POLR3GL

Summary

POLR3GL (RNA polymerase III subunit GL, HGNC:28466) is a protein-coding gene on chromosome 1q21.1, encoding DNA-directed RNA polymerase III subunit RPC7-like (Q9BT43). DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.

Predicted to enable chromatin binding activity. Involved in transcription by RNA polymerase III. Located in nucleus. Part of RNA polymerase III complex.

Source: NCBI Gene 84265 — RefSeq curated summary.

At a glance

• Gene–disease (curated): short stature, oligodontia, dysmorphic facies, and motor delay (Moderate, GenCC)
• Clinical variants (ClinVar): 42 total — 3 pathogenic
• Phenotypes (HPO): 34
• MANE Select transcript: NM_032305

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28466
Approved symbol	POLR3GL
Name	RNA polymerase III subunit GL
Location	1q21.1
Locus type	gene with protein product
Status	Approved
Aliases	flj32422, MGC3200
Ensembl gene	ENSG00000121851
Ensembl biotype	protein_coding
OMIM	617457
Entrez	84265

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 retained_intron

ENST00000369313, ENST00000369314, ENST00000471706, ENST00000622508, ENST00000855562, ENST00000855563, ENST00000855564

RefSeq mRNA: 2 — MANE Select: NM_032305 NM_001330685, NM_032305

CCDS: CCDS72875, CCDS81367

Canonical transcript exons

ENST00000369314 — 8 exons

Exon	Start	End
ENSE00000826060	145977983	145978096
ENSE00000826061	145977778	145977851
ENSE00000826063	145977084	145977152
ENSE00000826064	145975307	145975436
ENSE00001449469	145978361	145978848
ENSE00003501352	145977483	145977539
ENSE00003603498	145974825	145974991
ENSE00003844799	145964690	145964768

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.4423 / max 470.4244, expressed in 1821 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4960	25.3977	1814
4961	16.0447	1802

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	97.12	gold quality
muscle of leg	UBERON:0001383	96.72	gold quality
skeletal muscle tissue	UBERON:0001134	96.02	gold quality
right atrium auricular region	UBERON:0006631	96.01	gold quality
granulocyte	CL:0000094	95.40	gold quality
heart left ventricle	UBERON:0002084	94.99	gold quality
heart	UBERON:0000948	94.90	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.59	gold quality
descending thoracic aorta	UBERON:0002345	94.56	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.53	gold quality
apex of heart	UBERON:0002098	94.37	gold quality
mucosa of stomach	UBERON:0001199	94.33	gold quality
muscle tissue	UBERON:0002385	94.29	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.13	gold quality
popliteal artery	UBERON:0002250	94.10	gold quality
tibial artery	UBERON:0007610	94.10	gold quality
lower esophagus	UBERON:0013473	94.09	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.00	gold quality
adipose tissue	UBERON:0001013	93.98	gold quality
left coronary artery	UBERON:0001626	93.96	gold quality
right adrenal gland	UBERON:0001233	93.91	gold quality
right adrenal gland cortex	UBERON:0035827	93.76	gold quality
thoracic aorta	UBERON:0001515	93.74	gold quality
ascending aorta	UBERON:0001496	93.69	gold quality
spleen	UBERON:0002106	93.68	gold quality
left adrenal gland	UBERON:0001234	93.61	gold quality
left adrenal gland cortex	UBERON:0035825	93.56	gold quality
right coronary artery	UBERON:0001625	93.53	gold quality
right lung	UBERON:0002167	93.50	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.42	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.77
E-MTAB-7606	no	570.20

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

25 targeting POLR3GL, 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-4533	100.00	69.48	2758
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-1911-3P	99.15	66.17	528
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-6731-3P	98.61	67.86	749
HSA-MIR-6867-3P	98.12	66.07	1305
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-5196-3P	97.57	65.98	979
HSA-MIR-3121-5P	97.30	66.62	1146
HSA-MIR-2355-3P	96.84	68.54	909
HSA-MIR-4280	96.44	67.69	473

Literature-anchored findings (GeneRIF, showing 2)

• Depletion of POLR3G selectively triggers proliferative arrest and differentiation of prostate cancer cells, responses not elicited when POLR3GL is depleted. (PMID:30820548)
• Structural insights into transcriptional regulation of human RNA polymerase III. (PMID:33558766)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

DNA-directed RNA polymerase III subunit RPC7-like — Q9BT43 (reviewed: Q9BT43)

Alternative names: DNA-directed RNA polymerase III subunit G-like, RNA polymerase III 32 kDa beta subunit

All UniProt accessions (2): A6NGX6, Q9BT43

UniProt curated annotations — full annotation on UniProt →

Function. DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific peripheric component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs.

Subunit / interactions. Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits. Pol III exists as two alternative complexes defined by the mutually exclusive incorporation of subunit POLR3G/RPC7alpha or POLR3GL/RPC7beta. Found in a trimeric complex with POLR3C/RPC3 and POLR3F/RPC6. Directly interacts with POLR3C.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed. Expressed in CD4-positive T cells.

Disease relevance. Short stature, oligodontia, dysmorphic facies, and motor delay (SOFM) [MIM:619234] An autosomal recessive disorder with phenotypic variability. The main clinical features include endosteal hyperostosis, short stature, oligodontia, mild facial dysmorphisms, and delayed motor development. Some patients show progeroid features. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the eukaryotic RPC7 RNA polymerase subunit family.

RefSeq proteins (2): NP_001317614, NP_115681* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024661	RNA_pol_III_Rpc31	Family

Pfam: PF11705

UniProt features (6 total): compositionally biased region 3, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5AFQ	X-RAY DIFFRACTION	7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BT43-F1	71.38	0.18

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: 201 (showing top): REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_INITIATION_FROM_TYPE_3_PROMOTER, REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_TERMINATION, REACTOME_INNATE_IMMUNE_SYSTEM, BENPORATH_ES_WITH_H3K27ME3, MYOGENIN_Q6, CCAWYNNGAAR_UNKNOWN, REACTOME_RNA_POLYMERASE_III_CHAIN_ELONGATION, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, MAZ_Q6, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, CAGCTG_AP4_Q5, KEGG_CYTOSOLIC_DNA_SENSING_PATHWAY, MYOD_01, WCTCNATGGY_UNKNOWN, WTGAAAT_UNKNOWN

GO Biological Process (1): transcription by RNA polymerase III (GO:0006383)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), RNA polymerase III complex (GO:0005666), cytosol (GO:0005829)

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	2
DNA-templated transcription	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
DNA-directed RNA polymerase complex	1
nuclear protein-containing complex	1
cytoplasm	1

Protein interactions and networks

STRING

846 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLR3GL	POLR3C	Q9BUI4	855
POLR3GL	POLR3A	O14802	811
POLR3GL	POLR3K	Q9Y2Y1	772
POLR3GL	POLR3B	Q9NW08	738
POLR3GL	POLR3H	Q9Y535	732
POLR3GL	POLR3F	Q9H1D9	699
POLR3GL	POLR3D	P05423	643
POLR3GL	POLR3E	Q9NVU0	594
POLR3GL	LIX1L	Q8IVB5	580
POLR3GL	ANKRD34A	Q69YU3	578
POLR3GL	ANKRD35	Q8N283	572
POLR3GL	GPHRA	B7ZAQ6	539
POLR3GL	CRCP	O75575	534
POLR3GL	PRKAB2	O43741	527
POLR3GL	BDP1	A6H8Y1	507

IntAct

77 interactions, top by confidence:

A	B	Type	Score
POLR3GL	POLR3C	psi-mi:“MI:0914”(association)	0.930
POLR3C	POLR3GL	psi-mi:“MI:0915”(physical association)	0.930
POLR3GL	POLR3C	psi-mi:“MI:0915”(physical association)	0.930
POLR3F	POLR3GL	psi-mi:“MI:0915”(physical association)	0.820
POLR3GL	CCND3	psi-mi:“MI:0915”(physical association)	0.780
CCND3	POLR3GL	psi-mi:“MI:0915”(physical association)	0.780
POLR3GL	POLR3A	psi-mi:“MI:0914”(association)	0.730
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
POLR3D	POLR3A	psi-mi:“MI:0914”(association)	0.640
TFCP2	POLR3GL	psi-mi:“MI:0915”(physical association)	0.560
POLR3GL	YAF2	psi-mi:“MI:0915”(physical association)	0.560
M1AP	POLR3GL	psi-mi:“MI:0915”(physical association)	0.560
PAX6	POLR3GL	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (87): POLR3GL (Two-hybrid), POLR3GL (Two-hybrid), POLR3GL (Affinity Capture-MS), POLR3GL (Affinity Capture-MS), POLR3F (Affinity Capture-MS), POLR3H (Affinity Capture-MS), POLR3E (Affinity Capture-MS), POLR3C (Affinity Capture-MS), POLR3B (Affinity Capture-MS), POLR3D (Affinity Capture-MS), CRCP (Affinity Capture-MS), POLR3K (Affinity Capture-MS), POLR3A (Affinity Capture-MS), POLR1C (Affinity Capture-MS), POLR2L (Affinity Capture-MS)

ESM2 similar proteins: A2BD83, F4HQA1, F4HRV8, F4ICK8, O43290, P21675, P35269, Q04870, Q13435, Q15545, Q1RMR0, Q2HJG8, Q2KJ14, Q3THK3, Q3UJB0, Q4R5A5, Q4U0S5, Q4V886, Q52KV5, Q53F19, Q5EA53, Q5HZB6, Q5R4D6, Q5R7L9, Q5RAX0, Q5XIW8, Q5XJE5, Q5ZHP7, Q5ZIH9, Q5ZIM6, Q5ZM19, Q641X2, Q6AY96, Q6NYV9, Q6P2Y1, Q6R1L1, Q80UV9, Q811X5, Q8BZR9, Q8CFC7

Diamond homologs: O15318, Q1RMR0, Q6NXY9, Q8R0C0, Q9BT43

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 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	13	374.9×	7e-32
RNA Polymerase III Transcription Termination	13	293.4×	2e-30
RNA Polymerase III Transcription Initiation From Type 2 Promoter	14	269.2×	7e-32
RNA Polymerase III Transcription Initiation From Type 1 Promoter	14	259.6×	7e-32
RNA Polymerase III Transcription Initiation From Type 3 Promoter	14	259.6×	7e-32
RNA Polymerase III Transcription Initiation	14	213.7×	2e-30
RNA Polymerase III Transcription	14	207.6×	2e-30
RNA Polymerase III Abortive And Retractive Initiation	14	177.2×	3e-29

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase III	5	132.1×	4e-08
positive regulation of interferon-beta production	5	67.6×	4e-07
defense response to virus	8	19.1×	3e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	28
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1459111	NC_000001.10:g.(?145414782)(145610584_?)del	Pathogenic
617676	NM_032305.3(POLR3GL):c.-41-1G>A	Pathogenic
980942	GRCh37/hg19 1q21.1-21.2(chr1:144887445-148801960)x1	Pathogenic

SpliceAI

759 predictions. Top by Δscore:

Variant	Effect	Δscore
1:145974990:C:CC	donor_gain	1.0000
1:145974991:A:AC	donor_gain	1.0000
1:145975304:C:CC	acceptor_gain	1.0000
1:145975307:GGG:G	acceptor_gain	1.0000
1:145975435:CCT:C	donor_gain	1.0000
1:145975435:CCTCT:C	donor_gain	1.0000
1:145975436:A:C	donor_loss	1.0000
1:145975437:GACC:G	donor_loss	1.0000
1:145975437:GACCT:G	donor_loss	1.0000
1:145975438:TGA:T	donor_loss	1.0000
1:145977535:T:A	donor_gain	1.0000
1:145977538:C:CC	donor_gain	1.0000
1:145977538:CGTT:C	donor_gain	1.0000
1:145977538:CGTTC:C	donor_gain	1.0000
1:145977539:A:AC	donor_gain	1.0000
1:145977539:ACGTT:A	donor_gain	1.0000
1:145977965:A:AC	acceptor_gain	1.0000
1:145977965:A:C	acceptor_gain	1.0000
1:145977969:A:AC	acceptor_gain	1.0000
1:145977969:A:C	acceptor_gain	1.0000
1:145977975:G:GC	acceptor_gain	1.0000
1:145977977:A:AC	acceptor_gain	1.0000
1:145977977:A:C	acceptor_gain	1.0000
1:145977978:CATG:C	acceptor_gain	1.0000
1:145978051:T:TA	donor_gain	1.0000
1:145978060:T:TA	donor_gain	1.0000
1:145978070:C:CC	donor_gain	1.0000
1:145978070:CT:C	donor_gain	1.0000
1:145978070:CTCTT:C	donor_gain	1.0000
1:145978071:A:AC	donor_gain	1.0000

AlphaMissense

1417 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:145978385:T:C	F199L	1.000
1:145978387:T:A	F199L	1.000
1:145978387:T:G	F199L	1.000
1:145975368:T:C	L63P	0.999
1:145978367:G:C	D193H	0.999
1:145978370:T:C	Y194H	0.999
1:145975380:T:C	L67P	0.998
1:145977507:T:C	L117P	0.998
1:145978368:A:T	D193V	0.998
1:145978386:T:C	F199S	0.998
1:145978386:T:G	F199C	0.998
1:145977095:T:G	Y90D	0.997
1:145978368:A:C	D193A	0.997
1:145978382:T:G	Y198D	0.997
1:145978385:T:G	F199V	0.997
1:145977143:T:A	W106R	0.996
1:145977143:T:C	W106R	0.996
1:145977495:T:C	L113P	0.996
1:145978368:A:G	D193G	0.996
1:145978369:T:A	D193E	0.996
1:145978369:T:G	D193E	0.996
1:145978385:T:A	F199I	0.996
1:145978395:G:T	G202V	0.996
1:145977485:T:A	W110R	0.995
1:145977485:T:C	W110R	0.995
1:145977847:T:C	L151P	0.995
1:145978393:T:A	N201K	0.995
1:145978393:T:G	N201K	0.995
1:145978394:G:A	G202R	0.995
1:145978394:G:C	G202R	0.995

dbSNP variants (sampled 300 via entrez): RS1000035419 (1:145967819 C>T), RS1000151176 (1:145968194 G>A), RS1000266708 (1:145939865 C>T), RS1000348265 (1:145975244 G>A), RS1000606035 (1:145938415 G>A), RS1000857081 (1:145960130 T>C,G), RS1000863760 (1:145932128 G>A), RS1000906360 (1:145946325 A>T), RS1000964074 (1:145952900 C>T), RS1000992049 (1:145952650 C>T), RS1001123053 (1:145945638 C>G,T), RS1001188126 (1:145931594 A>C,G,T), RS1001248965 (1:145931804 C>T), RS1001289187 (1:145959756 G>A), RS1001334800 (1:145974537 A>G,T)

Disease associations

OMIM: gene MIM:617457 | disease phenotypes: MIM:274000, MIM:619234

GenCC curated gene-disease

Disease	Classification	Inheritance
short stature, oligodontia, dysmorphic facies, and motor delay	Moderate	Autosomal recessive

Mondo (3): thrombocytopenia-absent radius syndrome (MONDO:0010121), hyperostosis (MONDO:0002185), short stature, oligodontia, dysmorphic facies, and motor delay (MONDO:0030992)

Orphanet (1): Thrombocytopenia-absent radius syndrome (Orphanet:3320)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000252	Microcephaly
HP:0000319	Smooth philtrum
HP:0000483	Astigmatism
HP:0000520	Proptosis
HP:0000582	Upslanted palpebral fissure
HP:0000646	Amblyopia
HP:0000677	Oligodontia
HP:0000821	Hypothyroidism
HP:0000823	Delayed puberty
HP:0000824	Decreased response to growth hormone stimulation test
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001270	Motor delay
HP:0001382	Joint hypermobility
HP:0001510	Growth delay
HP:0001537	Umbilical hernia
HP:0001730	Progressive hearing impairment
HP:0001762	Talipes equinovarus
HP:0001770	Toe syndactyly
HP:0001847	Long hallux
HP:0002079	Hypoplasia of the corpus callosum
HP:0002313	Spastic paraparesis
HP:0002938	Lumbar hyperlordosis
HP:0003418	Back pain
HP:0003701	Proximal muscle weakness
HP:0004322	Short stature
HP:0005617	Bilateral camptodactyly
HP:0007787	Posterior subcapsular cataract

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D015576	Hyperostosis	C05.116.540
C536940	Absent radii and thrombocytopenia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects expression, affects cotreatment, increases expression	2
Valproic Acid	decreases expression	2
Cyclosporine	decreases expression	2
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
trichostatin A	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
jinfukang	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Silicon Dioxide	decreases expression	1
Thiram	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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