GeneBe

POLR3F

protein-coding

RNA polymerase III subunit F, the group of RNA polymerase subunits|MicroRNA protein coding host genes

Gene summary

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. [provided by RefSeq, Sep 2013]

MANE transcript

NM_006466.4

Inheritance

AD

ClinVar variants

P:1U:92B:27

Top phenotype

Immunodeficiency 101 (varicella zoster virus-specific)

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr20:18,466,878-18,484,648

External References & Databases

Ensembl (ENSG00000132664)NCBI Gene (10621)OMIM (617455)HGNC:15763GenCCUniProt (Q9H1D9)AlphaFoldClinVar (POLR3F)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~17.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

immunodeficiency 101 (varicella zoster virus-specific)LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0030813

Submitter: PanelApp Australia

immunodeficiency 101 (varicella zoster virus-specific)LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030813

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Immunodeficiency 101 (varicella zoster virus-specific)AD

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: The condition involves susceptibility to sequelae of varicella infection, and acycloviri has been described as beneficial

Refs: 30211253Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to POLR3F variants in ClinVar

4 Conditions Cataloged
not providedTotal: 155
not specifiedTotal: 31
Immunodeficiency 101 (varicella zoster virus-specific)Total: 2
POLR3F-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006466.4. 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.

EffectPLPVUSLBBSum
synonymous
8
clinvar
23
clinvar
1
clinvar
 32
missense
70
clinvar
1
clinvar
1
clinvar
 72
nonsense
1
clinvar
2
clinvar
 3
start loss
0
frameshift
9
clinvar
 9
splice donor/acceptor (+/-2bp)
3
clinvar
1
clinvar
 4
Total1092252120
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_006466.4RefSeqNP_006457.29MANE Select
ENST00000377603.5EnsemblENSP00000366828.49MANE Select
NM_001282526.2RefSeqNP_001269455.18Standard
NM_001410821.1RefSeqNP_001397750.18Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
polr3fDanio rerio

Structure: head

Quality: decreased size

abnormal

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
  • double-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
ENST00000377603
Coding exons
9
Length
17517
Individuals with no LoFs
125644
Homozygous LoFs
0
Heterozygous LoFs
103
Defined
125747
p
0.000410
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.651091690.6440.000008332085
Missense (PolyPhen)1943.0560.44128547
Synonymous1.114960.00.8170.00000300550
Loss of Function1.351218.20.6588.69e-7228

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000120.00012rare
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish0.00630.0054notable
East Asian0.000120.00011rare
Finnish0.000280.00028rare
European (Non-Finnish)0.000260.00025rare
South Asian0.0000650.000065rare
Other0.00120.0011notable

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 peripheric component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. May direct RNA Pol III binding to the TFIIIB-DNA complex. 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 double-stranded DNA (dsDNA) (PubMed:21358628). {ECO:0000269|PubMed:19609254, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:21358628}.;

Recessive Scores

pRec
0.117

Intolerance Scores

LoFtool
0.427
RVIS EVS
-0.27
RVIS percentile EVS
33.97

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.993

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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