POLR1B

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

Basic information

Region (hg38): 2:112541915-112579818

Links

ENSG00000125630 ∙ NCBI:84172 ∙ OMIM:602000 ∙ HGNC:20454 ∙ Uniprot:Q9H9Y6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Treacher-Collins syndrome (Supportive), mode of inheritance: AD
• Treacher Collins syndrome 4 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Treacher-Collins syndrome 4	AD	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial	31649276

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POLR1B gene.

• Treacher Collins syndrome (1 variants)
• Treacher Collins syndrome 4 (1 variants)
• POLR1B-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POLR1B 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					3	3
missense	1		49	6	2	58
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					3	3
non coding				1	32	33
Total	1	0	51	7	37

Variants in POLR1B

This is a list of pathogenic ClinVar variants found in the POLR1B region.

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

Position	Type	Phenotype	Significance	ClinVar
2-112542416-G-A		POLR1B-related disorder	Likely benign (Apr 26, 2023)
2-112542424-TTCCGGCGTGTACCGAGAGACTGGCG-T			Benign (Mar 22, 2022)
2-112542550-T-C		Treacher Collins syndrome 4	Uncertain significance (Jul 22, 2022)
2-112542642-G-A			Uncertain significance (Jun 01, 2022)
2-112542706-C-G			Benign (May 14, 2021)
2-112542753-G-A			Benign (May 14, 2021)
2-112542817-A-C			Benign (May 14, 2021)
2-112547049-G-T		not specified	Uncertain significance (Aug 12, 2021)
2-112547114-A-C		not specified	Uncertain significance (Dec 15, 2023)
2-112547135-G-A		not specified	Uncertain significance (Aug 01, 2022)
2-112547479-G-C			Uncertain significance (Jan 04, 2024)
2-112547506-A-C		not specified	Uncertain significance (Sep 26, 2023)
2-112547533-C-A		not specified	Uncertain significance (Feb 13, 2023)
2-112547562-G-A		not specified	Uncertain significance (May 30, 2024)
2-112547565-G-T		Treacher Collins syndrome 4	Likely pathogenic (Jun 05, 2024)
2-112547573-G-C			Benign (May 04, 2021)
2-112547575-C-T			Benign (May 19, 2021)
2-112547781-G-A			Benign (May 15, 2021)
2-112549250-A-G			Benign (May 14, 2021)
2-112549352-T-C		not specified	Uncertain significance (Aug 19, 2023)
2-112549446-CT-C			Benign (May 14, 2021)
2-112549446-C-CT			Benign (Jun 02, 2021)
2-112549499-CT-C			Benign (May 17, 2021)
2-112549504-T-C			Benign (Jun 01, 2021)
2-112549538-C-T			Benign (May 14, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POLR1B	protein_coding	protein_coding	ENST00000263331	15	35144

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000542	125729	0	17	125746	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.97	423	634	0.668	0.0000352	7524
Missense in Polyphen		79	244.65	0.32291		2782
Synonymous	-0.353	236	229	1.03	0.0000125	2195
Loss of Function	5.63	6	48.1	0.125	0.00000274	579

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000276	0.000275
Ashkenazi Jewish	0.00	0.00
East Asian	0.000111	0.000109
Finnish	0.000140	0.000139
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.000111	0.000109
South Asian	0.00	0.00
Other	0.000176	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 I which synthesizes ribosomal RNA precursors. Proposed to contribute to the polymerase catalytic activity and forms the polymerase active center together with the largest subunit. Pol I is composed of mobile elements and RPA2 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). {ECO:0000250}.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);RNA polymerase - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Pyrimidine metabolism;Eukaryotic Transcription Initiation;B-WICH complex positively regulates rRNA expression;Positive epigenetic regulation of rRNA expression;NoRC negatively regulates rRNA expression;Negative epigenetic regulation of rRNA expression;Epigenetic regulation of gene expression;Gene expression (Transcription);tumor suppressor arf inhibits ribosomal biogenesis;RNA Polymerase I Promoter Clearance;Purine metabolism;RNA Polymerase I Transcription Termination;RNA Polymerase I Transcription;RNA Polymerase I Transcription Initiation;RNA Polymerase I Promoter Escape;Pyrimidine metabolism;RNA Polymerase I Chain Elongation;TNFalpha (Consensus)

Recessive Scores

• pRec: 0.200

Intolerance Scores

• loftool: 0.566
• rvis_EVS: -0.75
• rvis_percentile_EVS: 13.75

Haploinsufficiency Scores

• pHI: 0.407
• hipred: Y
• hipred_score: 0.756
• ghis: 0.651

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.860

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Polr1b
• Phenotype: embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cellular phenotype

Gene ontology

• Biological process: transcription initiation from RNA polymerase I promoter;termination of RNA polymerase I transcription;embryo implantation;rRNA transcription;nucleologenesis;positive regulation of gene expression, epigenetic
• Cellular component: nucleoplasm;nucleolus;RNA polymerase I complex;cytosol
• Molecular function: RNA polymerase I activity;DNA binding;DNA-directed 5'-3' RNA polymerase activity;protein binding;ribonucleoside binding;metal ion binding