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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Charcot-Marie-Tooth disease, demyelinating, type 1I; Leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dental; Endocrine; Neurologic	22036171; 22036172; 25339210; 33417887; 34666706

ClinVar

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

• not provided (12 variants)
• Hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism (7 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			9	58	3	70
missense	5	13	161	5	1	185
nonsense	2	5	1			8
start loss						0
frameshift	8	3				11
inframe indel		1	3			4
splice donor/acceptor (+/-2bp)	1	11			2	14
splice region		1	17	9	2	29
non coding			15	67	64	146
Total	16	33	189	130	70

Highest pathogenic variant AF is 0.0000329

Variants in POLR3B

This is a list of pathogenic ClinVar variants found in the POLR3B region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-106357774-A-G		Hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism	Benign (Jan 13, 2018)
12-106357785-C-T		Hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism	Benign (Apr 16, 2019)
12-106357800-G-A			Likely benign (Feb 28, 2019)
12-106357841-G-T		Hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism	Uncertain significance (Jan 13, 2018)
12-106357843-G-T		Hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism	Uncertain significance (Jan 13, 2018)
12-106357879-C-T		Hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism	Benign (Nov 01, 2024)
12-106357890-T-C			Uncertain significance (Jan 15, 2024)
12-106357893-C-T		POLR3B-related disorder	Likely benign (Jun 04, 2023)
12-106357902-T-C			Uncertain significance (Jan 12, 2023)
12-106357909-C-T			Likely benign (Jun 05, 2022)
12-106357915-T-C			Likely benign (Sep 27, 2020)
12-106357924-G-C			Uncertain significance (Sep 06, 2023)
12-106357931-G-T			Uncertain significance (Dec 07, 2023)
12-106357932-C-T			Uncertain significance (Dec 07, 2023)
12-106357934-C-G			Uncertain significance (Jul 09, 2024)
12-106357935-C-G			Uncertain significance (Sep 01, 2022)
12-106357947-T-C		Inborn genetic diseases	Uncertain significance (Jan 10, 2022)
12-106357949-G-C			Uncertain significance (Jan 22, 2024)
12-106357956-G-A			Uncertain significance (Oct 13, 2023)
12-106357964-C-T			Uncertain significance (Jun 14, 2022)
12-106358027-G-A			Benign (Jul 17, 2018)
12-106358097-C-T			Benign (Jul 17, 2018)
12-106358132-GAGTGA-G		Charcot-Marie-Tooth disease, demyelinating, IIA 1I;Leukoencephalopathy, ataxia, hypodontia, hypomyelination syndrome;Hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism	Benign (Oct 25, 2021)
12-106358187-G-A			Likely benign (Feb 28, 2019)
12-106363577-A-G			Likely benign (Nov 15, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POLR3B	protein_coding	protein_coding	ENST00000228347	28	152541

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.68e-23	0.845	125630	0	118	125748	0.000469

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.20	402	627	0.641	0.0000348	7453
Missense in Polyphen		95	231.85	0.40974		2636
Synonymous	0.802	206	221	0.931	0.0000125	2118
Loss of Function	2.46	47	69.0	0.681	0.00000430	784

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000829	0.000829
Ashkenazi Jewish	0.000994	0.000993
East Asian	0.000763	0.000761
Finnish	0.000142	0.000139
European (Non-Finnish)	0.000432	0.000431
Middle Eastern	0.000763	0.000761
South Asian	0.000588	0.000588
Other	0.000163	0.000163

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

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

Mouse Genome Informatics

• Gene name: Polr3b

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