templated transcription	1
5’-3’ RNA polymerase activity	1
transition metal ion binding	1
nucleoside binding	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
RNA polymerase activity	1
cation binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
nucleoplasm	1
RNA polymerase complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

5322 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLR3B	POLR3A	O14802	976
POLR3B	POLR3K	Q9Y2Y1	955
POLR3B	POLR3F	Q9H1D9	874
POLR3B	POLR3G	O15318	852
POLR3B	POLR3H	Q9Y535	816
POLR3B	POLR3C	Q9BUI4	807
POLR3B	POLR3D	P05423	783
POLR3B	POLR3E	Q9NVU0	771
POLR3B	POLR3GL	Q9BT43	738
POLR3B	POLR1D	P0DPB6	729
POLR3B	CRCP	O75575	609
POLR3B	POLR2E	P19388	597
POLR3B	POLR1A	O95602	562
POLR3B	TCP11L2	Q8N4U5	536
POLR3B	MAF1	Q9H063	490

IntAct

119 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
POLR3D	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
POLR2L	POLR3A	psi-mi:“MI:0914”(association)	0.640
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
RPAP3	POLR3A	psi-mi:“MI:0914”(association)	0.560
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
PIH1D1	POLR3A	psi-mi:“MI:0914”(association)	0.530

BioGRID (271): POLR3B (Affinity Capture-RNA), POLR3B (Affinity Capture-RNA), POLR3B (Affinity Capture-MS), POLR3B (Affinity Capture-MS), POLR3B (Affinity Capture-MS), POLR3B (Affinity Capture-MS), POLR3B (Affinity Capture-MS), POLR3B (Affinity Capture-MS), POLR3B (Affinity Capture-MS), CRCP (Co-fractionation), EEF1A1 (Co-fractionation), IPO9 (Co-fractionation), MRPL17 (Co-fractionation), NOB1 (Co-fractionation), POLR1A (Co-fractionation)

ESM2 similar proteins: A0AF63, A1SEK1, A5DHT2, A5PJW8, B3DTE2, B7GUG7, B8DEY8, B9DKV0, C1KYJ3, F4I366, F4KD38, O74633, P08266, P08518, P22138, P22276, P25167, P30876, P38420, P59470, Q02061, Q03587, Q04E85, Q10233, Q10578, Q27493, Q42877, Q49V52, Q4L3K3, Q54BM1, Q54J75, Q5HRL0, Q6FLD5, Q724F0, Q753Q4, Q75DS1, Q82Z40, Q8CFI7, Q8CQ84, Q8ETY8

Diamond homologs: A0LII4, A0M3Y9, A1BD23, A1KB34, A2BT61, A2C6S8, A2T324, A3PEX4, A3PGI9, A4WVL6, A5DHT2, A5FIJ3, A5PJW8, A6GYU0, A6U851, A6YGE0, A8G6Y6, A8Z5T3, A9NAL4, B0R8D5, B0R8D6, B3E163, B3QC00, B5EFP3, B8YB55, C3MAX2, F4KD38, O27123, O27124, O28392, P06272, P08266, P08518, P09844, P09845, P0CX03, P0CX04, P11513, P22276, P23579

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
POLR3B	“form complex”	“RNA Polymerase III”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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	175.0×	3e-34
RNA Polymerase III Transcription Termination	16	137.0×	3e-31
RNA Polymerase III Transcription Initiation From Type 2 Promoter	18	131.3×	3e-34
RNA Polymerase III Transcription Initiation From Type 1 Promoter	18	126.6×	3e-34
RNA Polymerase III Transcription Initiation From Type 3 Promoter	18	126.6×	3e-34
RNA Polymerase III Transcription Initiation	18	104.2×	4e-32
RNA Polymerase III Transcription	18	101.3×	8e-32
RNA Polymerase III Abortive And Retractive Initiation	18	86.4×	3e-30

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase III	8	77.6×	3e-11
positive regulation of interferon-beta production	5	24.8×	3e-04
defense response to virus	9	7.9×	3e-04
transcription by RNA polymerase II	8	7.1×	2e-03
protein stabilization	8	6.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	28
Likely pathogenic	34
Uncertain significance	304
Likely benign	154
Benign	63

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1184080	NM_018082.6(POLR3B):c.312G>T (p.Leu104Phe)	Pathogenic
1184083	NM_018082.6(POLR3B):c.1018C>T (p.Arg340Ter)	Pathogenic
1190591	NM_018082.6(POLR3B):c.1373A>C (p.Gln458Pro)	Pathogenic
1300550	NM_018082.6(POLR3B):c.1285T>G (p.Phe429Val)	Pathogenic
1304259	NM_018082.6(POLR3B):c.1297C>T (p.Arg433Cys)	Pathogenic
1328976	NM_018082.6(POLR3B):c.1763del (p.Asp588fs)	Pathogenic
2096047	NM_018082.6(POLR3B):c.336del (p.Ile113fs)	Pathogenic
2426434	NC_000012.11:g.(?106848260)(106857418_?)del	Pathogenic
2571977	NM_018082.6(POLR3B):c.1765G>A (p.Gly589Arg)	Pathogenic
2626869	NM_018082.6(POLR3B):c.2511del (p.Ile838fs)	Pathogenic
2662581	NM_018082.6(POLR3B):c.833dup (p.Thr279fs)	Pathogenic
2778666	NM_018082.6(POLR3B):c.2904del (p.Lys968_Val969insTer)	Pathogenic
31162	NM_018082.6(POLR3B):c.1648C>T (p.Arg550Ter)	Pathogenic
31163	NM_018082.6(POLR3B):c.2778C>G (p.Asp926Glu)	Pathogenic
31164	NM_018082.6(POLR3B):c.1508C>A (p.Thr503Lys)	Pathogenic
31165	NM_018082.6(POLR3B):c.1533del (p.Ile511fs)	Pathogenic
31167	NM_018082.6(POLR3B):c.2686A>T (p.Lys896Ter)	Pathogenic
375867	NM_018082.6(POLR3B):c.2774C>A (p.Pro925Gln)	Pathogenic
419234	NM_018082.6(POLR3B):c.2777A>G (p.Asp926Gly)	Pathogenic
4534986	NM_018082.6(POLR3B):c.2571-1del	Pathogenic
4689839	NM_018082.6(POLR3B):c.1297C>G (p.Arg433Gly)	Pathogenic
4712798	NM_018082.6(POLR3B):c.3073dup (p.Arg1025fs)	Pathogenic
4739274	NM_018082.6(POLR3B):c.361C>T (p.Arg121Ter)	Pathogenic
4755696	NM_018082.6(POLR3B):c.637A>G (p.Arg213Gly)	Pathogenic
620581	NM_018082.6(POLR3B):c.2570+1G>A	Pathogenic
915417	NM_018082.6(POLR3B):c.2013dup (p.Ile672fs)	Pathogenic
972978	NM_018082.6(POLR3B):c.1094C>T (p.Ala365Val)	Pathogenic
987343	NM_018082.6(POLR3B):c.1112_1113del (p.Leu371fs)	Pathogenic
1048117	NM_018082.6(POLR3B):c.1277T>C (p.Leu426Ser)	Likely pathogenic
1048511	NM_018082.6(POLR3B):c.1385C>G (p.Thr462Arg)	Likely pathogenic

SpliceAI

4265 predictions. Top by Δscore:

Variant	Effect	Δscore
12:106357950:AGG:A	donor_loss	1.0000
12:106357951:GGT:G	donor_loss	1.0000
12:106366723:G:GG	donor_gain	1.0000
12:106369269:TTTCA:T	acceptor_loss	1.0000
12:106369272:CA:C	acceptor_loss	1.0000
12:106369273:A:AG	acceptor_gain	1.0000
12:106369273:A:AT	acceptor_loss	1.0000
12:106369274:G:GG	acceptor_gain	1.0000
12:106369274:GAT:G	acceptor_gain	1.0000
12:106369346:ATGAG:A	donor_loss	1.0000
12:106369347:TGAGG:T	donor_loss	1.0000
12:106369350:GGT:G	donor_loss	1.0000
12:106369351:G:A	donor_loss	1.0000
12:106369352:T:A	donor_loss	1.0000
12:106369581:A:AG	acceptor_gain	1.0000
12:106369582:G:GA	acceptor_gain	1.0000
12:106369582:GT:G	acceptor_gain	1.0000
12:106369582:GTGCC:G	acceptor_gain	1.0000
12:106369681:CAGGT:C	donor_loss	1.0000
12:106369682:AGG:A	donor_loss	1.0000
12:106369683:GGTG:G	donor_loss	1.0000
12:106369684:GTG:G	donor_loss	1.0000
12:106369685:T:A	donor_loss	1.0000
12:106378261:G:A	acceptor_gain	1.0000
12:106378380:ACCAG:A	donor_loss	1.0000
12:106378381:CCAGG:C	donor_loss	1.0000
12:106378382:CAGG:C	donor_loss	1.0000
12:106378383:AGG:A	donor_loss	1.0000
12:106378384:GG:G	donor_loss	1.0000
12:106378385:GTAT:G	donor_loss	1.0000

AlphaMissense

7475 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:106369292:T:A	V82D	1.000
12:106369583:T:C	C102R	1.000
12:106369585:C:G	C102W	1.000
12:106369586:C:A	R103S	1.000
12:106369611:C:A	A111D	1.000
12:106369623:T:A	V115E	1.000
12:106369679:G:C	G134R	1.000
12:106369680:G:A	G134D	1.000
12:106376387:T:C	C145R	1.000
12:106376389:T:G	C145W	1.000
12:106376435:T:C	C161R	1.000
12:106378287:G:A	G173R	1.000
12:106378287:G:C	G173R	1.000
12:106378288:G:A	G173E	1.000
12:106378288:G:T	G173V	1.000
12:106378294:A:T	E175V	1.000
12:106378378:T:A	V203D	1.000
12:106378383:A:C	S205R	1.000
12:106380031:C:A	S205R	1.000
12:106380031:C:G	S205R	1.000
12:106393109:A:C	S268R	1.000
12:106393111:T:A	S268R	1.000
12:106393111:T:G	S268R	1.000
12:106410922:G:C	D355H	1.000
12:106410923:A:C	D355A	1.000
12:106410923:A:G	D355G	1.000
12:106410923:A:T	D355V	1.000
12:106410932:G:A	G358D	1.000
12:106410937:A:G	K360E	1.000
12:106410939:G:C	K360N	1.000

dbSNP variants (sampled 300 via entrez): RS1000018192 (12:106469628 C>A,G), RS1000072509 (12:106484192 G>A), RS1000083013 (12:106505354 C>A), RS1000130727 (12:106408169 C>T), RS1000148281 (12:106432744 A>G), RS1000180456 (12:106477636 T>C), RS1000180685 (12:106371886 A>C,G), RS1000185623 (12:106430364 T>A), RS1000202689 (12:106494675 C>A), RS1000203806 (12:106418769 T>C), RS1000230131 (12:106379285 T>G), RS1000232936 (12:106371714 T>C), RS1000259149 (12:106425784 C>A), RS1000289254 (12:106432163 T>A), RS1000305195 (12:106478349 C>A,G,T)

Disease associations

OMIM: gene MIM:614366 | disease phenotypes: MIM:213002, MIM:614381, MIM:619742, MIM:607694, MIM:147950, MIM:146110, MIM:312080

GenCC curated gene-disease

Disease	Classification	Inheritance
hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism	Definitive	Autosomal recessive
Charcot-Marie-Tooth disease, demyelinating, IIA 1I	Strong	Autosomal dominant
neurodevelopmental disorder	Strong	Autosomal dominant
endosteal sclerosis-cerebellar hypoplasia syndrome	Supportive	Autosomal recessive
hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
POLR3B-related disorder	Definitive	AR
POLR3B-related disorder	Definitive	AD

Mondo (13): hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism (MONDO:0013722), Charcot-Marie-Tooth disease, demyelinating, IIA 1I (MONDO:0030677), POLR3B-related disorder (MONDO:0700277), POLR-related leukodystrophy (MONDO:0100605), leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism (MONDO:0011897), amenorrhea (MONDO:0001836), hypogonadotropic hypogonadism (MONDO:0018555), intellectual disability (MONDO:0001071), hypogonadotropic hypogonadism 7 with or without anosmia (MONDO:0007794), leukodystrophy (MONDO:0019046), (MONDO:0008940), (MONDO:0019505), neurodevelopmental disorder (MONDO:0700092)

Orphanet (10): Endosteal sclerosis-cerebellar hypoplasia syndrome (Orphanet:85186), Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome (Orphanet:88637), 4H leukodystrophy (Orphanet:289494), 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), Normosmic congenital hypogonadotropic hypogonadism (Orphanet:432), Leukodystrophy (Orphanet:68356), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

69 total (30 of 69 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000044	Hypogonadotropic hypogonadism
HP:0000252	Microcephaly
HP:0000511	Vertical supranuclear gaze palsy
HP:0000545	Myopia
HP:0000617	Abnormality of ocular smooth pursuit
HP:0000640	Gaze-evoked nystagmus
HP:0000648	Optic atrophy
HP:0000666	Horizontal nystagmus
HP:0000668	Hypodontia
HP:0000677	Oligodontia
HP:0000684	Delayed eruption of teeth
HP:0000695	Natal tooth
HP:0000750	Delayed speech and language development
HP:0000815	Hypergonadotropic hypogonadism
HP:0000823	Delayed puberty
HP:0001151	Impaired horizontal smooth pursuit
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001256	Mild intellectual disability
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001272	Cerebellar atrophy
HP:0001310	Dysmetria
HP:0001332	Dystonia
HP:0001337	Tremor

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000098_5	Cognitive test performance	3.000000e-06
GCST001635_2	Tourette syndrome	6.000000e-06
GCST002408_11	Response to methotrexate in juvenile idiopathic arthritis	4.000000e-06
GCST003220_1	Glioblastoma	3.000000e-09
GCST003228_3	Glioma	4.000000e-07
GCST003542_94	Night sleep phenotypes	5.000000e-06
GCST007565_18	Morning person	2.000000e-14
GCST007576_64	Chronotype	2.000000e-14
GCST010703_94	Brain morphology (MOSTest)	6.000000e-52

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0008328	chronotype measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D000568	Amenorrhea	C23.550.568.500
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C535353	Cerebellar hypoplasia with endosteal sclerosis (supp.)
C562785	Idiopathic Hypogonadotropic Hypogonadism (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, affects methylation	2
Formaldehyde	decreases expression	2
Valproic Acid	increases expression, affects expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, affects expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
abrine	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Cisplatin	affects expression	1
Ethyl Methanesulfonate	decreases expression	1
Lead	increases expression	1
Methyl Methanesulfonate	decreases expression	1
Oxygen	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Cyclosporine	decreases expression	1
Lithium Chloride	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A8NL	VUi025-A	Induced pluripotent stem cell	Female
CVCL_A8NM	VUi026-A	Induced pluripotent stem cell	Male
CVCL_A8NP	VUi028-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT01103518	PHASE4	UNKNOWN	Ethinyl Estradiol and Cyproterone Acetate in Irregular Menstruation
NCT01206153	PHASE4	COMPLETED	Metformin for Treatment Antipsychotic Induced Amenorrhea in Female Schizophrenic Patients
NCT02393482	PHASE4	UNKNOWN	Psychological Impact of Amenorrhea in Women With Endometriosis
NCT00328926	PHASE4	TERMINATED	Luveris® (Lutropin Alfa for Injection) in Women With Hypogonadotropic Hypogonadism (Luteinizing Hormone [LH] Less Than [<] 1.2 International Unit Per Liter [IU/L])
NCT01403532	PHASE4	COMPLETED	Sequential Therapy for Hypogonadotropic Hypogonadism
NCT01454011	PHASE4	COMPLETED	The Effect of Testosterone Replacement on the High Density Lipoprotein Cholesterol Subgroups
NCT01601327	PHASE4	COMPLETED	Effects of Medications in Patients With Hypogonadism
NCT02310074	PHASE4	UNKNOWN	Efficacy and Safety of Pulsatile Gonadotropin Releasing Hormone Pump Treatment in Patients With Idiopathic Hypogonadotropic Hypogonadism
NCT02880280	PHASE4	UNKNOWN	Human Menopausal Gonadotropin Combining With Human Chorionic Gonadotropin Treat Congenital Hypogonadotropic Hypogonadism
NCT03490513	PHASE4	COMPLETED	Aromatase Inhibitors and Weight Loss in Severely Obese Men With Hypogonadism
NCT04456296	PHASE4	COMPLETED	A Study of the Effect of Testosterone Replacement Therapy on Blood Pressure in Adult Male Participants With Hypogonadism
NCT05205837	PHASE4	TERMINATED	A Randomized, Double-blinded, Clinical, Placebo-controlled Trial on the Effects of Therapy With Letrozole and hUman Choriongonadotropin in Male Hypogonadism Induced by Illicit Use of Anabolic Androgenic Steroids- The LUCAS Trial
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
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00827151	PHASE3	WITHDRAWN	Bone Mass Accrual in Adolescent Athletes
NCT00467870	PHASE3	COMPLETED	Long-term Safety Study of Intramuscular Injections of 750 mg and 1000 mg Testosterone Undecanoate in Hypogonadal Men
NCT00962637	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Androxal™ Treatment in Men With Secondary Hypogonadism
NCT01067365	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Androxal Treatment in Men With Secondary Hypogonadism
NCT01532414	PHASE3	COMPLETED	Phase III Study to Evaluated Morning Testosterone Normalization in Men With Secondary Hypogonadism
NCT01534208	PHASE3	COMPLETED	Safety Study of Enclomiphene Citrate in the Treatment of Men With Secondary Hypogonadism
NCT01709331	PHASE3	COMPLETED	A Study of the Efficacy and Safety of Corifollitropin Alfa (MK-8962) in Combination With Human Chorionic Gonadotropin (hCG) in Adult Men With Hypogonadotropic Hypogonadism (HH) (P07937)
NCT01739582	PHASE3	COMPLETED	An Extension Study of Enclomiphene Citrate in the Treatment of Men With Secondary Hypogonadism
NCT01739595	PHASE3	COMPLETED	Phase III Study to Evaluate Morning Testosterone Normalization in Overweight Men With Secondary Hypogonadism
NCT01993212	PHASE3	COMPLETED	A Randomized, Double Blind, Placebo-Controlled, Multi-Center Phase III Study in Men With Acquired Hypogonadotropic Hypogonadism to Compare Changes in Testosterone and Sperm Concentration Following Treatment With 12.5 mg or 25 mg Androxal or AndroGel 1.62%
NCT01993225	PHASE3	COMPLETED	A Randomized, Double Blind, Placebo-Controlled, Multi-Center Phase III Study in Men With Acquired Hypogonadotropic Hypogonadism to Compare Changes in Testosterone and Sperm Concentration Following Treatment With 12.5 mg or 25 mg Androxal or AndroGel 1.62%
NCT02110368	PHASE3	COMPLETED	Bioequivalence Study of Test and Reference Testosterone Topical Gel, 1.62% Metered Pump in Testosterone Deficient Adult Male Subjects Under Fasting Conditions
NCT03019575	PHASE3	COMPLETED	Efficacy and Safety of Corifollitropin Alfa (MK-8962) in Combination With Human Chorionic Gonadotropin (hCG) in Adolescent Males With Hypogonadotropic Hypogonadism (HH) (MK-8962-043)
NCT06561594	PHASE3	NOT_YET_RECRUITING	To Evaluate Recombinant Human Follicle Stimulating Hormone-CTP Fusion Protein Injection or Placebo Combined With Chorionic Gonadotropin for Injection
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
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism