POLR3C

Summary

POLR3C (RNA polymerase III subunit C, HGNC:30076) is a protein-coding gene on chromosome 1q21.1, encoding DNA-directed RNA polymerase III subunit RPC3 (Q9BUI4). 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 96.2% of cancer cell lines).

Enables single-stranded DNA binding activity. Involved in positive regulation of innate immune response and positive regulation of interferon-beta production. Located in nucleoplasm. Part of RNA polymerase III complex.

Source: NCBI Gene 10623 — RefSeq curated summary.

At a glance

• Gene–disease (curated): varicella zoster infection (Moderate, GenCC)
• Clinical variants (ClinVar): 96 total — 2 pathogenic
• Phenotypes (HPO): 2
• Cancer dependency (DepMap): dependent in 96.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_006468

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30076
Approved symbol	POLR3C
Name	RNA polymerase III subunit C
Location	1q21.1
Locus type	gene with protein product
Status	Approved
Aliases	RPC62, RPC3, C82
Ensembl gene	ENSG00000186141
Ensembl biotype	protein_coding
OMIM	617454
Entrez	10623

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 14 retained_intron, 13 protein_coding, 4 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000334163, ENST00000369294, ENST00000466003, ENST00000471254, ENST00000479819, ENST00000489436, ENST00000698751, ENST00000698752, ENST00000698753, ENST00000698754, ENST00000698755, ENST00000698756, ENST00000698757, ENST00000698758, ENST00000698759, ENST00000698760, ENST00000698761, ENST00000698762, ENST00000698763, ENST00000698764, ENST00000698765, ENST00000698766, ENST00000698767, ENST00000698768, ENST00000698769, ENST00000698770, ENST00000698771, ENST00000891279, ENST00000891280, ENST00000891281, ENST00000891282, ENST00000970323, ENST00000970324, ENST00000970325, ENST00000970326

RefSeq mRNA: 2 — MANE Select: NM_006468 NM_001303456, NM_006468

CCDS: CCDS72864

Canonical transcript exons

ENST00000334163 — 15 exons

Exon	Start	End
ENSE00001339889	145842339	145844402
ENSE00001339957	145824200	145824369
ENSE00001885746	145826454	145826709
ENSE00001954716	145833260	145833364
ENSE00003551079	145826820	145827005
ENSE00003558052	145825757	145825923
ENSE00003687304	145828749	145828837
ENSE00003974644	145840922	145841071
ENSE00003974657	145839890	145839991
ENSE00003974662	145838056	145838206
ENSE00003974666	145840116	145840165
ENSE00003974670	145837536	145837596
ENSE00003974675	145833490	145833582
ENSE00003974685	145836815	145836866
ENSE00003974688	145836494	145836574

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 91.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.2795 / max 249.6083, expressed in 1818 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4950	27.4539	1814
4949	1.3943	886
201671	0.7263	440
4948	0.6832	389
4951	0.0218	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.84	gold quality
calcaneal tendon	UBERON:0003701	90.10	gold quality
stromal cell of endometrium	CL:0002255	88.95	gold quality
monocyte	CL:0000576	88.54	gold quality
left testis	UBERON:0004533	88.54	gold quality
right testis	UBERON:0004534	88.20	gold quality
mononuclear cell	CL:0000842	88.19	gold quality
leukocyte	CL:0000738	88.18	gold quality
endocervix	UBERON:0000458	88.08	gold quality
testis	UBERON:0000473	87.78	gold quality
granulocyte	CL:0000094	87.73	gold quality
gall bladder	UBERON:0002110	87.72	gold quality
right ovary	UBERON:0002118	87.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.22	gold quality
left ovary	UBERON:0002119	87.19	gold quality
tibial artery	UBERON:0007610	87.07	gold quality
popliteal artery	UBERON:0002250	87.06	gold quality
ganglionic eminence	UBERON:0004023	87.00	gold quality
ectocervix	UBERON:0012249	86.95	gold quality
skin of leg	UBERON:0001511	86.83	gold quality
mucosa of stomach	UBERON:0001199	86.76	gold quality
body of uterus	UBERON:0009853	86.67	gold quality
tibial nerve	UBERON:0001323	86.61	gold quality
descending thoracic aorta	UBERON:0002345	86.59	gold quality
right lung	UBERON:0002167	86.55	gold quality
aorta	UBERON:0000947	86.29	gold quality
body of pancreas	UBERON:0001150	86.24	gold quality
right coronary artery	UBERON:0001625	86.17	gold quality
minor salivary gland	UBERON:0001830	86.05	gold quality
left coronary artery	UBERON:0001626	85.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

79 targeting POLR3C, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-889-5P	99.41	68.75	1025

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.2% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 4)

• The study reports the crystal structure of RPC62. (PMID:21358628)
• monogenic or digenic POLR3A and POLR3C deficiencies confer increased susceptibility to severe VZV disease in otherwise healthy children, providing evidence for an essential role of a DNA sensor in human immunity (PMID:28783042)
• the eWH domain of hTFIIEalpha can replace the first eWH (eWH1) domain of hRPC62 in ATPase and DNA unwinding assays. Our results identify intrinsic enzymatic activities in hRPC62 and hTFIIEalpha. (PMID:31529052)
• From Rare Copy Number Variants to Biological Processes in ADHD. (PMID:32600152)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	polr3c	ENSDARG00000057562
mus_musculus	Polr3c	ENSMUSG00000028099
rattus_norvegicus	Polr3c	ENSRNOG00000033560
drosophila_melanogaster	Polr3C	FBGN0038057
caenorhabditis_elegans	let-611	WBGENE00016750

Protein

Protein identifiers

DNA-directed RNA polymerase III subunit RPC3 — Q9BUI4 (reviewed: Q9BUI4)

Alternative names: DNA-directed RNA polymerase III subunit C, RNA polymerase III 62 kDa subunit

All UniProt accessions (6): A0A8V8TM54, A0A8V8TM82, A0A8V8TMN9, A0A8V8TNN2, E9PHH9, Q9BUI4

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, 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. 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. Preferentially binds single-stranded DNA (ssDNA) in a sequence-independent manner.

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 POLR3G/RPC7 and POLR3GL. Directly interacts with POLR3F/RPC6. Interacts with GTF3C4. As part of the RNA polymerase III complex, interacts with PKP2.

Subcellular location. Nucleus.

Miscellaneous. Antibodies against POLR3C have been found in the sera of patients with systemic sclerosis (SSc).

Similarity. Belongs to the eukaryotic RPC3/POLR3C RNA polymerase subunit family.

RefSeq proteins (2): NP_001290385, NP_006459* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008806	RNA_pol_III_Rpc82_C	Domain
IPR013197	RNA_pol_III_RPC82-rel_HTH	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR039748	RPC3	Family
IPR055207	POLR3C_WHD	Domain

Pfam: PF05645, PF08221, PF20912, PF22536

UniProt features (67 total): helix 22, strand 18, sequence conflict 10, mutagenesis site 7, turn 4, region of interest 2, chain 1, compositionally biased region 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

32 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2XUB	X-RAY DIFFRACTION	2.8
7AE1	ELECTRON MICROSCOPY	2.8
9K39	ELECTRON MICROSCOPY	2.8
7D58	ELECTRON MICROSCOPY	2.9
9K36	ELECTRON MICROSCOPY	2.9
2XV4	X-RAY DIFFRACTION	2.95
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

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BUI4-F1	89.27	0.74

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 (1): 194

Mutagenesis-validated functional residues (7):

Position	Phenotype
389	strongly decreased ssdna-binding. no effect on interaction with polr3f, polr3g, nor with polr3gl.
445–449	strongly decreased ssdna-binding. no effect on interaction with polr3f, polr3g, nor with polr3gl.
466–470	mild decrease in ssdna-binding. no effect on interaction with polr3f, polr3g, nor with polr3gl.
51–52	strongly decreased ssdna-binding. no effect on interaction with polr3f, polr3g, nor with polr3gl.
312	loss of interaction with polr3g and polr3gl. no effect on interaction with polr3f.
357	strongly decreased ssdna-binding. no effect on interaction with polr3f, polr3g, nor with polr3gl.
364–367	strongly decreased ssdna-binding. no effect on interaction with polr3f, polr3g, nor with polr3gl.

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: 209 (showing top): REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_INITIATION_FROM_TYPE_3_PROMOTER, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, 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, DITTMER_PTHLH_TARGETS_UP, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, MORF_PSMC2, KEGG_CYTOSOLIC_DNA_SENSING_PATHWAY, PUJANA_CHEK2_PCC_NETWORK, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE

GO Biological Process (7): DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase III (GO:0006359), 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 (4): single-stranded DNA binding (GO:0003697), DNA-directed RNA polymerase activity (GO:0003899), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (5): nucleoplasm (GO:0005654), RNA polymerase III complex (GO:0005666), cytosol (GO:0005829), DNA-directed RNA polymerase complex (GO:0000428), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
RNA Polymerase III Transcription	4
RNA Polymerase III Transcription Initiation	3
Innate Immune System	1
Immune System	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA biosynthetic process	2
cellular anatomical structure	2
gene expression	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase III	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
5’-3’ RNA polymerase activity	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

Protein interactions and networks

STRING

2555 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLR3C	POLR3G	O15318	992
POLR3C	POLR3F	Q9H1D9	979
POLR3C	POLR3D	P05423	893
POLR3C	POLR3A	O14802	862
POLR3C	POLR3GL	Q9BT43	855
POLR3C	POLR3E	Q9NVU0	846
POLR3C	POLR3H	Q9Y535	818
POLR3C	POLR3K	Q9Y2Y1	813
POLR3C	POLR3B	Q9NW08	807
POLR3C	POLR1D	P0DPB6	776
POLR3C	CRCP	O75575	775
POLR3C	BDP1	A6H8Y1	748
POLR3C	POLR2F	P41584	743
POLR3C	POLR2E	P19388	718
POLR3C	POLR2H	P52434	707

IntAct

239 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
POLR2E	POLR3A	psi-mi:“MI:0914”(association)	0.870
POLR2E	POLR3A	psi-mi:“MI:0915”(physical association)	0.870
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
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
KPNA1	POLR3C	psi-mi:“MI:0915”(physical association)	0.740
POLR3GL	POLR3A	psi-mi:“MI:0914”(association)	0.730
POLR3C	TRIM27	psi-mi:“MI:0915”(physical association)	0.720
TRIM27	POLR3C	psi-mi:“MI:0915”(physical association)	0.720
POLR3D	POLR3A	psi-mi:“MI:0914”(association)	0.640
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
KIAA0408	POLR3C	psi-mi:“MI:0915”(physical association)	0.600
POLR3C	KIAA0408	psi-mi:“MI:0915”(physical association)	0.600
POLR3C	TNR	psi-mi:“MI:0915”(physical association)	0.560
POLR3C	ROCK1	psi-mi:“MI:0915”(physical association)	0.560
POLR3C	PNMA5	psi-mi:“MI:0915”(physical association)	0.560
ROPN1	POLR3C	psi-mi:“MI:0915”(physical association)	0.560
ROCK1	POLR3C	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (191): POLR3C (Two-hybrid), POLR3C (Two-hybrid), POLR3C (Two-hybrid), ROPN1 (Two-hybrid), CEP63 (Two-hybrid), PNMA5 (Two-hybrid), POLR3C (Affinity Capture-MS), POLR3C (Affinity Capture-MS), CRCP (Co-fractionation), POLR1C (Co-fractionation), POLR1D (Co-fractionation), POLR2H (Co-fractionation), POLR2L (Co-fractionation), POLR3B (Co-fractionation), POLR3C (Co-fractionation)

ESM2 similar proteins: A1C9R2, A1CKN7, A1CQH8, A1CZJ5, A1D6T6, A1D8E4, A2Q8I1, A2QPL8, A2R9P6, A4RK04, A4RM69, A5AAA4, A6S936, B0XQ54, B0XXL3, G0S8F1, P0CN50, P0CN51, P0CO78, P0CO79, P54898, Q0CA25, Q0CNR3, Q0CUP6, Q0TYW1, Q0U2G5, Q1DTI6, Q1DXU0, Q1E170, Q2H6G4, Q2H991, Q2TBL4, Q2UKS9, Q4IMN9, Q4INS6, Q4WJX0, Q4WTH1, Q4WTQ4, Q4WY08, Q5AS80

Diamond homologs: A6R9K6, Q2TBL4, Q5A246, Q5ATV8, Q5XIL3, Q6C2E2, Q7ZUX1, Q9BUI4, Q9D483, Q9C106

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
POLR3C	“form complex”	“RNA Polymerase III”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 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	15	173.0×	2e-31
RNA Polymerase III Transcription Termination	15	135.4×	7e-29
RNA Polymerase III Transcription Initiation From Type 2 Promoter	17	130.7×	8e-32
RNA Polymerase III Transcription Initiation From Type 1 Promoter	17	126.1×	8e-32
RNA Polymerase III Transcription Initiation From Type 3 Promoter	17	126.1×	8e-32
RNA Polymerase III Transcription Initiation	17	103.8×	5e-30
RNA Polymerase III Transcription	17	100.8×	9e-30
RNA Polymerase III Abortive And Retractive Initiation	17	86.1×	2e-28

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase III	7	73.5×	2e-09
positive regulation of interferon-beta production	5	26.8×	2e-04
protein import into nucleus	5	9.9×	6e-03
transcription by RNA polymerase II	8	7.7×	7e-04
defense response to virus	8	7.6×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	67
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1807758	GRCh37/hg19 1q21.1(chr1:145083851-145986573)x1	Pathogenic
33116	GRCh38/hg38 1q21.1-21.2(chr1:145215697-149076087)x1	Pathogenic

SpliceAI

1474 predictions. Top by Δscore:

Variant	Effect	Δscore
1:145824448:T:TA	donor_gain	1.0000
1:145825754:C:CC	acceptor_gain	1.0000
1:145825812:A:T	acceptor_gain	1.0000
1:145825816:T:C	acceptor_gain	1.0000
1:145825816:T:TC	acceptor_gain	1.0000
1:145826440:A:AC	acceptor_gain	1.0000
1:145826440:A:C	acceptor_gain	1.0000
1:145826441:C:CT	acceptor_gain	1.0000
1:145826451:C:CC	acceptor_gain	1.0000
1:145826451:CT:C	acceptor_loss	1.0000
1:145826452:CCT:C	acceptor_loss	1.0000
1:145826453:ACC:A	acceptor_loss	1.0000
1:145826454:CAC:C	acceptor_gain	1.0000
1:145826708:C:A	donor_loss	1.0000
1:145826708:C:CC	donor_gain	1.0000
1:145826708:CC:C	donor_gain	1.0000
1:145826708:CCCT:C	donor_gain	1.0000
1:145826708:CCCTC:C	donor_gain	1.0000
1:145826709:A:AC	donor_gain	1.0000
1:145826709:A:AT	donor_loss	1.0000
1:145826709:AC:A	donor_gain	1.0000
1:145826709:ACCCT:A	donor_gain	1.0000
1:145826711:TGAC:T	donor_loss	1.0000
1:145826712:C:CC	donor_gain	1.0000
1:145826713:A:AC	donor_gain	1.0000
1:145826808:A:T	acceptor_gain	1.0000
1:145826809:C:CT	acceptor_gain	1.0000
1:145826813:A:C	acceptor_gain	1.0000
1:145826815:G:C	acceptor_gain	1.0000
1:145826815:G:GC	acceptor_gain	1.0000

AlphaMissense

3503 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:145833284:T:A	W235R	1.000
1:145833284:T:C	W235R	1.000
1:145826620:T:C	L105P	0.999
1:145826689:G:C	R128P	0.999
1:145833285:G:C	W235S	0.999
1:145833286:G:C	W235C	0.999
1:145833286:G:T	W235C	0.999
1:145833321:G:C	R247P	0.999
1:145840953:G:C	A469P	0.999
1:145826467:T:C	L54P	0.998
1:145826529:T:G	Y75D	0.998
1:145826593:A:T	K96I	0.998
1:145826635:T:C	L110P	0.998
1:145826647:G:T	G114V	0.998
1:145826682:G:C	A126P	0.998
1:145826868:T:C	L151P	0.998
1:145826886:T:A	V157E	0.998
1:145833518:T:C	L271P	0.998
1:145836552:T:C	L312P	0.998
1:145838156:G:C	A391P	0.998
1:145839901:A:C	K411N	0.998
1:145839901:A:T	K411N	0.998
1:145839915:C:A	A416D	0.998
1:145839924:G:C	R419T	0.998
1:145839924:G:T	R419M	0.998
1:145839925:G:C	R419S	0.998
1:145839925:G:T	R419S	0.998
1:145840946:G:C	R466S	0.998
1:145840946:G:T	R466S	0.998
1:145840962:G:C	A472P	0.998

dbSNP variants (sampled 300 via entrez): RS1000073992 (1:145823949 T>C,G), RS1000137256 (1:145831000 G>A), RS1000431646 (1:145829965 G>A), RS1000777793 (1:145842081 C>T), RS1001204013 (1:145841523 C>G,T), RS1001221017 (1:145834858 G>A,C,T), RS1001415908 (1:145835038 C>T), RS1002848017 (1:145840254 G>A,C), RS1002879027 (1:145839800 G>A), RS1003002297 (1:145834225 A>T), RS1003090627 (1:145827691 G>A), RS1003211267 (1:145838734 C>G), RS1003413698 (1:145832374 A>C,G), RS1003484585 (1:145833953 A>T), RS1003749530 (1:145832730 T>C,G)

Disease associations

OMIM: gene MIM:617454 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
varicella zoster infection	Moderate	Autosomal dominant

Mondo (3): neutropenia (MONDO:0001475), lymphopenia (MONDO:0003783), varicella zoster infection (MONDO:0005608)

Orphanet (0):

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0001875	Decreased total neutrophil count
HP:0001888	Decreased total lymphocyte count

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008231	Lymphopenia	C15.378.243.750.605; C15.378.553.546.605; C20.673.627
D009503	Neutropenia	C15.378.243.750.184.564; C15.378.553.546.184.564

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	5
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cyclosporine	increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
monomethylarsonous acid	increases expression	1
K 7174	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Atrazine	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Phenobarbital	affects expression	1
Quercetin	increases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
T-2 Toxin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Tunicamycin	increases expression	1
Valproic Acid	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01682109	PHASE4	COMPLETED	Palatability Testing of a New Paediatric Formulation of Valacyclovir
NCT04403139	PHASE4	ACTIVE_NOT_RECRUITING	VZV-specific Tissue Resident Memory T-cells After Shingrix Vaccination
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00125723	PHASE4	COMPLETED	FIRST - Study of Pegfilgrastim Administered in the First and Subsequent Cycles of Myelosuppressive Chemotherapy
NCT00194857	PHASE4	TERMINATED	Treatment of Anemia and Neutropenia in HIV/HCV Coinfected Patients Treated With Pegylated Interferon and Ribavirin
NCT00257790	PHASE4	COMPLETED	The Tobramycin Study
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00686543	PHASE4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01086878	PHASE4	COMPLETED	Safety of Cotrimoxazole in HIV- and HAART-exposed Infants
NCT01114165	PHASE4	COMPLETED	Value of the LightCycler® SeptiFast Test MGRADE for the Pathogen Detection in Neutropenic Hematological Patients
NCT01135589	PHASE4	UNKNOWN	Micafungin Prevention Study for Fungal Disease in Child Receiving Allogenic Hematopoietic Stem Cell Transplantation
NCT01571518	PHASE4	UNKNOWN	Prevention of Neutropenia After Using G-CSF With TAC Chemotherapy
NCT02621905	PHASE4	COMPLETED	Steady-State Comparative Bioavailability Study in Prophylaxis Patients of Lozanoc® 50 mg With Sporanox® 100 mg
NCT02967341	PHASE4	UNKNOWN	Blood Draw Validation for Ciprofloxacin Pharmacokinetic Research in Pediatric Cancer Patients
NCT04009941	PHASE4	COMPLETED	Efficacy and Safety of 4.5mg PEG-rhG-CSF Per Cycle in Preventing Neutropenia After Intensive Chemotherapy for Breast Cancer
NCT04904614	PHASE4	COMPLETED	Letermovir Use in Heart Transplant Recipients
NCT05626530	PHASE4	RECRUITING	Letermovir for Secondary Prophylaxis in Solid Organ Transplant Recipients
NCT06145321	PHASE4	ACTIVE_NOT_RECRUITING	Continuous Versus Bolus Administration of G-CSF in Children With Cancer
NCT00001338	PHASE3	COMPLETED	A Prospective, Randomized, Phase III Trial of FLAC (5-Fluorouracil, Leucovorin, Adriamycin, Cytoxan) Chemotherapy With GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor) Versus PIXY 321 in Advanced Breast Cancer
NCT00001646	PHASE3	COMPLETED	Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
NCT00002658	PHASE3	UNKNOWN	Combination Chemotherapy, Biological Therapy, and Bone Marrow Transplantation in Treating Patients With Acute Myeloid Leukemia
NCT00002719	PHASE3	COMPLETED	Combination Chemotherapy With or Without G-CSF in Treating Older Patients With Acute Myeloid Leukemia
NCT00003739	PHASE3	COMPLETED	Antibiotic Therapy With or Without G-CSF in Treating Children With Neutropenia and Fever Caused by Chemotherapy
NCT00020865	PHASE3	UNKNOWN	Levofloxacin Compared With Cefepime in Treating Cancer Patients With Fever and Neutropenia
NCT00035594	PHASE3	COMPLETED	Pegfilgrastim as Support to Advanced Breast Cancer Patients Receiving Chemotherapy
NCT00044486	PHASE3	COMPLETED	Prophylaxis Trial of Posaconazole Versus Standard Azole Therapy for Neutropenic Patients (Study P01899)
NCT00107081	PHASE3	TERMINATED	Low-risk Fever and Neutropenia in Children With Cancer: Safety and Efficacy of Oral Antibiotics in an Outpatient Setting
NCT00445497	PHASE3	UNKNOWN	Early Hospital Discharge or Standard Inpatient Care in Cancer Patients Receiving Antibiotics for Febrile Neutropenia
NCT00529282	PHASE3	TERMINATED	A Study of Ceftobiprole in Patients With Fever and Neutropenia.
NCT00627393	PHASE3	COMPLETED	Safety and Effectiveness of Granulocyte Transfusions in Resolving Infection in People With Neutropenia (The RING Study)
NCT00770172	PHASE3	COMPLETED	G-CSF in Preventing Neutropenia in Patients With Solid Tumors Who Are Receiving Chemotherapy
NCT00784368	PHASE3	COMPLETED	A Pharmacokinetic Study of JK1211(Itraconazole [Itrizole]) Oral Solution in Participants With Deep Mycosis and Those With Febrile Neutropenia Suspected of Fungal Infection
NCT00806351	PHASE3	TERMINATED	An Evaluation Of The Effectiveness And Safety Of Anidulafungin Compared To Caspofungin For The Treatment Of Serious Fungal Infection Due To Candida In Patients With A Dysfunctional Immune System
NCT00911170	PHASE3	COMPLETED	PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study
NCT01307579	PHASE3	COMPLETED	Caspofungin Versus Fluconazole in Preventing Invasive Fungal Infections (IFI) in Patients Undergoing Chemotherapy for Acute Myeloid Leukemia
NCT01371656	PHASE3	COMPLETED	Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation
NCT01560195	PHASE3	UNKNOWN	A Study of Pegylated rhG-CSF as Support to Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients Receiving Chemotherapy Receiving Chemotherapy
NCT01611051	PHASE3	COMPLETED	A Study Comparing Pegylated rhG-CSF and rhG-CSF as Support to Breast Cancer Patients Receiving Chemotherapy
NCT02238873	PHASE3	UNKNOWN	Pegfilgrastim on Day +3 Compared to Day +1 After Salvage Chemotherapy for Patients With Refractory or Relapsed Aggressive Lymphoma
NCT02414581	PHASE3	COMPLETED	Mouthwash With Chlorhexidine 0.12%/Ethyl Alcohol 7% Compared to Ethyl Alcohol 7%