POLR3H
protein-codingRNA polymerase III subunit H, the group of RNA polymerase subunits
Gene summary
Enables DNA-directed RNA polymerase activity. Involved in termination of RNA polymerase III transcription and transcription initiation at RNA polymerase III promoter. Located in centrosome and nucleoplasm. Part of RNA polymerase III complex. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~18.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0005387
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0009299
Submitter: Orphanet
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to POLR3H variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001018050.4. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 5 | ||||
| missense | 36 | 36 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 38 | 5 | 0 | 43 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001018060.1 | 6 | MANE Select | |
| Ensembl | ENSP00000347345.4 | 6 | MANE Select | |
| RefSeq | NP_001018062.1 | 5 | Standard | |
| RefSeq | NP_001269813.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| polr3h | Danio rerio | Structure: hematopoietic multipotent progenitor cell Quality: decreased amount 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
- nucleobase-containing compound metabolic process
- transcription by RNA polymerase III
- transcription initiation from RNA polymerase III promoter
- innate immune response
- defense response to virus
Molecular Function
- RNA polymerase III activity
- DNA binding
- DNA-directed 5'-3' RNA polymerase activity
Cellular Component
- nucleoplasm
- RNA polymerase III complex
- centrosome
- cytosol
- intracellular membrane-bounded organelle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000355209
- Coding exons
- 6
- Length
- 18803
- Individuals with no LoFs
- 125730
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125748
- p
- 0.0000716
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.136 | 123 | 127 | 0.966 | 0.00000742 | 1340 |
| Missense (PolyPhen) | 47 | 41.695 | 1.1272 | 472 | ||
| Synonymous | -1.93 | 71 | 53.1 | 1.34 | 0.00000357 | 387 |
| Loss of Function | 1.50 | 5 | 10.2 | 0.492 | 4.31e-7 | 120 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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. 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 (By similarity). {ECO:0000250, ECO:0000269|PubMed:19609254, ECO:0000269|PubMed:19631370}.;
Recessive Scores
- pRec
- 0.122
Intolerance Scores
- LoFtool
- 0.122
- RVIS EVS
- -0.54
- RVIS percentile EVS
- 20.26
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.707
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |