POLR2L

RNA polymerase II, I and III subunit L, the group of RNA polymerase subunits

Basic information

Region (hg38): 11:837356-842529

Links

ENSG00000177700 ∙ NCBI:5441 ∙ OMIM:601189 ∙ HGNC:9199 ∙ Uniprot:P62875 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POLR2L gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POLR2L 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						0
missense			5			5
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	5	0	0

Variants in POLR2L

This is a list of pathogenic ClinVar variants found in the POLR2L region.

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

Position	Type	Phenotype	Significance	ClinVar
11-837363-G-A		Epidermolysis bullosa simplex 7, with nephropathy and deafness;RAPH BLOOD GROUP SYSTEM	Likely benign (Jan 05, 2024)
11-837364-T-G			Likely benign (Sep 11, 2023)
11-837378-C-T			Benign (Dec 29, 2019)
11-837436-A-C			Benign (Dec 29, 2019)
11-837444-C-T		Epidermolysis bullosa simplex 7, with nephropathy and deafness;RAPH BLOOD GROUP SYSTEM	Benign/Likely benign (Aug 04, 2023)
11-837446-T-C			Benign (Aug 30, 2023)
11-837465-C-T			Uncertain significance (Aug 31, 2022)
11-837477-C-T			Likely benign (Jan 19, 2023)
11-837480-C-T			Likely benign (Apr 01, 2022)
11-837483-C-T		CD151-related disorder	Likely benign (Nov 03, 2023)
11-837496-C-T		Epidermolysis bullosa simplex 7, with nephropathy and deafness	Conflicting classifications of pathogenicity (Aug 09, 2022)
11-837497-G-A			Uncertain significance (Jul 06, 2023)
11-837505-G-A			Uncertain significance (Sep 17, 2023)
11-837507-G-T		Inborn genetic diseases	Uncertain significance (Aug 04, 2021)
11-837514-C-T		Epidermolysis bullosa simplex 7, with nephropathy and deafness	Uncertain significance (Dec 14, 2023)
11-837515-G-A			Uncertain significance (Oct 13, 2022)
11-837524-A-C			Uncertain significance (Nov 07, 2023)
11-837528-C-T			Likely benign (May 27, 2022)
11-837534-C-T			Likely benign (Jul 11, 2022)
11-837536-G-A			Uncertain significance (Nov 01, 2022)
11-837544-C-T			Uncertain significance (Sep 23, 2022)
11-837549-C-T			Likely benign (Jan 22, 2024)
11-837564-G-A			Likely benign (Apr 12, 2022)
11-837564-G-C			Likely benign (Mar 09, 2023)
11-837565-G-C		Inborn genetic diseases	Uncertain significance (Dec 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POLR2L	protein_coding	protein_coding	ENST00000322028	2	5190

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000454	0.258	124999	0	6	125005	0.0000240

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0828	39	40.5	0.963	0.00000252	411
Missense in Polyphen		4	4.8504	0.82467		72
Synonymous	-2.33	30	17.6	1.71	9.38e-7	135
Loss of Function	-1.10	4	2.23	1.79	9.43e-8	28

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000104	0.0000928
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000466	0.0000462
European (Non-Finnish)	0.0000100	0.00000888
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and a small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2L/RBP10 is part of the core element with the central large cleft (By similarity). {ECO:0000250, ECO:0000269|PubMed:9852112}.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);Huntington,s disease - 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;FGFR2 alternative splicing;Signaling by FGFR2;B-WICH complex positively regulates rRNA expression;Positive epigenetic regulation of rRNA expression;DNA Repair;Disease;RNA Pol II CTD phosphorylation and interaction with CE during HIV infection;NoRC negatively regulates rRNA expression;Negative epigenetic regulation of rRNA expression;Signal Transduction;Formation of the HIV-1 Early Elongation Complex;Epigenetic regulation of gene expression;Gene expression (Transcription);Signaling by FGFR;Formation of HIV-1 elongation complex containing HIV-1 Tat;Tat-mediated elongation of the HIV-1 transcript;Abortive elongation of HIV-1 transcript in the absence of Tat;HIV Transcription Elongation;HIV elongation arrest and recovery;Formation of HIV elongation complex in the absence of HIV Tat;Pausing and recovery of HIV elongation;Generic Transcription Pathway;Tat-mediated HIV elongation arrest and recovery;Pausing and recovery of Tat-mediated HIV elongation;Transcription of the HIV genome;Late Phase of HIV Life Cycle;HIV Life Cycle;HIV Infection;RNA Polymerase II HIV Promoter Escape;RNA Polymerase II Pre-transcription Events;RNA Polymerase II Transcription Initiation;RNA Polymerase II Transcription Initiation And Promoter Clearance;RNA Pol II CTD phosphorylation and interaction with CE;Viral Messenger RNA Synthesis;Influenza Viral RNA Transcription and Replication;Formation of RNA Pol II elongation complex ;Influenza Life Cycle;RNA Polymerase I Promoter Clearance;Influenza Infection;HIV Transcription Initiation;RNA polymerase II transcribes snRNA genes;RNA Polymerase II Transcription;Metabolism of RNA;Infectious disease;Purine metabolism;RNA Polymerase I Transcription Termination;RNA Polymerase I Transcription;RNA Polymerase II Transcription Elongation;mRNA Splicing - Major Pathway;RNA Polymerase I Transcription Initiation;RNA Polymerase I Promoter Escape;Pyrimidine metabolism;RNA Polymerase II Promoter Escape;RNA Polymerase I Chain Elongation;RNA Polymerase III Transcription Termination;RNA Polymerase II Transcription Pre-Initiation And Promoter Opening;RNA Polymerase III Chain Elongation;TP53 Regulates Transcription of DNA Repair Genes;Signaling by Nuclear Receptors;Transcriptional Regulation by TP53;mRNA Capping;Formation of the Early Elongation Complex;Estrogen-dependent gene expression;Transcriptional regulation by small RNAs;TNFalpha;Signaling by Receptor Tyrosine Kinases;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;ESR-mediated signaling;RNA Polymerase III Transcription Initiation From Type 3 Promoter;RNA Polymerase III Transcription Initiation;RNA Polymerase III Transcription;Formation of TC-NER Pre-Incision Complex;mRNA Splicing - Minor Pathway;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA;Dual incision in TC-NER;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair;Gene Silencing by RNA (Consensus)

Recessive Scores

• pRec: 0.363

Intolerance Scores

• loftool: 0.164
• rvis_EVS: -0.05
• rvis_percentile_EVS: 49.39

Haploinsufficiency Scores

• pHI: 0.461
• hipred: Y
• hipred_score: 0.618
• ghis: 0.581

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.463

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Polr2l

Gene ontology

• Biological process: mRNA splicing, via spliceosome;transcription-coupled nucleotide-excision repair;regulation of transcription by RNA polymerase I;transcription initiation from RNA polymerase I promoter;termination of RNA polymerase I transcription;transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;transcription elongation from RNA polymerase II promoter;7-methylguanosine mRNA capping;transcription by RNA polymerase III;fibroblast growth factor receptor signaling pathway;RNA metabolic process;snRNA transcription by RNA polymerase II;positive regulation of gene expression, epigenetic;regulation of gene silencing by miRNA
• Cellular component: nucleus;nucleoplasm;RNA polymerase II, core complex;RNA polymerase III complex;RNA polymerase I complex;cytosol
• Molecular function: RNA polymerase I activity;RNA polymerase II activity;RNA polymerase III activity;DNA binding;DNA-directed 5'-3' RNA polymerase activity;protein binding;zinc ion binding