POLR3F

Summary

POLR3F (RNA polymerase III subunit F, HGNC:15763) is a protein-coding gene on chromosome 20p11.23, encoding DNA-directed RNA polymerase III subunit RPC6 (Q9H1D9). DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. It is a common-essential gene (DepMap: required in 99.4% of cancer cell lines).

The protein encoded by this gene is one of more than a dozen subunits forming eukaryotic RNA polymerase III (RNA Pol III), which transcribes 5S ribosomal RNA and tRNA genes. This protein has been shown to bind both TFIIIB90 and TBP, two subunits of RNA polymerase III transcription initiation factor IIIB (TFIIIB). Unlike most of the other RNA Pol III subunits, the encoded protein is unique to this polymerase. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10621 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 101 (varicella zoster virus-specific) (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 187 total — 1 pathogenic
• Phenotypes (HPO): 3
• Cancer dependency (DepMap): dependent in 99.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_006466

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15763
Approved symbol	POLR3F
Name	RNA polymerase III subunit F
Location	20p11.23
Locus type	gene with protein product
Status	Approved
Aliases	RPC39, RPC6, C34
Ensembl gene	ENSG00000132664
Ensembl biotype	protein_coding
OMIM	617455
Entrez	10621

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 12 protein_coding, 6 nonsense_mediated_decay, 5 retained_intron

ENST00000377603, ENST00000461589, ENST00000462997, ENST00000475192, ENST00000489753, ENST00000497333, ENST00000697645, ENST00000697646, ENST00000697647, ENST00000697648, ENST00000697649, ENST00000697650, ENST00000697651, ENST00000697652, ENST00000697653, ENST00000697654, ENST00000697655, ENST00000697656, ENST00000697657, ENST00000697658, ENST00000697659, ENST00000697660, ENST00000855082

RefSeq mRNA: 3 — MANE Select: NM_006466 NM_001282526, NM_001410821, NM_006466

CCDS: CCDS13135, CCDS93015, CCDS93016

Canonical transcript exons

ENST00000377603 — 9 exons

Exon	Start	End
ENSE00003551367	18473391	18473458
ENSE00003566168	18472842	18472909
ENSE00003618165	18475075	18475187
ENSE00003971315	18483481	18484646
ENSE00003971326	18480402	18480509
ENSE00003971330	18480038	18480181
ENSE00003971334	18481619	18481810
ENSE00003971341	18467390	18467568
ENSE00003971346	18468944	18469061

Expression profiles

Bgee: expression breadth ubiquitous, 221 present calls, max score 90.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.5801 / max 157.8898, expressed in 1808 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183685	15.5801	1808

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	90.82	gold quality
cerebellar cortex	UBERON:0002129	90.63	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.59	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.69	gold quality
cerebellum	UBERON:0002037	88.52	gold quality
calcaneal tendon	UBERON:0003701	87.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.67	gold quality
adrenal tissue	UBERON:0018303	85.23	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.72	gold quality
cortical plate	UBERON:0005343	84.57	gold quality
tendon	UBERON:0000043	84.36	gold quality
ganglionic eminence	UBERON:0004023	84.19	gold quality
right frontal lobe	UBERON:0002810	83.53	gold quality
ventricular zone	UBERON:0003053	83.30	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.07	gold quality
monocyte	CL:0000576	82.92	gold quality
prefrontal cortex	UBERON:0000451	82.71	gold quality
mononuclear cell	CL:0000842	82.55	gold quality
leukocyte	CL:0000738	82.45	gold quality
muscle of leg	UBERON:0001383	82.12	gold quality
gastrocnemius	UBERON:0001388	81.98	gold quality
descending thoracic aorta	UBERON:0002345	81.66	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.50	gold quality
cingulate cortex	UBERON:0003027	81.49	gold quality
caudate nucleus	UBERON:0001873	81.19	gold quality
anterior cingulate cortex	UBERON:0009835	81.19	gold quality
tibial artery	UBERON:0007610	81.09	gold quality
popliteal artery	UBERON:0002250	81.08	gold quality
aorta	UBERON:0000947	80.89	gold quality
thoracic aorta	UBERON:0001515	80.87	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting POLR3F, 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-3185	99.99	68.12	1959
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 1)

• We also show that endogenous microDNA associate with RNA polymerases subunits, POLR2H and POLR3F. Together, these results suggest that microDNA may modulate gene expression through the production of both known and novel regulatory small RNA. (PMID:30828735)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	polr3f	ENSDARG00000012572
mus_musculus	Polr3f	ENSMUSG00000027427
rattus_norvegicus	Polr3f	ENSRNOG00000007548
drosophila_melanogaster	Polr3F	FBGN0038951
caenorhabditis_elegans	W09C3.4	WBGENE00021112

Protein

Protein identifiers

DNA-directed RNA polymerase III subunit RPC6 — Q9H1D9 (reviewed: Q9H1D9)

Alternative names: DNA-directed RNA polymerase III subunit F, RNA polymerase III 39 kDa subunit

All UniProt accessions (15): Q9H1D9, A0A8V8TL45, A0A8V8TL49, A0A8V8TL53, A0A8V8TL66, A0A8V8TL69, A0A8V8TL74, A0A8V8TLI4, A0A8V8TLJ3, A0A8V8TMI8, A0A8V8TMJ7, A0A8V8TMS0, A0A8V8TMS5, A0A8V8TMT0, Q05DB8

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. Part of POLR3C/RPC3-POLR3F/RPC6-POLR3G/RPC7 heterotrimer that coordinates the dynamics of Pol III stalk and clamp modules during the transition from apo to elongation state. Pol III plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses, including varicella zoster virus. Acts as a nuclear and cytosolic DNA sensor detecting AT-rich DNA, 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. Preferentially binds double-stranded DNA (dsDNA).

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. Interacts with TBP and TFIIIB90 and GTF3C4. Interacts with MAF1. As part of the RNA polymerase III complex, interacts with PKP2.

Subcellular location. Nucleus.

Disease relevance. Immunodeficiency 101, varicella zoster virus-specific (IMD101) [MIM:619872] An autosomal dominant immunologic disorder characterized by reactivation of varicella zoster virus (VZV) infection in adulthood after primary childhood infection with VZV. The viral reactivation manifests as central nervous system vasculitis with stroke-like episodes and lacunar infarcts on brain imaging. Features include headache, hemiparesis, impaired balance, and other neurologic signs. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. The [4FE-4S] cluster-binding domain adopts a globular structure that serves as an interaction hub that connects the POLR3C/RPC3-POLR3F/RPC6-POLR3G/RPC7 heterotrimer to the Pol III core.

Similarity. Belongs to the eukaryotic RPC34/RPC39 RNA polymerase subunit family.

RefSeq proteins (3): NP_001269455, NP_001397750, NP_006457* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007832	RNA_pol_Rpc34	Family
IPR016049	RNA_pol_Rpc34-like	Family
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily

Pfam: PF05158

UniProt features (45 total): helix 17, strand 12, binding site 4, sequence conflict 3, mutagenesis site 2, cross-link 2, initiator methionine 1, chain 1, turn 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

31 structures, top 30 by resolution.

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
2DK5	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H1D9-F1	85.10	0.44

Functional residue map

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

Ligand- & substrate-binding residues (4): 287; 290; 296; 307

Post-translational modifications (3): 2, 5, 7

Mutagenesis-validated functional residues (2):

Position	Phenotype
137–140	strongly impaired dsdna-binding. no effect on interaction with polr3c.
173–175	strongly impaired dsdna-binding. no effect on interaction with polr3c.

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: 203 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, 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, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, MORF_BRCA1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, MORF_RAD51L3

GO Biological Process (7): regulation of transcription by RNA polymerase III (GO:0006359), transcription by RNA polymerase III (GO:0006383), 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 (5): double-stranded DNA binding (GO:0003690), DNA-directed RNA polymerase activity (GO:0003899), 4 iron, 4 sulfur cluster binding (GO:0051539), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (6): nucleoplasm (GO:0005654), RNA polymerase III complex (GO:0005666), cytosol (GO:0005829), DNA-directed RNA polymerase complex (GO:0000428), nucleus (GO:0005634), 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
regulation of DNA-templated transcription	1
transcription by RNA polymerase III	1
DNA-templated transcription	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
DNA binding	1
RNA biosynthetic process	1
5’-3’ RNA polymerase activity	1
iron-sulfur cluster binding	1
nucleic acid binding	1
binding	1
nuclear lumen	1
DNA-directed RNA polymerase complex	1
nuclear protein-containing complex	1
cytoplasm	1
RNA polymerase complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1592 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLR3F	POLR3C	Q9BUI4	979
POLR3F	POLR3G	O15318	972
POLR3F	POLR3H	Q9Y535	901
POLR3F	POLR3D	P05423	887
POLR3F	POLR3B	Q9NW08	874
POLR3F	POLR3E	Q9NVU0	874
POLR3F	POLR3A	O14802	846
POLR3F	POLR3K	Q9Y2Y1	816
POLR3F	CRCP	O75575	796
POLR3F	POLR1D	P0DPB6	774
POLR3F	BDP1	A6H8Y1	714
POLR3F	MIEN1	Q9BRT3	704
POLR3F	POLR3GL	Q9BT43	699
POLR3F	POLR2H	P52434	667
POLR3F	BRF1	Q92994	667

IntAct

155 interactions, top by confidence:

A	B	Type	Score
POLR3GL	POLR3C	psi-mi:“MI:0914”(association)	0.930
POLR2E	POLR3A	psi-mi:“MI:0914”(association)	0.870
POLR2E	POLR3A	psi-mi:“MI:0915”(physical association)	0.870
POLR3F	POLR3GL	psi-mi:“MI:0915”(physical association)	0.820
POLR3G	POLR3C	psi-mi:“MI:0914”(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
H2AC4	PPM1G	psi-mi:“MI:0914”(association)	0.670
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

BioGRID (145): POLR3F (Affinity Capture-MS), POLR3F (Affinity Capture-MS), POLR3F (Affinity Capture-MS), POLR3D (Co-fractionation), POLR3F (Co-fractionation), POLR3F (Co-fractionation), POLR3F (Co-fractionation), POLR3F (Co-fractionation), POLR3F (Co-fractionation), POLR3F (Co-fractionation), POLR3F (Co-fractionation), POLR3F (Co-fractionation), POLR3F (Co-fractionation), POLR3F (Co-fractionation), POLR3G (Co-fractionation)

ESM2 similar proteins: A2XKU9, A3KMV5, A4FUZ6, A4IHJ3, A7RHL5, A7RWP6, A9NK39, B4YYA9, B5X8A5, O42130, O42131, O46374, P10871, P11498, P17248, P22314, P23489, P52873, Q02880, Q05920, Q1JQD4, Q29504, Q29RK2, Q2T9S3, Q3ZBN0, Q40073, Q498C5, Q498D9, Q558Y7, Q5U300, Q64399, Q64511, Q66KC4, Q6AVK1, Q6DI37, Q6P5L8, Q6PAY8, Q6TGV7, Q6V289, Q7X923

Diamond homologs: O94553, P32910, P91529, Q9H1D9, Q9VD25, Q2T9S3, Q921X6, Q86JM3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
POLR3F	“form complex”	“RNA Polymerase III”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 75 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	184.6×	1e-34
RNA Polymerase III Transcription Termination	16	144.4×	1e-31
RNA Polymerase III Transcription Initiation From Type 2 Promoter	18	138.4×	1e-34
RNA Polymerase III Transcription Initiation From Type 1 Promoter	18	133.5×	1e-34
RNA Polymerase III Transcription Initiation From Type 3 Promoter	18	133.5×	1e-34
RNA Polymerase III Transcription Initiation	18	109.9×	1e-32
RNA Polymerase III Transcription	18	106.8×	2e-32
RNA Polymerase III Abortive And Retractive Initiation	18	91.2×	8e-31

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase III	7	81.2×	6e-10
positive regulation of innate immune response	5	39.9×	2e-05
positive regulation of interferon-beta production	5	29.7×	7e-05
transcription by RNA polymerase II	8	8.6×	3e-04
defense response to virus	8	8.4×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	107
Likely benign	51
Benign	18

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1687027	NM_006466.4(POLR3F):c.271C>T (p.Gln91Ter)	Pathogenic

SpliceAI

1235 predictions. Top by Δscore:

Variant	Effect	Δscore
20:18467390:G:GT	donor_gain	1.0000
20:18469050:T:TA	donor_gain	1.0000
20:18472905:GCTGG:G	donor_gain	1.0000
20:18472907:TGGG:T	donor_loss	1.0000
20:18472908:GG:G	donor_gain	1.0000
20:18472909:GG:G	donor_gain	1.0000
20:18472909:GGTA:G	donor_loss	1.0000
20:18472910:G:GG	donor_gain	1.0000
20:18472911:T:A	donor_loss	1.0000
20:18473384:A:AG	acceptor_gain	1.0000
20:18473389:A:AG	acceptor_gain	1.0000
20:18473390:G:GA	acceptor_gain	1.0000
20:18473390:GT:G	acceptor_gain	1.0000
20:18473390:GTA:G	acceptor_gain	1.0000
20:18473390:GTAA:G	acceptor_gain	1.0000
20:18473390:GTAAA:G	acceptor_gain	1.0000
20:18475150:A:T	donor_gain	1.0000
20:18475153:G:GG	donor_gain	1.0000
20:18475170:GCTGT:G	donor_gain	1.0000
20:18475174:T:G	donor_gain	1.0000
20:18475185:GCA:G	donor_gain	1.0000
20:18475188:G:GG	donor_gain	1.0000
20:18480032:TCCTA:T	acceptor_loss	1.0000
20:18480033:CCTA:C	acceptor_loss	1.0000
20:18480034:CTA:C	acceptor_loss	1.0000
20:18480035:TA:T	acceptor_loss	1.0000
20:18480036:A:AC	acceptor_loss	1.0000
20:18480036:A:AG	acceptor_gain	1.0000
20:18480036:AG:A	acceptor_gain	1.0000
20:18480037:G:GG	acceptor_gain	1.0000

AlphaMissense

2103 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:18468976:G:A	G32E	1.000
20:18472881:T:G	Y74D	1.000
20:18473423:T:C	L94P	1.000
20:18473426:T:A	V95E	1.000
20:18473438:T:A	I99K	1.000
20:18473438:T:G	I99R	1.000
20:18473446:G:C	A102P	1.000
20:18473458:G:A	G106R	1.000
20:18473458:G:C	G106R	1.000
20:18475075:G:A	G106E	1.000
20:18475075:G:T	G106V	1.000
20:18475080:T:A	W108R	1.000
20:18475080:T:C	W108R	1.000
20:18475082:G:C	W108C	1.000
20:18475082:G:T	W108C	1.000
20:18475087:G:C	R110T	1.000
20:18475087:G:T	R110I	1.000
20:18475088:A:C	R110S	1.000
20:18475088:A:T	R110S	1.000
20:18475093:T:A	I112N	1.000
20:18475095:C:A	R113S	1.000
20:18475096:G:C	R113P	1.000
20:18475104:A:C	S116R	1.000
20:18475106:T:A	S116R	1.000
20:18475106:T:G	S116R	1.000
20:18475131:A:G	K125E	1.000
20:18475138:T:C	L127P	1.000
20:18475140:A:G	K128E	1.000
20:18475147:T:C	L130P	1.000
20:18475162:T:C	L135P	1.000

dbSNP variants (sampled 300 via entrez): RS1000063122 (20:18475564 A>G), RS1000081128 (20:18482189 A>G), RS1000576117 (20:18470121 C>T), RS1000617113 (20:18472660 G>C), RS1000788581 (20:18466219 A>G), RS1000866737 (20:18483207 G>A), RS1001032449 (20:18476712 A>G), RS1001579083 (20:18466811 A>G), RS1001686168 (20:18473683 G>A), RS1001746817 (20:18473902 A>C,G), RS1001853659 (20:18467057 G>GC), RS1001905999 (20:18466790 G>A,C), RS1002178962 (20:18467971 G>A), RS1003160761 (20:18478714 A>T), RS1003361230 (20:18471907 G>A)

Disease associations

OMIM: gene MIM:617455 | disease phenotypes: MIM:619872, MIM:224100, MIM:616858

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 101 (varicella zoster virus-specific)	Limited	Unknown

Mondo (3): immunodeficiency 101 (varicella zoster virus-specific) (MONDO:0030813), congenital dyserythropoietic anemia type 2 (MONDO:0009134), Cowden syndrome 7 (MONDO:0014802)

Orphanet (2): Cowden syndrome (Orphanet:201), Congenital dyserythropoietic anemia type II (Orphanet:98873)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0005318	Cerebral vasculitis
HP:0034319	CNS vasculitis with reactivation of varicella-zoster virus

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_62	Refractive error	2.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Cadmium Chloride	affects expression, decreases expression	2
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
chloroacetaldehyde	increases expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
cobaltous chloride	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
nickel sulfate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Cidofovir	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Benzene	increases expression	1
Cisplatin	decreases expression	1
Clodronic Acid	decreases expression	1
Doxorubicin	increases expression	1
Estradiol	increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Oxygen	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Valproic Acid	decreases methylation, increases expression	1
Cyclosporine	increases expression	1
Particulate Matter	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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