POLR3A

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

Basic information

Region (hg38): 10:77953147-78029522

Links

ENSG00000148606 ∙ NCBI:11128 ∙ OMIM:614258 ∙ HGNC:30074 ∙ Uniprot:O14802 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Wiedemann-Rautenstrauch syndrome (Supportive), mode of inheritance: AR
• odontoleukodystrophy (Supportive), mode of inheritance: AR
• hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome (Supportive), mode of inheritance: AR
• leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome (Supportive), mode of inheritance: AR
• hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome (Supportive), mode of inheritance: AR
• tremor-ataxia-central hypomyelination syndrome (Supportive), mode of inheritance: AR
• odontoleukodystrophy (Definitive), mode of inheritance: AR
• Wiedemann-Rautenstrauch syndrome (Strong), mode of inheritance: AR
• leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism; Wiedemann-Rautenstrauch syndrome	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	Craniofacial; Dental; Endocrine; Musculoskeletal; Neurologic; Pulmonary	12605447; 17159124; 20640464; 21855841; 25339210; 27612211; 30323018; 30414627; 30450527

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POLR3A gene.

• not provided (822 variants)
• Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome (269 variants)
• Inborn genetic diseases (51 variants)
• Leukodystrophy (41 variants)
• Neonatal pseudo-hydrocephalic progeroid syndrome (31 variants)
• not specified (12 variants)
• Pol III-related leukodystrophy (11 variants)
• POLR3A-related disorders (8 variants)
• POLR3A-related condition (6 variants)
• POLR3A-related neurological disorders (5 variants)
• Wiedemann-Rautenstrauch-like progeroid syndrome (3 variants)
• Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome;Neonatal pseudo-hydrocephalic progeroid syndrome (3 variants)
• Diamond-Blackfan anemia (2 variants)
• Hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism;Neonatal pseudo-hydrocephalic progeroid syndrome;Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome (2 variants)
• Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome (1 variants)
• Hypomyelinating leukodystrophy 4 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POLR3A 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		1	7	158	9	175
missense	1	12	304	8		325
nonsense	18	10				28
start loss		1				1
frameshift	15	6				21
inframe indel			7			7
splice donor/acceptor (+/-2bp)	4	13	2			19
splice region	1	2	30	33	2	68
non coding		2	54	147	75	278
Total	38	45	374	313	84

Highest pathogenic variant AF is 0.0000527

Variants in POLR3A

This is a list of pathogenic ClinVar variants found in the POLR3A region.

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

Position	Type	Phenotype	Significance	ClinVar
10-77975273-A-C		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Uncertain significance (Jan 13, 2018)
10-77975288-C-G		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Uncertain significance (Jan 13, 2018)
10-77975344-G-T		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Uncertain significance (Jan 13, 2018)
10-77975405-G-T		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Uncertain significance (Jan 13, 2018)
10-77975439-G-A		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Likely benign (Jan 12, 2018)
10-77975513-T-C		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Benign (Jan 13, 2018)
10-77975525-C-G		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Uncertain significance (Jan 12, 2018)
10-77975525-C-T		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Uncertain significance (Jan 12, 2018)
10-77975533-C-T		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Uncertain significance (Jan 13, 2018)
10-77975554-C-T		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Likely benign (Jan 12, 2018)
10-77975605-G-A		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Uncertain significance (Jan 13, 2018)
10-77975609-G-A		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Uncertain significance (Jan 12, 2018)
10-77975611-T-C		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Uncertain significance (Jan 13, 2018)
10-77975616-C-T		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Benign (Jan 13, 2018)
10-77975625-G-A		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Benign (Jan 12, 2018)
10-77975653-A-C		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Uncertain significance (Jan 13, 2018)
10-77975696-C-T		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Benign (Jan 12, 2018)
10-77975697-GCAGAAGACAA-G		Pol III-related leukodystrophy	Uncertain significance (Jun 14, 2016)
10-77975715-C-T		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Benign (Jan 13, 2018)
10-77975760-C-G		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Benign (Jan 12, 2018)
10-77975783-C-T		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Benign (Jan 13, 2018)
10-77975798-G-C		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Benign (Jan 13, 2018)
10-77975835-G-A		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Uncertain significance (Jan 13, 2018)
10-77975837-TG-T		Pol III-related leukodystrophy	Uncertain significance (Jun 14, 2016)
10-77975871-C-T		Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POLR3A	protein_coding	protein_coding	ENST00000372371	31	54397

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.28e-23	0.800	125603	0	145	125748	0.000577

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.31	574	752	0.763	0.0000442	9159
Missense in Polyphen		120	246.3	0.48721		2910
Synonymous	0.527	283	295	0.961	0.0000189	2689
Loss of Function	2.40	47	68.4	0.687	0.00000402	835

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000850	0.000850
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000816	0.000816
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000695	0.000695
Middle Eastern	0.000816	0.000816
South Asian	0.000853	0.000850
Other	0.000491	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 core component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. Forms the polymerase active center together with the second largest subunit. A single-stranded DNA template strand of the promoter is positioned within the central active site cleft of Pol III. A bridging helix emanates from RPC1 and crosses the cleft near the catalytic site and is thought to promote translocation of Pol III 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 (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}.
• 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;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: 0.122

Intolerance Scores

• loftool: 0.761
• rvis_EVS: -1.92
• rvis_percentile_EVS: 1.93

Haploinsufficiency Scores

• pHI: 0.494
• hipred: Y
• hipred_score: 0.639
• ghis: 0.591

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Polr3a
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

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