POLR1D

RNA polymerase I and III subunit D, the group of RNA polymerase subunits

Basic information

Region (hg38): 13:27620741-27744237

Links

ENSG00000186184 ∙ NCBI:51082 ∙ OMIM:613715 ∙ HGNC:20422 ∙ Uniprot:P0DPB5, P0DPB6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Treacher Collins syndrome 2 (Definitive), mode of inheritance: AD
• Treacher Collins syndrome 2 (Strong), mode of inheritance: AD
• Treacher-Collins syndrome (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Treacher Collins syndrome 2	AD/AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Dental	21131976; 24603435; 25790162

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POLR1D gene.

• not provided (56 variants)
• Treacher Collins syndrome 2 (7 variants)
• Inborn genetic diseases (4 variants)
• POLR1D-related condition (3 variants)
• not specified (1 variants)
• Hearing impairment (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POLR1D 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	6	8
missense		1	24		1	26
nonsense	1	1	1			3
start loss						0
frameshift	1	4	1			6
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				7	15	22
Total	2	6	26	9	22

Variants in POLR1D

This is a list of pathogenic ClinVar variants found in the POLR1D region.

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

Position	Type	Phenotype	Significance	ClinVar
13-27621695-C-T			Benign (Dec 12, 2018)
13-27621752-G-A			Benign (Dec 12, 2018)
13-27621835-C-T			Benign (Oct 16, 2018)
13-27621874-C-A			Benign (Oct 16, 2018)
13-27621877-C-T			Benign (Apr 04, 2019)
13-27621896-G-C			Benign (Dec 10, 2018)
13-27622027-G-A			Benign (Dec 06, 2023)
13-27622067-G-T			Benign (Dec 17, 2018)
13-27622184-A-G			Benign (Nov 29, 2018)
13-27622261-G-A			Benign (Jan 02, 2019)
13-27622682-G-C			Likely benign (Feb 16, 2019)
13-27622695-G-A			Benign (Dec 17, 2018)
13-27622698-A-T			Likely benign (Dec 12, 2018)
13-27622856-A-G			Likely benign (Jul 03, 2023)
13-27622867-G-A			Likely benign (Aug 27, 2023)
13-27622904-C-T			Uncertain significance (Apr 26, 2019)
13-27622906-G-GA		Treacher Collins syndrome 2	Likely pathogenic (Feb 23, 2023)
13-27622914-G-A		POLR1D-related disorder	Likely benign (Mar 01, 2019)
13-27622935-G-GGT		Treacher Collins syndrome 2	Pathogenic (Jan 01, 2011)
13-27622936-GTCCAGGCAGCTGGAACAGATAGACACTGT-G		Treacher Collins syndrome 2	Likely pathogenic (Sep 01, 2022)
13-27622945-G-C		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)
13-27622945-GCTGGAACAGATAGACACTGTGTGACATTTGTATTGCACGAGGAAGA-G			Likely pathogenic (Aug 11, 2017)
13-27622952-C-T			Uncertain significance (Dec 13, 2023)
13-27622956-T-TA			Pathogenic (Jan 16, 2022)
13-27622975-G-GT		POLR1D-related disorder	Likely pathogenic (Dec 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POLR1D	protein_coding	protein_coding	ENST00000302979	2	46646

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.364	0.591	125744	0	1	125745	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.169	70	74.1	0.945	0.00000396	880
Missense in Polyphen		15	19.166	0.78263		252
Synonymous	0.987	21	27.6	0.761	0.00000153	245
Loss of Function	1.57	1	4.66	0.214	2.62e-7	58

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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;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;RNA Polymerase III Transcription Termination;RNA Polymerase III Chain Elongation;TNFalpha;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: 0.163

Intolerance Scores

• loftool: 0.245
• rvis_EVS: -0.32
• rvis_percentile_EVS: 31.69

Haploinsufficiency Scores

• pHI: 0.206
• hipred: Y
• hipred_score: 0.778
• ghis: 0.535

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.909

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Polr1d

Zebrafish Information Network

• Gene name: polr1d
• Affected structure: neuroepithelial cell
• Phenotype tag: abnormal
• Phenotype quality: apoptotic

Gene ontology

• Biological process: transcription, DNA-templated
• Cellular component: RNA polymerase III complex;RNA polymerase I complex
• Molecular function: RNA polymerase I activity;RNA polymerase III activity;DNA binding;DNA-directed 5'-3' RNA polymerase activity;protein binding;protein dimerization activity