POLR3C

protein-coding

RNA polymerase III subunit C, the group of RNA polymerase subunits

Gene summary

Enables single-stranded DNA binding activity. Involved in positive regulation of innate immune response; positive regulation of interferon-beta production; and transcription by RNA polymerase III. Located in nucleoplasm. Part of RNA polymerase III complex. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_006468.8

Inheritance

ClinVar variants

U:78B:14

Top phenotype

POLR3C-related disorder

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr1:145,824,053-145,844,402

External References & Databases

Ensembl (ENSG00000186141)

Transcript & Mutation Effects

hg38 • Region Span ~20.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

varicella zoster infectionMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0005608

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to POLR3C variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 74

POLR3C-related disorderTotal: 11

not providedTotal: 1

Decreased total neutrophil countTotal: 1

Decreased total lymphocyte countTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006468.8. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	6 clinvar		7
missense			67 clinvar	7 clinvar		74
nonsense						0
start loss						0
frameshift			5 clinvar	1 clinvar		6
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	78	14	0	92

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006468.8	RefSeq	NP_006459.3	14	MANE Select
ENST00000334163.4	Ensembl	ENSP00000334564.3	14	MANE Select
NM_001303456.1	RefSeq	NP_001290385.1	15	Standard
ENST00000369294.5	Ensembl	ENSP00000358300.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pyrimidine metabolism - Homo sapiens (human)
Cytosolic DNA-sensing pathway - Homo sapiens (human)
RNA polymerase - Homo sapiens (human)
Purine metabolism - Homo sapiens (human)
Epstein-Barr virus infection - Homo sapiens (human)

Biological Process

regulation of transcription by RNA polymerase III
transcription by RNA polymerase III
positive regulation of interferon-beta production
innate immune response
positive regulation of innate immune response

Molecular Function

RNA polymerase III activity
single-stranded DNA binding
DNA-directed 5'-3' RNA polymerase activity
protein binding

Cellular Component

nucleoplasm
RNA polymerase III complex
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000334163
Coding exons: 14
Length: 18421
Individuals with no LoFs: 125380
Homozygous LoFs: 0
Heterozygous LoFs: 368
Defined: 125748
p: 0.00146

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.02	247	296	0.833	0.0000155	3483
Missense (PolyPhen)		64	80.104	0.79896		965
Synonymous	-1.30	125	108	1.16	0.00000552	1041
Loss of Function	1.43	22	30.5	0.721	0.00000172	356

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0010	0.0010	notable
Latino/Admixed American	0.0014	0.0014	notable
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00065	0.00065	rare
Finnish	0.00042	0.00042	rare
European (Non-Finnish)	0.0023	0.0023	notable
South Asian	0.00043	0.00042	rare
Other	0.0013	0.0013	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific core component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. May direct with other members of the subcomplex RNA Pol III binding to the TFIIIB- DNA complex via the interactions between TFIIIB and POLR3F. May be involved either in the recruitment and stabilization of the subcomplex within RNA polymerase III, or in stimulating catalytic functions of other subunits during initiation. Plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as 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 (PubMed:21358628). {ECO:0000269|PubMed:19609254, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:21358628}.;

Recessive Scores

pRec: 0.115

Intolerance Scores

LoFtool: 0.857
RVIS EVS: 0.58
RVIS percentile EVS: 82.17

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium