GeneBe

POLR3B

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

Basic information

Region (hg38): 12:106357748-106510198

Links

ENSG00000013503 ∙ NCBI:55703 ∙ OMIM:614366 ∙ HGNC:30348 ∙ Uniprot:Q9NW08 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism (Definitive), mode of inheritance: AR
  • hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism (Strong), mode of inheritance: AR
  • endosteal sclerosis-cerebellar hypoplasia syndrome (Supportive), mode of inheritance: AR
  • hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome (Supportive), mode of inheritance: AR
  • hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism (Definitive), mode of inheritance: AR
  • Charcot-Marie-Tooth disease, demyelinating, IIA 1I (Strong), mode of inheritance: AD
  • neurodevelopmental disorder (Strong), mode of inheritance: AD
  • neurodevelopmental disorder (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Charcot-Marie-Tooth disease, demyelinating, type 1I; Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadismAD/ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingDental; Endocrine; Neurologic22036171; 22036172; 25339210; 33417887; 34666706

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POLR3B gene.

  • not_provided (429 variants)
  • Hypomyelinating_leukodystrophy_8_with_or_without_oligodontia_and-or_hypogonadotropic_hypogonadism (145 variants)
  • Inborn_genetic_diseases (87 variants)
  • Charcot-Marie-Tooth_disease,_demyelinating,_IIA_1I (30 variants)
  • POLR3B-related_disorder (21 variants)
  • not_specified (11 variants)
  • POLR-related_leukodystrophy (8 variants)
  • See_cases (7 variants)
  • Leukoencephalopathy,_ataxia,_hypodontia,_hypomyelination_syndrome (6 variants)
  • Hypogonadotropic_hypogonadism (4 variants)
  • Hypogonadotropic_hypogonadism_7_with_or_without_anosmia (3 variants)
  • Amenorrhea (3 variants)
  • Intellectual_disability (2 variants)
  • Leukodystrophy (1 variants)
  • VISS_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POLR3B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018082.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
13
clinvar
81
clinvar
1
clinvar
 96
missense
9
clinvar
32
clinvar
268
clinvar
6
clinvar
 315
nonsense
3
clinvar
5
clinvar
5
clinvar
 13
start loss
0
frameshift
8
clinvar
4
clinvar
4
clinvar
1
clinvar
 17
splice donor/acceptor (+/-2bp)
1
clinvar
17
clinvar
6
clinvar
1
clinvar
 25
Total 21 59 296 88 2

Highest pathogenic variant AF is 0.00087124

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
POLR3Bprotein_codingprotein_codingENST00000228347 28152541
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.68e-230.84512563001181257480.000469
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense3.204026270.6410.00003487453
Missense in Polyphen95231.850.409742636
Synonymous0.8022062210.9310.00001252118
Loss of Function2.464769.00.6810.00000430784

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0008290.000829
Ashkenazi Jewish0.0009940.000993
East Asian0.0007630.000761
Finnish0.0001420.000139
European (Non-Finnish)0.0004320.000431
Middle Eastern0.0007630.000761
South Asian0.0005880.000588
Other0.0001630.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Second largest core component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. Proposed to contribute to the polymerase catalytic activity and forms the polymerase active center together with the largest subunit. Pol III is composed of mobile elements and RPC2 is part of the core element with the central large cleft and probably a clamp element that moves to open and close the cleft (By similarity). 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. {ECO:0000250, ECO:0000269|PubMed:19609254, ECO:0000269|PubMed:19631370}.;
Disease
DISEASE: Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism (HLD8) [MIM:614381]: An autosomal recessive neurodegenerative disorder characterized by early childhood onset of cerebellar ataxia and mild intellectual disabilities associated with diffuse hypomyelination apparent on brain MRI. Variable features include oligodontia and/or hypogonadotropic hypogonadism. {ECO:0000269|PubMed:22036171, ECO:0000269|PubMed:22036172, ECO:0000269|PubMed:23355746}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
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);Pyrimidine metabolism;Eukaryotic Transcription Initiation;Gene expression (Transcription);Purine metabolism;Pyrimidine metabolism;RNA Polymerase III Transcription Termination;RNA Polymerase III Chain Elongation;RNA Polymerase III Abortive And Retractive Initiation;RNA Polymerase III Transcription Initiation From Type 1 Promoter;RNA Polymerase III Transcription Initiation From Type 2 Promoter;RNA Polymerase III Transcription Initiation From Type 3 Promoter;RNA Polymerase III Transcription Initiation;RNA Polymerase III Transcription (Consensus)

Recessive Scores

pRec
0.130

Intolerance Scores

loftool
0.956
rvis_EVS
-1.48
rvis_percentile_EVS
3.66

Haploinsufficiency Scores

pHI
0.584
hipred
Y
hipred_score
0.648
ghis
0.594

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
E
essential_gene_gene_trap
E
gene_indispensability_pred
E
gene_indispensability_score
0.813

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Polr3b
Phenotype

Zebrafish Information Network

Gene name
polr3b
Affected structure
exocrine cell
Phenotype tag
abnormal
Phenotype quality
undifferentiated

Gene ontology

Biological process
transcription by RNA polymerase III;positive regulation of interferon-beta production;innate immune response;positive regulation of innate immune response;defense response to virus
Cellular component
nucleoplasm;RNA polymerase III complex;cytosol
Molecular function
RNA polymerase III activity;DNA binding;DNA-directed 5'-3' RNA polymerase activity;ribonucleoside binding;metal ion binding