POLR1A

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

Basic information

Region (hg38): 2:86020216-86106155

Links

ENSG00000068654 ∙ NCBI:25885 ∙ OMIM:616404 ∙ HGNC:17264 ∙ Uniprot:O95602 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• acrofacial dysostosis Cincinnati type (Strong), mode of inheritance: AD
• choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome (Supportive), mode of inheritance: AR
• acrofacial dysostosis Cincinnati type (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Acrofacial dysostosis, Cincinnati type; Leukodystrophy, hypomyelinating, 27	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	Craniofacial; Musculoskeletal; Neurologic	25913037; 28051070; 36917474

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POLR1A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POLR1A 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	200	15	217
missense		1	367	10	10	388
nonsense			6			6
start loss						0
frameshift		1	2			3
inframe indel			1			1
splice donor/acceptor (+/-2bp)			4			4
splice region			13	27	5	45
non coding			6	94	48	148
Total	0	2	388	304	73

Variants in POLR1A

This is a list of pathogenic ClinVar variants found in the POLR1A region.

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

Position	Type	Phenotype	Significance	ClinVar
2-86027434-G-C			Uncertain significance (Jan 03, 2022)
2-86027446-C-T			Uncertain significance (Jun 22, 2022)
2-86027447-G-A			Likely benign (Mar 24, 2023)
2-86027461-C-T			Uncertain significance (Sep 21, 2023)
2-86027471-G-A			Likely benign (Nov 29, 2022)
2-86027482-C-T		Inborn genetic diseases	Uncertain significance (Jul 10, 2023)
2-86027507-C-G			Likely benign (Jul 26, 2022)
2-86027510-C-G			Uncertain significance (Nov 27, 2023)
2-86027516-G-A			Likely benign (Dec 28, 2023)
2-86027523-C-T			Uncertain significance (Aug 17, 2021)
2-86027528-C-T			Likely benign (Jun 30, 2022)
2-86027529-A-G			Likely benign (Oct 06, 2022)
2-86027536-C-T			Benign (Oct 13, 2023)
2-86027871-G-T			Likely benign (May 26, 2023)
2-86027876-C-T			Likely benign (Jan 22, 2023)
2-86027877-G-A			Likely benign (Feb 04, 2022)
2-86027879-A-G			Uncertain significance (Dec 22, 2023)
2-86027892-G-A			Likely benign (Oct 23, 2023)
2-86027901-C-T			Likely benign (May 02, 2018)
2-86027920-G-A			Uncertain significance (Aug 26, 2022)
2-86027946-G-C			Likely benign (Feb 22, 2023)
2-86027958-C-T		POLR1A-related disorder	Likely benign (Dec 24, 2023)
2-86027959-C-T			Uncertain significance (May 05, 2023)
2-86027960-G-A		Inborn genetic diseases	Uncertain significance (Sep 23, 2023)
2-86027972-G-A			Uncertain significance (Oct 24, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POLR1A	protein_coding	protein_coding	ENST00000263857	34	85940

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000202	124765	0	49	124814	0.000196

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.95	750	1.01e+3	0.739	0.0000612	11278
Missense in Polyphen		268	497.29	0.53892		5537
Synonymous	1.03	394	421	0.936	0.0000277	3345
Loss of Function	7.50	16	94.8	0.169	0.00000546	1027

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000485	0.000485
Ashkenazi Jewish	0.00	0.00
East Asian	0.000168	0.000167
Finnish	0.000233	0.000232
European (Non-Finnish)	0.000133	0.000132
Middle Eastern	0.000168	0.000167
South Asian	0.000394	0.000392
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. Largest and catalytic core component of RNA polymerase I which synthesizes ribosomal RNA precursors. 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 I. A bridging helix emanates from RPA1 and crosses the cleft near the catalytic site and is thought to promote translocation of Pol I 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). {ECO:0000250|UniProtKB:P10964}.
• Disease: DISEASE: Acrofacial dysostosis, Cincinnati type (AFDCIN) [MIM:616462]: A form of acrofacial dysostosis, a group of disorders which are characterized by malformation of the craniofacial skeleton and, in some patients, the limbs. {ECO:0000269|PubMed:25913037}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);RNA polymerase - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Nucleotide Excision Repair ;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: 0.220

Intolerance Scores

• loftool: 0.404
• rvis_EVS: 0.09
• rvis_percentile_EVS: 60.33

Haploinsufficiency Scores

• pHI: 0.234
• hipred: Y
• hipred_score: 0.706
• ghis: 0.516

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.379

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Polr1a

Zebrafish Information Network

• Gene name: polr1a
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: quality

Gene ontology

• Biological process: transcription initiation from RNA polymerase I promoter;termination of RNA polymerase I transcription;positive regulation of gene expression, epigenetic;negative regulation of protein localization to nucleolus
• Cellular component: nucleoplasm;RNA polymerase I complex
• Molecular function: RNA polymerase I activity;DNA binding;chromatin binding;DNA-directed 5'-3' RNA polymerase activity;protein binding;zinc ion binding