RNA POLYMERASE III TRANSCRIPTION PATHWAY (PW:0000128)
Description
The three eukaryotic RNA polymerases (RNAPs)- Pol I, II and III, transcribe different sets of genes and require distinct sets of factors to assemble a specific initiation complex which recruits them on gene promoters. The multi-subunit enzymes are composed of 14 (RNAPI), 12 (RNAPII) and 17 (RNAPIII) subunits of which some are shared and others are unique, yet converging on an overall similar structural topology. Complexes specific to each of the three systems share the universal transcription factor 'TATA-box binding protein' (TBP) regardless of whether the promoters have a TATA box or not. In addition, modules and domains present in general transcription factors (GTFs) specific for RNAPII are found in subunits of RNAPI and RNAPIII and/or RNAPI and RNAPIII specific factors. The initiation, elongation and termination of transcription are steps shared by all systems, albeit with differing details and/or degrees of complexity. Beyond the shared or related elements, specific factors confer unique topological and functional features to the particular initiation complex associated with the three polymerases and account for the differences in promoter recognition and the class or category of transcribed genes. Pol I transcribes ribosomal RNA, all protein-coding and many non-coding genes are transcribed by pol II, while transfer RNA (tRNA), the small 5S ribosomal RNA (5SrRNA) and a subset of small non-coding genes are the realm of pol III mediated transcription. Transcription by RNA pol III is described here.
RNA polymerase III transcription pathway
Pol III is responsible for the transcription of all tRNA, the small ribosomal 5SrRNA and several other non-coding RNAs including U6 spliceosomal RNA, vault and Y RNAs. Largely, pol III promoters are characterized by the presence of internal elements downstream of the transcription start site (TSS). This is the case for type I and type II promoters involved in the transcription of 5S ribosomal RNA (5SrRNA) and of transfer RNA (tRNA) genes, respectively. Type I promoters exhibit an internal/intermediate element (IE) and the C box, recognized by the transcription factor IIIA (TFIIIA) which then recruits the multi-subunit transcription factor IIIC (TFIIIC). Type II promoters have the two, highly conserved A and B boxes, directly recognized by TFIIIC. TFIIIC is responsible for recruiting the core pol III transcription factor IIIB (TFIIIB) upstream of the transcription start site (TSS), which then recruits the polymerase. A type III promoter is only present in vertebrates, has a canonical TATA box and an upstream proximal sequence element (PSE), recognized by the multi-subunit SNAPc binding factor (small nuclear RNA activating protein complex), also known as PBP or PTF. Upstream factors, such as Pou2f1 (Oct-1) or Zfp143 (Staf), bound to distal promoter element (DSE), reinforce the interaction of SNAPc with PSE. Cooperative binding of SNAPc and TFIIIB to PSE and TATA box, respectively, results in Pol III recruitment. TFIIIA, which binds both the 5S rRNA gene promoter and 5S RNA itself, has nine archetypal zinc-finger motifs underlying the DNA and RNA recognition versatility and specificity. TFIIIC consists of six subunits GTF3C1-to-C6, in turn part of two sub-complexes ¿ tA and tB binding to the A and B box, respectively. By comparison with yeast, where many pol II studies have been carried out, the human tB sub-complex consists of GTF3C1, 2 and 4 and the tA sub-complex, of GTF3C3, 5 and 6. Despite the central role of TFIIIC in transcription from type I and II promoters, the molecular mechanisms of both transcription and the reported extra-transcriptional activity, remain to be elucidated. The upstream SNAPc is composed of five subunits SNAPC1-to-C5. The core TFIIIB is composed of TBP, Bdp1 and either Brf1 in type I and II promoters, or Brf2 in type III promoters. The N-terminus of Brf1 and 2 has homology to TFIIB, the core pol II transcription factor while the C-terminus interacts with TBP, pol III and Bdp1. Despite a low sequence homology, both the yeast and human Bdp1 proteins possess a SANT domain responsible for the interaction with Brf1/2. The three forms of human BDP1, arising from alternative splicing, all preserve the SANT domain. Once recruited, pol III and GTFs are part of a preinitiation complex (PIC) which transitions from a closed to the transcription-prone conformation.
Pol III, with 17 subunits, is the largest of the three eukaryotic polymerases. Of these, five are shared with pol I and II and additional two, with pol I. The remaining are pol III specific; the two largest form the active center and nucleic acid binding cleft, other two form the stalk structure, one subunit performs RNA cleavage during backtracking and the remaining five form one heterodimer and one heterotrimer. The heterodimer is distantly related to pol II TFIIF and plays a role in all stages of pol III transcription, the heterotrimer is distantly related to pol II TFIIE and plays a role in transcription initiation. Subunits within the trimer contain winged-helix (WH) domains and this, along with coordinated contributions from heterodimer domains and TFIIIB, underlie the opening of PIC and melting of DNA, which in contrast to pol II, does not require energy. Once transcription is initiated, the elongation step does not require additional factors. Conformational changes in pol III subsequent to binding the transcription bubble, particularly in the specific sub-complexes, are thought to increase the processivity of the enzyme. The presence of several thymidine (T) residues on the non-template (coding) strand, represents the termination signal, an event in which the heterodimeric pol III sub-complex plays an important role. Reinitiation of transcription (several rounds of transcription on the same gene), also referred to as facilitated recycling, is a distinguishing feature of pol III system with TFIIIB playing an important role. The chromatin associated protein Sub1, with multiple roles in gene expression, acts as a reinitiation factor - it interacts with components of TFIIIB and TFIIIC upon which it exerts a stabilizing effect and is able to bend DNA. Pol III subunits are involved in termination and the coupling of termination and reinitiation. Other factors may also contribute to reinitiation, but their role awaits further investigation. Several repression systems regulate pol III transcription system of which Maf1 is an essential regulator whose interaction with pol III and the Brf1 component of TFIIIIB preclude de novo assembly of transcription complex. Under normal conditions, Maf1 is phosphorylated and resides in the cytoplasm; stresses lead to its dephosphorylation and import into the nucleus where it represses pol III. Human MAF1 may be a substrate of mTorc1 kinase complex of mTOR signaling pathway. The retinoblastoma tumor suppressor Rb1 globally inhibits pol III transcription via association with TFIIIB-Brf1 for type II promoter loci and with components of SNAPc for type III loci. Maturation of tRNA includes removal of 5' leader, of 3' trailer and addition of CCA, splicing of intron containing genes and the myriad modifications whose function is still to be elucidated. Unlike the maturation of other RNA transcripts, which largely occurs cotranscriptionally, tRNA processing, as seen in the yeast system, takes place in many compartments. To see the ontology report for annotations, GViewer and download, click here
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Pathway Diagram:
Genes in Pathway:
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Bdp1
B double prime 1, subunit of RNA polymerase III transcription initiation factor IIIB
ISO
RGD
PMID:20890107 PMID:23031840
RGD:9685218 , RGD:9588284
NCBI chr 2:31,378,407...31,470,140
Ensembl chr 2:31,378,924...31,470,119
G
Brf1
BRF1, RNA polymerase III transcription initiation factor subunit
ISO
RGD
PMID:20890107 PMID:23031840
RGD:9685218 , RGD:9588284
NCBI chr 6:132,034,378...132,081,313
Ensembl chr 6:132,037,272...132,081,278
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Brf2
BRF2, RNA polymerase III transcription initiation factor subunit
ISO
RGD
PMID:20890107 PMID:23031840
RGD:9685218 , RGD:9588284
NCBI chr16:64,928,334...64,933,057
Ensembl chr16:64,928,300...64,933,059
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Crcp
CGRP receptor component
ISO
RGD
PMID:12391170
RGD:9685217
NCBI chr12:26,623,968...26,659,756
Ensembl chr12:26,623,976...26,768,225
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Gtf3a
general transcription factor III A
ISO
RGD
PMID:23031840
RGD:9588284
NCBI chr12:8,136,746...8,144,690
Ensembl chr12:8,136,747...8,144,690
G
Gtf3c1
general transcription factor IIIC subunit 1
ISO
RGD
PMID:23031840
RGD:9588284
NCBI chr 1:180,203,995...180,270,201
Ensembl chr 1:180,203,995...180,270,201
G
Gtf3c2
general transcription factor IIIC subunit 2
ISO
RGD
PMID:23031840
RGD:9588284
NCBI chr 6:25,196,439...25,221,338
Ensembl chr 6:25,197,268...25,220,490
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Gtf3c3
general transcription factor IIIC subunit 3
ISO
RGD
PMID:23031840
RGD:9588284
NCBI chr 9:55,882,252...55,943,037
Ensembl chr 9:55,883,721...55,942,967
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Gtf3c4
general transcription factor IIIC subunit 4
ISO
RGD
PMID:23031840
RGD:9588284
NCBI chr 3:12,154,803...12,172,795
Ensembl chr 3:12,154,805...12,172,725
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Gtf3c5
general transcription factor IIIC subunit 5
ISO
RGD
PMID:23031840
RGD:9588284
NCBI chr 3:11,893,867...11,914,187
Ensembl chr 3:11,893,875...11,914,180
G
Gtf3c6
general transcription factor 3C subunit 6
ISO
RGD
PMID:23031840
RGD:9588284
NCBI chr20:43,656,400...43,668,382
Ensembl chr20:43,655,875...43,667,873
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Maf1
MAF1 homolog, negative regulator of RNA polymerase III
ISO
RGD
PMID:23031840 PMID:23165150
RGD:9588284 , RGD:9685221
NCBI chr 7:108,075,173...108,078,252
Ensembl chr 7:108,075,189...108,078,249
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Polr1c
RNA polymerase I and III subunit C
ISO
RGD
PMID:12391170 PMID:20890107
RGD:9685217 , RGD:9685218
NCBI chr 9:14,735,740...14,739,852
Ensembl chr 9:14,735,714...14,739,852
G
Polr1d
RNA polymerase I and III subunit D
ISO
RGD
PMID:12391170 PMID:20890107
RGD:9685217 RGD:9685218
NCBI chr12:7,970,592...8,004,157
Ensembl chr12:7,970,595...8,005,624
G
Polr2e
RNA polymerase II, I and III subunit E
ISO
RGD
PMID:12391170 PMID:20890107
RGD:9685217 , RGD:9685218
NCBI chr 7:9,666,695...9,670,638
Ensembl chr 7:9,666,716...9,670,643
G
Polr2f
RNA polymerase II, I and III subunit F
ISO
RGD
PMID:12391170 PMID:20890107
RGD:9685217 , RGD:9685218
NCBI chr 7:110,712,528...110,724,234
Ensembl chr 7:110,712,572...110,724,234
G
Polr2h
RNA polymerase II, I and III subunit H
ISO
RGD
PMID:12391170 PMID:20890107
RGD:9685217 RGD:9685218
NCBI chr11:80,192,017...80,197,468
Ensembl chr11:80,192,032...80,197,515 Ensembl chr10:80,192,032...80,197,515
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Polr2k
RNA polymerase II, I and III subunit K
ISO
RGD
PMID:12391170 PMID:20890107
RGD:9685217 , RGD:9685218
NCBI chr 7:67,347,118...67,359,466
Ensembl chr 7:67,356,113...67,357,668
G
Polr2l
RNA polymerase II, I and III subunit L
ISO
RGD
PMID:12391170 PMID:20890107
RGD:9685217 RGD:9685218
NCBI chr 1:196,570,051...196,572,060
G
Polr3a
RNA polymerase III subunit A
ISO
RGD
PMID:12391170 PMID:20890107
RGD:9685217 , RGD:9685218
NCBI chr16:49,178...88,178
Ensembl chr16:49,521...88,172
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Polr3b
RNA polymerase III subunit B
ISO
RGD
PMID:12391170 PMID:20890107
RGD:9685217 , RGD:9685218
NCBI chr 7:19,039,179...19,142,450
Ensembl chr 7:19,038,552...19,142,598
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Polr3c
RNA polymerase III subunit C
ISO
RGD
PMID:12391170 PMID:20890107
RGD:9685217 , RGD:9685218
NCBI chr 2:184,246,201...184,262,150
Ensembl chr 2:184,246,204...184,262,208
G
Polr3d
RNA polymerase III subunit D
ISO
RGD
PMID:12391170 PMID:20890107
RGD:9685217 , RGD:9685218
NCBI chr15:45,511,587...45,516,256
Ensembl chr15:45,511,589...45,516,353
G
Polr3e
RNA polymerase III subunit E
ISO
RGD
PMID:12391170 PMID:20890107
RGD:9685217 , RGD:9685218
NCBI chr 1:175,466,091...175,494,679
Ensembl chr 1:175,466,127...175,494,667
G
Polr3f
RNA polymerase III subunit F
ISO
RGD
PMID:12391170 PMID:20890107
RGD:9685217 , RGD:9685218
NCBI chr 3:131,908,466...131,924,838
Ensembl chr 3:131,908,466...131,924,837
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Polr3g
RNA polymerase III subunit G
ISO
RGD
PMID:12391170 PMID:20890107
RGD:9685217 , RGD:9685218
NCBI chr 2:11,945,215...11,986,125
Ensembl chr 2:11,945,217...11,986,125
G
Polr3gl
RNA polymerase III subunit GL
ISO
RGD
PMID:20890107
RGD:9685218
NCBI chr 2:184,111,570...184,129,200
Ensembl chr 2:184,112,510...184,129,114
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Polr3h
RNA polymerase III subunit H
ISO
RGD
PMID:12391170 PMID:20890107
RGD:9685217 , RGD:9685218
NCBI chr 7:113,429,434...113,439,743
Ensembl chr 7:113,429,451...113,439,778
G
Polr3k
RNA polymerase III subunit K
ISO
RGD
PMID:12391170 PMID:20890107
RGD:9685217 , RGD:9685218
NCBI chr 3:168,982,846...168,987,043
Ensembl chr 3:168,982,812...168,987,040
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Pou2f1
POU class 2 homeobox 1
ISO
RGD
PMID:20890107
RGD:9685218
NCBI chr13:78,120,617...78,263,306
Ensembl chr13:78,130,685...78,263,363
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Rb1
RB transcriptional corepressor 1
ISO
RGD
PMID:23063750
RGD:9685222
NCBI chr15:48,371,295...48,502,473
Ensembl chr15:48,371,296...48,502,302
G
Snapc1
small nuclear RNA activating complex, polypeptide 1
ISO
RGD
PMID:23031840
RGD:9588284
NCBI chr 6:92,684,785...92,710,772
Ensembl chr 6:92,684,752...92,707,746
G
Snapc2
small nuclear RNA activating complex, polypeptide 2
ISO
RGD
PMID:23031840
RGD:9588284
NCBI chr12:2,605,794...2,608,997
Ensembl chr12:2,605,810...2,608,999
G
Snapc3
small nuclear RNA activating complex, polypeptide 3
ISO
RGD
PMID:23031840
RGD:9588284
NCBI chr 5:97,817,827...97,868,494
Ensembl chr 5:97,817,947...97,844,650
G
Snapc4
small nuclear RNA activating complex, polypeptide 4
ISO
RGD
PMID:23031840
RGD:9588284
NCBI chr 3:9,182,061...9,200,819
Ensembl chr 3:9,182,067...9,199,518
G
Snapc5
small nuclear RNA activating complex, polypeptide 5
ISO
RGD
PMID:23031840
RGD:9588284
NCBI chr 8:64,677,204...64,680,769
Ensembl chr 8:64,677,205...64,681,964
G
Sub1
SUB1 regulator of transcription
ISO
RGD
PMID:23165150 PMID:23128323
RGD:9685221 , RGD:9685220
NCBI chr 2:61,005,646...61,020,486
Ensembl chr 2:61,005,666...61,020,436 Ensembl chr 2:61,005,666...61,020,436
G
Tbp
TATA box binding protein
ISO
RGD
PMID:20890107 PMID:23031840
RGD:9685218 , RGD:9588284
NCBI chr 1:56,463,330...56,480,430
Ensembl chr 1:56,463,618...56,510,016
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Zfp143
zinc finger protein 143
ISO
RGD
PMID:20890107
RGD:9685218
NCBI chr 1:164,109,041...164,144,902
Ensembl chr 1:164,109,116...164,144,902
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Clp1
cleavage factor polyribonucleotide kinase subunit 1
ISO
RGD
PMID:25071838
RGD:9685342
NCBI chr 3:69,806,774...69,818,633
Ensembl chr 3:69,806,778...69,810,421
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Elac1
elaC ribonuclease Z 1
ISO
RGD
PMID:21572561
RGD:9685334
NCBI chr18:67,321,231...67,341,358
Ensembl chr18:67,323,583...67,340,936
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Elac2
elaC ribonuclease Z 2
ISO
RGD
PMID:21572561
RGD:9685334
NCBI chr10:49,632,308...49,655,614
Ensembl chr10:49,632,378...49,655,614
G
Pop1
POP1 homolog, ribonuclease P/MRP subunit
ISO
RGD
PMID:19931535 PMID:19931535
RGD:9685326 , RGD:9685326
NCBI chr 7:65,705,348...65,733,143
Ensembl chr 7:65,705,368...65,733,141
G
Pop4
POP4 homolog, ribonuclease P/MRP subunit
ISO
RGD
PMID:19931535
RGD:9685326
NCBI chr 1:90,960,026...90,968,360
Ensembl chr 1:90,960,022...90,968,443
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Pop5
POP5 homolog, ribonuclease P/MRP subunit
ISO
RGD
PMID:19931535
RGD:9685326
NCBI chr12:41,376,755...41,384,882
Ensembl chr12:41,376,755...41,381,336
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Pop7
POP7 homolog, ribonuclease P/MRP subunit
ISO
RGD
PMID:19931535
RGD:9685326
NCBI chr12:19,189,384...19,190,425
Ensembl chr12:19,189,138...19,190,674
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Rpp14
ribonuclease P/MRP subunit p14
ISO
RGD
PMID:19931535
RGD:9685326
NCBI chr15:16,837,796...16,847,970
Ensembl chr15:16,836,859...16,852,101 Ensembl chr15:16,836,859...16,852,101
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Rpp21
ribonuclease P/MRP subunit p21
ISO
RGD
PMID:19931535
RGD:9685326
NCBI chr20:2,018,170...2,020,100
Ensembl chr20:2,018,147...2,020,106
G
Rpp25
ribonuclease P and MRP subunit p25
ISO
RGD
PMID:19931535
RGD:9685326
NCBI chr 8:57,907,352...57,908,732
Ensembl chr 8:57,907,352...57,908,732
G
Rpp30
ribonuclease P/MRP subunit p30
ISO
RGD
PMID:19931535
RGD:9685326
NCBI chr 1:233,786,048...233,808,958
Ensembl chr 1:233,786,099...233,808,952
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Rpp38
ribonuclease P/MRP subunit p38
ISO
RGD
PMID:19931535
RGD:9685326
NCBI chr17:74,914,066...74,917,742
Ensembl chr17:74,908,932...74,927,431
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Rpp40
ribonuclease P/MRP subunit p40
ISO
RGD
PMID:19931535
RGD:9685326
NCBI chr17:28,947,752...28,956,788
Ensembl chr17:28,947,734...28,956,788
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Rtcb
RNA 2',3'-cyclic phosphate and 5'-OH ligase
ISO
RGD
PMID:25071838
RGD:9685342
NCBI chr 7:17,907,668...17,927,136
Ensembl chr 7:17,907,705...17,927,132
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Ssb
small RNA binding exonuclease protection factor La
ISO
RGD
PMID:21572561
RGD:9685334
NCBI chr 3:54,616,616...54,626,203
Ensembl chr 3:54,616,619...54,626,203
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Tsen15
tRNA splicing endonuclease subunit 15
ISO
RGD
PMID:25071838
RGD:9685342
NCBI chr13:64,490,216...64,505,591
Ensembl chr13:64,490,218...64,505,617
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Tsen2
tRNA splicing endonuclease subunit 2
ISO
RGD
PMID:25071838
RGD:9685342
NCBI chr 4:148,602,805...148,638,219
Ensembl chr 4:148,602,863...148,638,215
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Tsen34
tRNA splicing endonuclease subunit 34
ISO
RGD
PMID:25071838
RGD:9685342
NCBI chr 1:65,517,324...65,525,194
Ensembl chr 1:65,517,330...65,524,412
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Tsen54
tRNA splicing endonuclease subunit 54
ISO
RGD
PMID:25071838
RGD:9685342
NCBI chr10:101,041,607...101,050,088
Ensembl chr10:101,042,503...101,050,087
Pathway Gene Annotations
Disease Annotations Associated with Genes in the RNA polymerase III transcription pathway
Bdp1 3-Methylcrotonyl-CoA carboxylase 2 deficiency , autosomal recessive nonsyndromic deafness 112 , Deafness , Hearing Loss , Neurodevelopmental Disorders Brf1 Breast Neoplasms , Cardiomegaly , cerebellofaciodental syndrome , Charcot-Marie-Tooth disease axonal type 2O , colorectal cancer , developmental and epileptic encephalopathy 66 , fibroma , focal segmental glomerulosclerosis 5 , genetic disease , intellectual disability , sensorineural hearing loss Brf2 hereditary spastic paraplegia 54 , hypogonadotropic hypogonadism 2 with or without anosmia , paraplegia , prostate cancer Crcp argininosuccinic aciduria , Hyperalgesia , pleomorphic xanthoastrocytoma , sciatic neuropathy Gtf3a human immunodeficiency virus infectious disease Gtf3c1 neuronal ceroid lipofuscinosis , Tracheoesophageal Fistula Gtf3c2 Tatton-Brown-Rahman syndrome Gtf3c3 Neurodevelopmental Disorders Gtf3c4 developmental and epileptic encephalopathy 14 , Ehlers-Danlos syndrome classic type 1 , Leigh disease , primary coenzyme Q10 deficiency 7 , Rafiq syndrome , tuberous sclerosis 1 Gtf3c5 developmental and epileptic encephalopathy 14 , Ehlers-Danlos syndrome classic type 1 , Leigh disease , primary coenzyme Q10 deficiency 7 , Rafiq syndrome , tuberous sclerosis 1 Maf1 Brown-Vialetto-Van Laere syndrome 2 , epidermolysis bullosa simplex with muscular dystrophy , holoprosencephaly Polr1c atherosclerosis , breast cancer , CAKUT , Carey-Fineman-Ziter Syndrome 2 , cholangiocarcinoma , combined oxidative phosphorylation deficiency , combined oxidative phosphorylation deficiency 8 , developmental and epileptic encephalopathy , diabetic angiopathy , genetic disease , head and neck squamous cell carcinoma , Hearing Loss , hemolytic disease of the fetus , hypomyelinating leukodystrophy 11 , hypomyelinating leukodystrophy 26 , infantile Refsum disease , intellectual disability , JABERI-ELAHI SYNDROME , Lung Agenesis , Mandibulofacial Dysostosis , neurodegeneration with brain iron accumulation , primary ciliary dyskinesia , primary ciliary dyskinesia 12 , progressive leukoencephalopathy with ovarian failure , spondyloepimetaphyseal dysplasia with joint laxity , Treacher Collins syndrome 3 , xeroderma pigmentosum , xeroderma pigmentosum variant type , Zellweger syndrome Polr1d Animal Disease Models , genetic disease , Hearing Loss , lung adenocarcinoma , Mandibulofacial Dysostosis , substance-related disorder , Treacher Collins syndrome , Treacher Collins syndrome 2 Polr2e cerebral creatine deficiency syndrome , cyclic hematopoiesis , Dwarfism , Peutz-Jeghers syndrome Polr2f adenylosuccinase lyase deficiency , Anosmia , Charcot-Marie-Tooth disease , Deafness , Emery-Dreifuss muscular dystrophy , genetic disease , Hearing Loss , Hirschsprung Disease 1 , Hirschsprung's disease , intellectual disability , Kallmann syndrome , myoclonic dystonia 26 , neurodegeneration with brain iron accumulation 2A , Olfaction Disorders , PCWH syndrome , Van der Hoeve Halbertsma Waardenburg Gualdi Syndrome , Waardenburg syndrome , Waardenburg syndrome type 1 , Waardenburg syndrome type 2A , Waardenburg syndrome type 2E , Waardenburg syndrome type 4A , Waardenburg syndrome type 4C Polr2h 3-Methylcrotonyl-CoA carboxylase 1 deficiency , congenital disorder of glycosylation Id , Currarino syndrome Polr2k Cohen syndrome , Kartagener syndrome , primary ciliary dyskinesia 28 Polr2l delta beta-thalassemia , developmental and epileptic encephalopathy , early infantile epileptic encephalopathy , immunodeficiency 39 , neuronal ceroid lipofuscinosis , Segawa Syndrome, Autosomal Recessive Polr3a Diamond-Blackfan anemia , Diamond-Blackfan anemia 3 , Dysmyelinating Leukodystrophy with Oligodontia , genetic disease , Genitopatellar Syndrome , hypomyelinating leukodystrophy , hypomyelinating leukodystrophy 4 , hypomyelinating leukodystrophy 7 , hypomyelinating leukodystrophy 8 , leukodystrophy , metachromatic leukodystrophy , spastic ataxia , Wiedemann-Rautenstrauch syndrome Polr3b amenorrhea , Charcot-Marie-Tooth Disease Type 1I , Dysmyelinating Leukodystrophy with Oligodontia , genetic disease , hypogonadism , hypogonadotropic hypogonadism , hypogonadotropic hypogonadism 7 with or without anosmia , hypomyelinating leukodystrophy 7 , hypomyelinating leukodystrophy 8 , intellectual disability , Klinefelter syndrome Polr3c gastrointestinal stromal tumor , neutropenia , parathyroid carcinoma , schizophrenia , thrombocytopenia-absent radius syndrome Polr3d Conotruncal Cardiac Defects Polr3e autistic disorder , chromosome 16p12.1 deletion syndrome , schizophrenia Polr3f congenital dyserythropoietic anemia type II , familial hyperinsulinemic hypoglycemia 1 , IMMUNODEFICIENCY 101 (VARICELLA ZOSTER VIRUS-SPECIFIC) Polr3g autistic disorder , familial adenomatous polyposis 1 , Hereditary Neoplastic Syndromes , Neurodevelopmental Disorders Polr3gl Dwarfism , gastrointestinal stromal tumor , hemochromatosis type 2A , parathyroid carcinoma , schizophrenia , SHORT STATURE, OLIGODONTIA, DYSMORPHIC FACIES, AND MOTOR DELAY , thrombocytopenia-absent radius syndrome Polr3h adenylosuccinase lyase deficiency , common variable immunodeficiency 4 , genetic disease , infantile cerebellar-retinal degeneration , optic atrophy 9 , primary ovarian insufficiency Polr3k Disease Progression , hypomyelinating leukodystrophy 21 , Stomach Neoplasms Pou2f1 gastrointestinal stromal tumor , parathyroid carcinoma Rb1 Acute Erythroleukemia , acute kidney failure , acute lymphoblastic leukemia , Adrenal Gland Neoplasms , adrenocortical carcinoma , Animal Mammary Neoplasms , Autosomal Recessive Woolly Hair , B-lymphoblastic leukemia/lymphoma , B-lymphoblastic leukemia/lymphoma with ETV6-RUNX1 , basal cell carcinoma , bone osteosarcoma , brain ischemia , Breast Neoplasms , carcinoma , Cardiomegaly , cervix uteri carcinoma in situ , chromosome 13q14 deletion syndrome , disease of cellular proliferation , ductal carcinoma in situ , embryonal carcinoma , Endometrial Neoplasms , esophagus squamous cell carcinoma , Experimental Liver Neoplasms , Experimental Mammary Neoplasms , Experimental Neoplasms , familial retinoblastoma , gastrointestinal stromal tumor , genetic disease , glioblastoma , glioblastoma proneural subtype , head and neck squamous cell carcinoma , hepatocellular carcinoma , Hereditary Neoplastic Syndromes , hereditary nonpolyposis colorectal cancer type 4 , hypotrichosis 8 , in situ carcinoma , Insulin Resistance , intellectual disability , intestinal pseudo-obstruction , lung adenocarcinoma , lung non-small cell carcinoma , lung oat cell carcinoma , lung small cell carcinoma , medulloblastoma , mitochondrial DNA depletion syndrome 5 , Neoplasm Metastasis , obesity , oligodendroglioma , osteosarcoma , ovarian cancer , Ovarian Neoplasms , pancreatic cancer , Phyllodes Tumor , Pituitary Neoplasms , prostate cancer , Prostatic Neoplasms , renal cell carcinoma , retinoblastoma , seminoma , Sezary's disease , small cell carcinoma , squamous cell carcinoma , Stevens-Johnson syndrome , trilateral retinoblastoma , urinary bladder cancer , Urinary Bladder Neoplasm Snapc2 familial hemophagocytic lymphohistiocytosis 5 , mucolipidosis type IV Snapc4 Adams-Oliver Syndrome 5 , autosomal dominant intellectual developmental disorder 8 , autosomal dominant nocturnal frontal lobe epilepsy 5 , developmental and epileptic encephalopathy 14 , Ehlers-Danlos syndrome classic type 1 , genetic disease , Immunodeficiency 103 , Joubert syndrome 1 , Kleefstra syndrome 1 , Leigh disease , long QT syndrome , NEURODEVELOPMENTAL DISORDER WITH MOTOR REGRESSION, PROGRESSIVE SPASTIC PARAPLEGIA, AND OROMOTOR DYSFUNCTION , primary coenzyme Q10 deficiency 7 , Rafiq syndrome , tuberous sclerosis 1 Snapc5 Bloom syndrome , cardiofaciocutaneous syndrome , colorectal cancer , long QT syndrome , melanoma , neuronal ceroid lipofuscinosis , Noonan syndrome , RASopathy Sub1 Neurodevelopmental Disorders Tbp Alzheimer's disease , amenorrhea , genetic disease , Huntington's disease , late onset Parkinson's disease , schizophrenia , sleep apnea , Spinal Cord Injuries , spinocerebellar ataxia type 17 , Spinocerebellar Ataxias , type 1 diabetes mellitus
3-Methylcrotonyl-CoA carboxylase 1 deficiency Polr2h 3-Methylcrotonyl-CoA carboxylase 2 deficiency Bdp1 Acute Erythroleukemia Rb1 acute kidney failure Rb1 acute lymphoblastic leukemia Rb1 Adams-Oliver Syndrome 5 Snapc4 adenylosuccinase lyase deficiency Polr2f , Polr3h Adrenal Gland Neoplasms Rb1 adrenocortical carcinoma Rb1 Alzheimer's disease Tbp amenorrhea Polr3b , Tbp Animal Disease Models Polr1d Animal Mammary Neoplasms Rb1 Anosmia Polr2f argininosuccinic aciduria Crcp atherosclerosis Polr1c autistic disorder Polr3e , Polr3g autosomal dominant intellectual developmental disorder 8 Snapc4 autosomal dominant nocturnal frontal lobe epilepsy 5 Snapc4 autosomal recessive nonsyndromic deafness 112 Bdp1 Autosomal Recessive Woolly Hair Rb1 B-lymphoblastic leukemia/lymphoma Rb1 B-lymphoblastic leukemia/lymphoma with ETV6-RUNX1 Rb1 basal cell carcinoma Rb1 Bloom syndrome Snapc5 bone osteosarcoma Rb1 brain ischemia Rb1 breast cancer Polr1c Breast Neoplasms Brf1 , Rb1 Brown-Vialetto-Van Laere syndrome 2 Maf1 CAKUT Polr1c carcinoma Rb1 cardiofaciocutaneous syndrome Snapc5 Cardiomegaly Brf1 , Rb1 Carey-Fineman-Ziter Syndrome 2 Polr1c cerebellofaciodental syndrome Brf1 cerebral creatine deficiency syndrome Polr2e cervix uteri carcinoma in situ Rb1 Charcot-Marie-Tooth disease Polr2f Charcot-Marie-Tooth disease axonal type 2O Brf1 Charcot-Marie-Tooth Disease Type 1I Polr3b cholangiocarcinoma Polr1c chromosome 13q14 deletion syndrome Rb1 chromosome 16p12.1 deletion syndrome Polr3e Cohen syndrome Polr2k colorectal cancer Brf1 , Snapc5 combined oxidative phosphorylation deficiency Polr1c combined oxidative phosphorylation deficiency 8 Polr1c common variable immunodeficiency 4 Polr3h congenital disorder of glycosylation Id Polr2h congenital dyserythropoietic anemia type II Polr3f Conotruncal Cardiac Defects Polr3d Currarino syndrome Polr2h cyclic hematopoiesis Polr2e Deafness Bdp1 , Polr2f delta beta-thalassemia Polr2l developmental and epileptic encephalopathy Polr1c , Polr2l developmental and epileptic encephalopathy 14 Gtf3c4 , Gtf3c5 , Snapc4 developmental and epileptic encephalopathy 66 Brf1 diabetic angiopathy Polr1c Diamond-Blackfan anemia Polr3a Diamond-Blackfan anemia 3 Polr3a disease of cellular proliferation Rb1 Disease Progression Polr3k ductal carcinoma in situ Rb1 Dwarfism Polr2e , Polr3gl Dysmyelinating Leukodystrophy with Oligodontia Polr3a , Polr3b early infantile epileptic encephalopathy Polr2l Ehlers-Danlos syndrome classic type 1 Gtf3c4 , Gtf3c5 , Snapc4 embryonal carcinoma Rb1 Emery-Dreifuss muscular dystrophy Polr2f Endometrial Neoplasms Rb1 epidermolysis bullosa simplex with muscular dystrophy Maf1 esophagus squamous cell carcinoma Rb1 Experimental Liver Neoplasms Rb1 Experimental Mammary Neoplasms Rb1 Experimental Neoplasms Rb1 familial adenomatous polyposis 1 Polr3g familial hemophagocytic lymphohistiocytosis 5 Snapc2 familial hyperinsulinemic hypoglycemia 1 Polr3f familial retinoblastoma Rb1 fibroma Brf1 focal segmental glomerulosclerosis 5 Brf1 gastrointestinal stromal tumor Polr3c , Polr3gl , Pou2f1 , Rb1 genetic disease Brf1 , Polr1c , Polr1d , Polr2f , Polr3a , Polr3b , Polr3h , Rb1 , Snapc4 , Tbp Genitopatellar Syndrome Polr3a glioblastoma Rb1 glioblastoma proneural subtype Rb1 head and neck squamous cell carcinoma Polr1c , Rb1 Hearing Loss Bdp1 , Polr1c , Polr1d , Polr2f hemochromatosis type 2A Polr3gl hemolytic disease of the fetus Polr1c hepatocellular carcinoma Rb1 Hereditary Neoplastic Syndromes Polr3g , Rb1 hereditary nonpolyposis colorectal cancer type 4 Rb1 hereditary spastic paraplegia 54 Brf2 Hirschsprung Disease 1 Polr2f Hirschsprung's disease Polr2f holoprosencephaly Maf1 human immunodeficiency virus infectious disease Gtf3a Huntington's disease Tbp Hyperalgesia Crcp hypogonadism Polr3b hypogonadotropic hypogonadism Polr3b hypogonadotropic hypogonadism 2 with or without anosmia Brf2 hypogonadotropic hypogonadism 7 with or without anosmia Polr3b hypomyelinating leukodystrophy Polr3a hypomyelinating leukodystrophy 11 Polr1c hypomyelinating leukodystrophy 21 Polr3k hypomyelinating leukodystrophy 26 Polr1c hypomyelinating leukodystrophy 4 Polr3a hypomyelinating leukodystrophy 7 Polr3a , Polr3b hypomyelinating leukodystrophy 8 Polr3a , Polr3b hypotrichosis 8 Rb1 IMMUNODEFICIENCY 101 (VARICELLA ZOSTER VIRUS-SPECIFIC) Polr3f Immunodeficiency 103 Snapc4 immunodeficiency 39 Polr2l in situ carcinoma Rb1 infantile cerebellar-retinal degeneration Polr3h infantile Refsum disease Polr1c Insulin Resistance Rb1 intellectual disability Brf1 , Polr1c , Polr2f , Polr3b , Rb1 intestinal pseudo-obstruction Rb1 JABERI-ELAHI SYNDROME Polr1c Joubert syndrome 1 Snapc4 Kallmann syndrome Polr2f Kartagener syndrome Polr2k Kleefstra syndrome 1 Snapc4 Klinefelter syndrome Polr3b late onset Parkinson's disease Tbp Leigh disease Gtf3c4 , Gtf3c5 , Snapc4 leukodystrophy Polr3a long QT syndrome Snapc4 , Snapc5 lung adenocarcinoma Polr1d , Rb1 Lung Agenesis Polr1c lung non-small cell carcinoma Rb1 lung oat cell carcinoma Rb1 lung small cell carcinoma Rb1 Mandibulofacial Dysostosis Polr1c , Polr1d medulloblastoma Rb1 melanoma Snapc5 metachromatic leukodystrophy Polr3a mitochondrial DNA depletion syndrome 5 Rb1 mucolipidosis type IV Snapc2 myoclonic dystonia 26 Polr2f Neoplasm Metastasis Rb1 neurodegeneration with brain iron accumulation Polr1c neurodegeneration with brain iron accumulation 2A Polr2f NEURODEVELOPMENTAL DISORDER WITH MOTOR REGRESSION, PROGRESSIVE SPASTIC PARAPLEGIA, AND OROMOTOR DYSFUNCTION Snapc4 Neurodevelopmental Disorders Bdp1 , Gtf3c3 , Polr3g , Sub1 neuronal ceroid lipofuscinosis Gtf3c1 , Polr2l , Snapc5 neutropenia Polr3c Noonan syndrome Snapc5 obesity Rb1 Olfaction Disorders Polr2f oligodendroglioma Rb1 optic atrophy 9 Polr3h osteosarcoma Rb1 ovarian cancer Rb1 Ovarian Neoplasms Rb1 pancreatic cancer Rb1 paraplegia Brf2 parathyroid carcinoma Polr3c , Polr3gl , Pou2f1 PCWH syndrome Polr2f Peutz-Jeghers syndrome Polr2e Phyllodes Tumor Rb1 Pituitary Neoplasms Rb1 pleomorphic xanthoastrocytoma Crcp primary ciliary dyskinesia Polr1c primary ciliary dyskinesia 12 Polr1c primary ciliary dyskinesia 28 Polr2k primary coenzyme Q10 deficiency 7 Gtf3c4 , Gtf3c5 , Snapc4 primary ovarian insufficiency Polr3h progressive leukoencephalopathy with ovarian failure Polr1c prostate cancer Brf2 , Rb1 Prostatic Neoplasms Rb1 Rafiq syndrome Gtf3c4 , Gtf3c5 , Snapc4 RASopathy Snapc5 renal cell carcinoma Rb1 retinoblastoma Rb1 schizophrenia Polr3c , Polr3e , Polr3gl , Tbp sciatic neuropathy Crcp Segawa Syndrome, Autosomal Recessive Polr2l seminoma Rb1 sensorineural hearing loss Brf1 Sezary's disease Rb1 SHORT STATURE, OLIGODONTIA, DYSMORPHIC FACIES, AND MOTOR DELAY Polr3gl sleep apnea Tbp small cell carcinoma Rb1 spastic ataxia Polr3a Spinal Cord Injuries Tbp spinocerebellar ataxia type 17 Tbp Spinocerebellar Ataxias Tbp spondyloepimetaphyseal dysplasia with joint laxity Polr1c squamous cell carcinoma Rb1 Stevens-Johnson syndrome Rb1 Stomach Neoplasms Polr3k substance-related disorder Polr1d Tatton-Brown-Rahman syndrome Gtf3c2 thrombocytopenia-absent radius syndrome Polr3c , Polr3gl Tracheoesophageal Fistula Gtf3c1 Treacher Collins syndrome Polr1d Treacher Collins syndrome 2 Polr1d Treacher Collins syndrome 3 Polr1c trilateral retinoblastoma Rb1 tuberous sclerosis 1 Gtf3c4 , Gtf3c5 , Snapc4 type 1 diabetes mellitus Tbp urinary bladder cancer Rb1 Urinary Bladder Neoplasm Rb1 Van der Hoeve Halbertsma Waardenburg Gualdi Syndrome Polr2f Waardenburg syndrome Polr2f Waardenburg syndrome type 1 Polr2f Waardenburg syndrome type 2A Polr2f Waardenburg syndrome type 2E Polr2f Waardenburg syndrome type 4A Polr2f Waardenburg syndrome type 4C Polr2f Wiedemann-Rautenstrauch syndrome Polr3a xeroderma pigmentosum Polr1c xeroderma pigmentosum variant type Polr1c Zellweger syndrome Polr1c