POLR2A

RNA polymerase II subunit A, the group of RNA polymerase subunits

Basic information

Region (hg38): 17:7484366-7514616

Previous symbols: [ "POLR2" ]

Links

ENSG00000181222 ∙ NCBI:5430 ∙ OMIM:180660 ∙ HGNC:9187 ∙ Uniprot:P24928 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism, susceptibility to, 15 (Definitive), mode of inheritance: AD
• neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities (Moderate), mode of inheritance: AD
• neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities (Strong), mode of inheritance: AD
• neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities (Moderate), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POLR2A gene.

• Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POLR2A 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			2	42	12	56
missense		16	144	7		167
nonsense	1	4	5			10
start loss						0
frameshift		1	4		1	6
inframe indel		1	5	3		9
splice donor/acceptor (+/-2bp)			2			2
splice region			6	4	3	13
non coding				2	5	7
Total	1	22	162	54	18

Variants in POLR2A

This is a list of pathogenic ClinVar variants found in the POLR2A region.

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

Position	Type	Phenotype	Significance	ClinVar
17-7484770-C-G			Uncertain significance (Jun 14, 2024)
17-7484770-C-T			Likely benign (Jul 01, 2024)
17-7484784-C-T		Inborn genetic diseases	Uncertain significance (Jun 13, 2024)
17-7484820-A-G		Inborn genetic diseases	Uncertain significance (Oct 12, 2021)
17-7484824-A-C			Uncertain significance (Oct 01, 2022)
17-7484830-G-T			Uncertain significance (Jan 25, 2023)
17-7484833-C-G		Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities	Uncertain significance (Jun 07, 2022)
17-7484847-C-G		Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities	Uncertain significance (Apr 07, 2020)
17-7484847-C-T			Uncertain significance (Feb 28, 2023)
17-7484849-G-C		See cases	Uncertain significance (Jun 02, 2021)
17-7484853-A-T		not specified	Likely benign (May 08, 2020)
17-7495924-CCTTT-C		POLR2A-related disorder	Benign (Dec 05, 2019)
17-7495984-C-T		Inborn genetic diseases	Uncertain significance (Dec 17, 2023)
17-7495999-G-A		POLR2A-related disorder	Uncertain significance (Aug 25, 2023)
17-7496000-C-T		POLR2A-related disorder	Benign (Nov 20, 2019)
17-7496007-C-T			Uncertain significance (Apr 04, 2024)
17-7496011-G-C			Uncertain significance (Feb 17, 2023)
17-7496017-T-C			Uncertain significance (Mar 14, 2023)
17-7496027-G-T			Likely benign (Aug 01, 2024)
17-7496052-G-T			Uncertain significance (Nov 17, 2023)
17-7496053-G-T		Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities	Uncertain significance (Jan 04, 2024)
17-7496056-G-A		Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities	Uncertain significance (Jul 22, 2023)
17-7496272-G-T			Uncertain significance (Jan 10, 2023)
17-7496295-G-T		Inborn genetic diseases	Uncertain significance (Feb 13, 2024)
17-7496306-G-A		Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities	Uncertain significance (Jun 16, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POLR2A	protein_coding	protein_coding	ENST00000322644	29	30249

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.60e-9	125697	0	51	125748	0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	7.13	512	1.21e+3	0.423	0.0000769	12800
Missense in Polyphen		107	521.33	0.20524		5326
Synonymous	-5.06	625	483	1.29	0.0000317	4039
Loss of Function	7.72	7	82.8	0.0846	0.00000481	959

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000284	0.000208
Ashkenazi Jewish	0.000401	0.000298
East Asian	0.0000545	0.0000544
Finnish	0.000654	0.000323
European (Non-Finnish)	0.000442	0.000273
Middle Eastern	0.0000545	0.0000544
South Asian	0.0000327	0.0000327
Other	0.000831	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Largest and catalytic component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Forms the polymerase active center together with the second largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB1 is part of the core element with the central large cleft, the clamp element that moves to open and close the cleft and the jaws that are thought to grab the incoming DNA template. At the start of transcription, a single-stranded DNA template strand of the promoter is positioned within the central active site cleft of Pol II. A bridging helix emanates from RPB1 and crosses the cleft near the catalytic site and is thought to promote translocation of Pol II by acting as a ratchet that moves the RNA-DNA hybrid through the active site by switching from straight to bent conformations at each step of nucleotide addition. During transcription elongation, Pol II moves on the template as the transcript elongates. Elongation is influenced by the phosphorylation status of the C-terminal domain (CTD) of Pol II largest subunit (RPB1), which serves as a platform for assembly of factors that regulate transcription initiation, elongation, termination and mRNA processing. Regulation of gene expression levels depends on the balance between methylation and acetylation levels of tha CTD-lysines (By similarity). Initiation or early elongation steps of transcription of growth-factors- induced immediate early genes are regulated by the acetylation status of the CTD (PubMed:24207025). Methylation and dimethylation have a repressive effect on target genes expression (By similarity). {ECO:0000250|UniProtKB:P08775, ECO:0000269|PubMed:20231364, ECO:0000269|PubMed:23748380, ECO:0000269|PubMed:24207025, ECO:0000269|PubMed:9852112}.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);RNA polymerase - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Pyrimidine metabolism;Eukaryotic Transcription Initiation;mRNA Processing;FGFR2 alternative splicing;Signaling by FGFR2;DNA Repair;Disease;RNA Pol II CTD phosphorylation and interaction with CE during HIV infection;Signal Transduction;Formation of the HIV-1 Early Elongation Complex;Gene expression (Transcription);Signaling by FGFR;Formation of HIV-1 elongation complex containing HIV-1 Tat;Tat-mediated elongation of the HIV-1 transcript;telomeres telomerase cellular aging and immortality;repression of pain sensation by the transcriptional regulator dream;Abortive elongation of HIV-1 transcript in the absence of Tat;HIV Transcription Elongation;HIV elongation arrest and recovery;the information processing pathway at the ifn beta enhancer;carm1 and regulation of the estrogen receptor;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;Influenza Infection;HIV Transcription Initiation;RNA polymerase II transcribes snRNA genes;RNA Polymerase II Transcription;Metabolism of RNA;Infectious disease;Purine metabolism;RNA Polymerase II Transcription Elongation;mRNA Splicing - Major Pathway;Pyrimidine metabolism;RNA Polymerase II Promoter Escape;RNA Polymerase II Transcription Pre-Initiation And Promoter Opening;TP53 Regulates Transcription of DNA Repair Genes;Signaling by Nuclear Receptors;Transcriptional Regulation by TP53;mRNA Capping;chromatin remodeling by hswi/snf atp-dependent complexes;Formation of the Early Elongation Complex;Estrogen-dependent gene expression;Transcriptional regulation by small RNAs;Signaling by Receptor Tyrosine Kinases;ESR-mediated signaling;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: 0.572

Intolerance Scores

• loftool: 0.260
• rvis_EVS: -3.52
• rvis_percentile_EVS: 0.32

Haploinsufficiency Scores

• pHI: 0.997
• hipred: Y
• hipred_score: 0.662
• ghis: 0.614

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.850

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Polr2a
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; immune system phenotype; respiratory system phenotype; embryo phenotype; neoplasm; normal phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); 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); hematopoietic system phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: mRNA splicing, via spliceosome;transcription, RNA-templated;transcription-coupled nucleotide-excision repair;DNA-templated transcription, termination;regulation of transcription, DNA-templated;transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;transcription elongation from RNA polymerase II promoter;7-methylguanosine mRNA capping;fibroblast growth factor receptor signaling pathway;RNA metabolic process;positive regulation of RNA splicing;snRNA transcription by RNA polymerase II;regulation of gene silencing by miRNA
• Cellular component: Prp19 complex;nucleus;nucleoplasm;RNA polymerase II, core complex;nucleolus;cytoplasm
• Molecular function: RNA polymerase II activity;DNA binding;RNA binding;DNA-directed 5'-3' RNA polymerase activity;RNA-directed 5'-3' RNA polymerase activity;protein binding;protein C-terminus binding;ubiquitin protein ligase binding;metal ion binding;promoter-specific chromatin binding