POLR3G

Summary

POLR3G (RNA polymerase III subunit G, HGNC:30075) is a protein-coding gene on chromosome 5q14.3, encoding DNA-directed RNA polymerase III subunit RPC7 (O15318). DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.

Enables chromatin binding activity. Involved in positive regulation of innate immune response; positive regulation of interferon-beta production; and transcription by RNA polymerase III. Acts upstream of or within cell population proliferation. Located in cytosol and nuclear body. Part of RNA polymerase III complex.

Source: NCBI Gene 10622 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 39 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_006467

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30075
Approved symbol	POLR3G
Name	RNA polymerase III subunit G
Location	5q14.3
Locus type	gene with protein product
Status	Approved
Aliases	RPC32, RPC7, C31
Ensembl gene	ENSG00000113356
Ensembl biotype	protein_coding
OMIM	617456
Entrez	10622

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 33 protein_coding, 1 nonsense_mediated_decay

ENST00000399107, ENST00000503373, ENST00000504930, ENST00000505345, ENST00000512239, ENST00000514483, ENST00000651687, ENST00000859024, ENST00000859025, ENST00000859026, ENST00000859027, ENST00000859028, ENST00000859029, ENST00000912712, ENST00000912713, ENST00000912714, ENST00000912715, ENST00000912716, ENST00000912717, ENST00000912718, ENST00000912719, ENST00000912720, ENST00000912721, ENST00000912722, ENST00000912724, ENST00000912725, ENST00000912726, ENST00000912727, ENST00000912728, ENST00000912729, ENST00000912730, ENST00000912731, ENST00000912732, ENST00000959308

RefSeq mRNA: 5 — MANE Select: NM_006467 NM_001370351, NM_001370352, NM_001370353, NM_001370354, NM_006467

CCDS: CCDS43337

Canonical transcript exons

ENST00000651687 — 8 exons

Exon	Start	End
ENSE00001483693	90474864	90475020
ENSE00003847311	90512053	90514557
ENSE00003890962	90488000	90488129
ENSE00003894315	90501906	90501988
ENSE00003894583	90495677	90495733
ENSE00003894667	90485525	90485684
ENSE00003894847	90497656	90497706
ENSE00003895786	90506528	90506674

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 92.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.6075 / max 419.3062, expressed in 1482 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57512	7.5711	1276
57511	2.7212	1042
57513	0.3152	116

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsal root ganglion	UBERON:0000044	92.53	gold quality
sural nerve	UBERON:0015488	89.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.62	gold quality
tendon of biceps brachii	UBERON:0008188	89.00	gold quality
secondary oocyte	CL:0000655	88.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.34	gold quality
medial globus pallidus	UBERON:0002477	84.31	gold quality
monocyte	CL:0000576	84.24	gold quality
mononuclear cell	CL:0000842	83.48	gold quality
oocyte	CL:0000023	82.72	gold quality
trigeminal ganglion	UBERON:0001675	82.19	gold quality
leukocyte	CL:0000738	82.11	gold quality
buccal mucosa cell	CL:0002336	81.61	gold quality
globus pallidus	UBERON:0001875	79.53	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	79.40	gold quality
type B pancreatic cell	CL:0000169	78.61	gold quality
spinal cord	UBERON:0002240	77.65	gold quality
gingival epithelium	UBERON:0001949	73.91	silver quality
oviduct epithelium	UBERON:0004804	73.79	gold quality
tendon	UBERON:0000043	73.43	gold quality
tongue squamous epithelium	UBERON:0006919	73.42	gold quality
cerebellar hemisphere	UBERON:0002245	72.68	gold quality
cerebellar cortex	UBERON:0002129	72.64	gold quality
substantia nigra	UBERON:0002038	72.60	gold quality
gingiva	UBERON:0001828	72.59	silver quality
esophagus mucosa	UBERON:0002469	72.47	gold quality
pancreatic ductal cell	CL:0002079	72.40	silver quality
lower esophagus mucosa	UBERON:0035834	72.24	gold quality
stromal cell of endometrium	CL:0002255	72.22	gold quality
right hemisphere of cerebellum	UBERON:0014890	72.17	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-109979	yes	430.14
E-MTAB-10018	yes	251.32
E-MTAB-9388	yes	14.09
E-ANND-3	no	4.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

198 targeting POLR3G, 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-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-5688	99.96	73.23	4504

Literature-anchored findings (GeneRIF, showing 7)

• Decreased levels of POLR3G result in loss of pluripotency and promote differentiation of human embryonic stem cells to all three germ layers but have no effect on cell apoptosis. (PMID:21898682)
• POLR3G regulates small non-coding RNAs and RNA splicing in human pluripotent stem cells. The primary function of POLR3G is in the maintenance rather than repression of transcription. (PMID:28494942)
• Depletion of POLR3G selectively triggers proliferative arrest and differentiation of prostate cancer cells, responses not elicited when POLR3GL is depleted. (PMID:30820548)
• FCER1A (rs7549785) and possibly POLR3G (rs7712322) are shown to be associated with peginterferon alfa-2a response in adult patients with chronic hepatitis B. (PMID:30972912)
• RNA polymerase III is required for the repair of DNA double-strand breaks by homologous recombination. (PMID:33626331)
• A cancer-associated RNA polymerase III identity drives robust transcription and expression of snaR-A noncoding RNA. (PMID:35637192)
• POLR3G promotes EMT via PI3K/AKT signaling pathway in bladder cancer. (PMID:37933949)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

DNA-directed RNA polymerase III subunit RPC7 — O15318 (reviewed: O15318)

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

All UniProt accessions (6): O15318, A0A7I2R591, D6R9U7, D6REQ0, D6RIT0, D6RJH6

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 (Pol III) which synthesizes small non-coding RNAs including 5S rRNA, snRNAs, tRNAs and miRNAs from at least 500 distinct genomic loci. Acts as a long tether that bridges POLR3C/RPC3-POLR3F/RPC6-POLR3G/RPC7 heterotrimer and the mobile stalk of Pol III, coordinating the dynamics of Pol III stalk and clamp modules during the transition from apo to elongation state. Pol III exists as two alternative complexes defined by the mutually exclusive incorporation of subunit POLR3G/RPC7alpha or POLR3GL/RPC7beta. POLR3G/RPC7alpha modulates Pol III transcriptome by specifically enhancing the transcription of snaR-A non-coding RNAs. At resting state, occupies the active site of apo Pol III and keeps Pol III in an autoinhibitory mode, preventing non-specific transcription. 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 complex consisting of 17 subunits: a ten-subunit horseshoe-shaped 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. Directly interacts with POLR3C/RPC62. Also found in a trimeric complex with POLR3C/RPC3 and POLR3GL.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Barely detectable in differentiated tissues. Expressed in embryonic stem cells and in other dividing cells, such as some tumor cell lines.

Induction. Induced by NANOG and POU5F1/OCT4. Negatively regulated by the interaction of microRNA MIR1305 with 3 miRNA responsive elements (miREs) in its 3’-UTR. Transcriptionally regulated by MYC. down-regulated upon cell differentiation.

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

RefSeq proteins (5): NP_001357280, NP_001357281, NP_001357282, NP_001357283, NP_006458* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024661	RNA_pol_III_Rpc31	Family

Pfam: PF11705

UniProt features (24 total): helix 5, compositionally biased region 5, strand 4, turn 4, sequence conflict 2, modified residue 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

28 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
8IUE	ELECTRON MICROSCOPY	4.1
9FSS	ELECTRON MICROSCOPY	4.14
9K3B	ELECTRON MICROSCOPY	4.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15318-F1	68.46	0.10

Functional residue map

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

Post-translational modifications (2): 133, 157

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: 220 (showing top): REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_INITIATION_FROM_TYPE_3_PROMOTER, REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_TERMINATION, HORIUCHI_WTAP_TARGETS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, YAGI_AML_WITH_INV_16_TRANSLOCATION, XU_HGF_TARGETS_REPRESSED_BY_AKT1_UP, REACTOME_RNA_POLYMERASE_III_CHAIN_ELONGATION, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, KEGG_CYTOSOLIC_DNA_SENSING_PATHWAY, PUJANA_CHEK2_PCC_NETWORK, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS

GO Biological Process (8): regulation of transcription by RNA polymerase III (GO:0006359), transcription by RNA polymerase III (GO:0006383), cell population proliferation (GO:0008283), positive regulation of interferon-beta production (GO:0032728), innate immune response (GO:0045087), positive regulation of innate immune response (GO:0045089), defense response to virus (GO:0051607), immune system process (GO:0002376)

GO Molecular Function (3): chromatin binding (GO:0003682), DNA-directed RNA polymerase activity (GO:0003899), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), RNA polymerase III complex (GO:0005666), cytosol (GO:0005829), nuclear body (GO:0016604), DNA-directed RNA polymerase complex (GO:0000428), cytoplasm (GO:0005737)

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
binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase III	1
DNA-templated transcription	1
cellular process	1
positive regulation of type I interferon production	1
interferon-beta production	1
regulation of interferon-beta production	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
RNA biosynthetic process	1
5’-3’ RNA polymerase activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
DNA-directed RNA polymerase complex	1
nuclear protein-containing complex	1
cytoplasm	1
nucleoplasm	1
intracellular membraneless organelle	1
RNA polymerase complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1102 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLR3G	POLR3C	Q9BUI4	992
POLR3G	POLR3F	Q9H1D9	972
POLR3G	POLR3D	P05423	870
POLR3G	POLR3B	Q9NW08	852
POLR3G	POLR3A	O14802	831
POLR3G	POLR3E	Q9NVU0	811
POLR3G	POLR3H	Q9Y535	804
POLR3G	POLR3K	Q9Y2Y1	802
POLR3G	CRCP	O75575	772
POLR3G	POLR1D	P0DPB6	720
POLR3G	GTF3C2	Q8WUA4	627
POLR3G	BDP1	A6H8Y1	622
POLR3G	POLR2H	P52434	609
POLR3G	POLR1C	O15160	572
POLR3G	GTF3C5	Q9Y5Q8	570

IntAct

73 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
POLR3G	POLR3C	psi-mi:“MI:0914”(association)	0.800
POLR3C	POLR3G	psi-mi:“MI:0915”(physical association)	0.800
POLR3G	POLR3C	psi-mi:“MI:0915”(physical association)	0.800
POLR3D	POLR3G	psi-mi:“MI:0914”(association)	0.730
POLR3GL	POLR3A	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
POLR3F	POLR3G	psi-mi:“MI:0915”(physical association)	0.620
POLR1C	POLR3A	psi-mi:“MI:0914”(association)	0.530
POLR3H	POLR3A	psi-mi:“MI:0914”(association)	0.530
MAF1	POLR3A	psi-mi:“MI:0914”(association)	0.530

BioGRID (85): POLR3G (Affinity Capture-MS), POLR3G (Co-fractionation), POLR3G (Co-fractionation), POLR3G (Co-fractionation), POLR3G (Co-fractionation), POLR3G (Co-fractionation), POLR3G (Co-fractionation), POLR3G (Co-fractionation), POLR3G (Co-fractionation), POLR3H (Co-fractionation), POLR3G (Affinity Capture-MS), POLR3G (Affinity Capture-MS), POLR3G (Affinity Capture-MS), POLR3G (Affinity Capture-MS), POLR3G (Affinity Capture-MS)

ESM2 similar proteins: B0WCZ5, F4HVZ5, F4IDY7, F4IP06, O00566, O15318, O48713, O94416, O95391, P17890, P51123, Q04870, Q05913, Q0VC06, Q0ZB73, Q10191, Q17431, Q1RMR0, Q21278, Q3KQD1, Q3ZBE5, Q4R4P2, Q4V838, Q56P03, Q5BU09, Q5EA98, Q5R8B2, Q5U3F2, Q5U3J8, Q5ZIG2, Q68FR7, Q6GNJ8, Q6NXY9, Q7KN79, Q7Q566, Q80ZG5, Q810V0, Q8BHJ9, Q8R0C0, Q8WZJ8

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

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
POLR3G	“form complex”	“RNA Polymerase III”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 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	282.0×	3e-38
RNA Polymerase III Transcription Termination	16	220.7×	2e-35
RNA Polymerase III Transcription Initiation From Type 2 Promoter	18	211.5×	8e-39
RNA Polymerase III Transcription Initiation From Type 1 Promoter	18	203.9×	8e-39
RNA Polymerase III Transcription Initiation From Type 3 Promoter	18	203.9×	8e-39
RNA Polymerase III Transcription Initiation	18	167.9×	8e-37
RNA Polymerase III Transcription	18	163.1×	1e-36
RNA Polymerase III Abortive And Retractive Initiation	18	139.3×	5e-35

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase III	7	124.7×	2e-11
positive regulation of interferon-beta production	5	45.6×	6e-06
defense response to virus	8	12.9×	9e-06
transcription by RNA polymerase II	7	11.5×	9e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1457 predictions. Top by Δscore:

Variant	Effect	Δscore
5:90473837:ACCAT:A	donor_gain	1.0000
5:90473838:CCATC:C	donor_gain	1.0000
5:90475016:AGCAG:A	donor_loss	1.0000
5:90475018:CAG:C	donor_loss	1.0000
5:90475019:AGG:A	donor_loss	1.0000
5:90475020:GG:G	donor_loss	1.0000
5:90475021:G:GA	donor_loss	1.0000
5:90475030:G:GT	donor_gain	1.0000
5:90485137:TCTTA:T	donor_gain	1.0000
5:90485803:A:T	donor_gain	1.0000
5:90487989:A:AG	acceptor_gain	1.0000
5:90487990:A:G	acceptor_gain	1.0000
5:90487995:A:G	acceptor_gain	1.0000
5:90487997:CA:C	acceptor_loss	1.0000
5:90487998:A:AG	acceptor_gain	1.0000
5:90487998:A:AT	acceptor_loss	1.0000
5:90487998:AG:A	acceptor_gain	1.0000
5:90487999:G:GT	acceptor_gain	1.0000
5:90487999:GG:G	acceptor_gain	1.0000
5:90488125:ACAAG:A	donor_loss	1.0000
5:90488126:CAAG:C	donor_loss	1.0000
5:90488127:AAG:A	donor_loss	1.0000
5:90488128:AGGT:A	donor_loss	1.0000
5:90488130:GT:G	donor_loss	1.0000
5:90488131:T:G	donor_loss	1.0000
5:90473841:T:A	donor_gain	0.9900
5:90475014:G:GT	donor_gain	0.9900
5:90475022:T:A	donor_loss	0.9900
5:90485117:C:G	donor_gain	0.9900
5:90485122:A:G	donor_gain	0.9900

AlphaMissense

1507 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:90512077:T:C	F204L	0.993
5:90512079:T:A	F204L	0.993
5:90512079:T:G	F204L	0.993
5:90485607:T:C	F14L	0.989
5:90485609:T:A	F14L	0.989
5:90485609:T:G	F14L	0.989
5:90512062:T:C	Y199H	0.987
5:90512059:G:C	D198H	0.984
5:90495724:T:A	W99R	0.983
5:90495724:T:C	W99R	0.983
5:90512058:T:A	N197K	0.982
5:90512058:T:G	N197K	0.982
5:90485608:T:C	F14S	0.980
5:90512060:A:T	D198V	0.979
5:90512107:A:C	S214R	0.978
5:90512109:T:A	S214R	0.978
5:90512109:T:G	S214R	0.978
5:90512134:T:C	Y223H	0.978
5:90512060:A:C	D198A	0.977
5:90485679:T:C	F38L	0.975
5:90485681:T:A	F38L	0.975
5:90485681:T:G	F38L	0.975
5:90512078:T:G	F204C	0.975
5:90485626:G:A	G20E	0.974
5:90512061:C:A	D198E	0.974
5:90512061:C:G	D198E	0.974
5:90485590:G:A	G8E	0.973
5:90497658:T:A	W103R	0.973
5:90497658:T:C	W103R	0.973
5:90497668:T:C	L106P	0.971

dbSNP variants (sampled 300 via entrez): RS1000066480 (5:90505064 G>A), RS1000241739 (5:90497304 A>G), RS1000302982 (5:90500126 A>C), RS1000315216 (5:90484214 A>G), RS1000402294 (5:90479294 A>G), RS1000485020 (5:90493436 G>A,T), RS1000577383 (5:90507211 A>C), RS1000624819 (5:90484565 A>C), RS1000819990 (5:90491692 C>G), RS1000865865 (5:90473441 G>A,C), RS1000882163 (5:90473685 G>A,C), RS1000947824 (5:90512461 TCTTG>T), RS1000994281 (5:90473924 G>A), RS1001048185 (5:90498545 A>G), RS1001110458 (5:90479171 T>A)

Disease associations

OMIM: gene MIM:617456 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (1): autism (MONDO:0005260)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001186_1	Nevirapine-induced rash	5.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2562519	Toxicity	3	nevirapine	HIV infectious disease

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2562519	POLR3G	3	3.25	1	nevirapine

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	6
methylmercuric chloride	increases expression, affects cotreatment	4
trichostatin A	affects cotreatment, increases expression	4
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	3
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	3
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	increases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cisplatin	decreases expression	2
Estradiol	increases expression	2
Tretinoin	decreases expression	2
aristolochic acid I	decreases expression	1
afuresertib	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol A	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	increases expression	1
nickel sulfate	increases expression	1
vanadyl sulfate	increases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
bisphenol AF	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms