POLR1C

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

Basic information

Region (hg38): 6:43509702-43562419

Links

ENSG00000171453 ∙ NCBI:9533 ∙ OMIM:610060 ∙ HGNC:20194 ∙ Uniprot:O15160 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypomyelinating leukodystrophy 11 (Strong), mode of inheritance: AR
• Treacher Collins syndrome 3 (Moderate), mode of inheritance: AR
• Treacher-Collins syndrome (Supportive), mode of inheritance: AD
• hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome (Supportive), mode of inheritance: AR
• hypomyelinating leukodystrophy 11 (Strong), mode of inheritance: AR
• Treacher Collins syndrome 3 (Strong), mode of inheritance: AR
• Treacher Collins syndrome 3 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Treacher Collins syndrome 3	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Dental; Neurologic	21131976; 26151409

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POLR1C gene.

• Hypomyelinating leukodystrophy 11 (15 variants)
• not provided (7 variants)
• Treacher Collins syndrome 3 (2 variants)
• Treacher Collins syndrome 3;Hypomyelinating leukodystrophy 11 (1 variants)
• Hypomyelinating leukodystrophy 11;Treacher Collins syndrome 3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POLR1C 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			3	25		28
missense	9	5	74	4	3	95
nonsense	3	2				5
start loss						0
frameshift	4	2			1	7
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)	2		1			3
splice region			5	5		10
non coding			90	117	58	265
Total	18	10	169	146	62

Highest pathogenic variant AF is 0.0000723

Variants in POLR1C

This is a list of pathogenic ClinVar variants found in the POLR1C region.

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

Position	Type	Phenotype	Significance	ClinVar
6-43509740-C-T		not specified	Uncertain significance (Mar 14, 2023)
6-43509763-A-G		not specified	Uncertain significance (Sep 20, 2023)
6-43512193-C-A		not specified	Uncertain significance (Feb 21, 2024)
6-43512196-C-T		not specified	Uncertain significance (Dec 09, 2023)
6-43512208-C-T		not specified	Uncertain significance (Jan 20, 2023)
6-43512287-G-T		not specified	Uncertain significance (Jun 02, 2023)
6-43512457-T-C		not specified	Uncertain significance (Oct 13, 2021)
6-43512539-C-T		not specified	Uncertain significance (Oct 26, 2021)
6-43512544-C-T		not specified	Uncertain significance (Jul 14, 2021)
6-43512563-C-T		not specified	Uncertain significance (May 12, 2024)
6-43512765-C-T		not specified	Uncertain significance (Oct 05, 2021)
6-43512831-T-C		not specified	Uncertain significance (Jun 06, 2023)
6-43513095-T-A		not specified	Uncertain significance (May 17, 2023)
6-43513104-C-T		not specified	Uncertain significance (Apr 06, 2023)
6-43513143-C-T		not specified	Uncertain significance (Jun 17, 2024)
6-43513593-G-A		not specified	Uncertain significance (Nov 08, 2022)
6-43513620-T-C		not specified	Uncertain significance (Sep 12, 2023)
6-43515615-C-A		not specified	Uncertain significance (Jun 03, 2024)
6-43515971-G-A		not specified	Uncertain significance (Aug 02, 2023)
6-43515978-C-T		not specified	Uncertain significance (Jan 10, 2023)
6-43515980-G-C		not specified	Uncertain significance (Apr 18, 2024)
6-43515987-C-T		not specified	Uncertain significance (Apr 15, 2024)
6-43516003-G-A			Likely benign (Oct 01, 2021)
6-43516009-G-A			Likely benign (Jan 01, 2023)
6-43516071-T-A		not specified	Uncertain significance (Mar 30, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POLR1C	protein_coding	protein_coding	ENST00000372389	9	19884

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.32e-10	0.132	125706	0	42	125748	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.44	252	195	1.29	0.0000121	2272
Missense in Polyphen		79	64.096	1.2325		734
Synonymous	-1.58	89	71.9	1.24	0.00000399	699
Loss of Function	0.335	15	16.5	0.911	9.74e-7	188

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000242	0.000242
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.000255	0.000246
Middle Eastern	0.000326	0.000326
South Asian	0.0000980	0.0000980
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 and III which synthesize ribosomal RNA precursors and small RNAs, such as 5S rRNA and tRNAs, respectively. RPAC1 is part of the Pol core element with the central large cleft and probably a clamp element that moves to open and close the cleft (By similarity). {ECO:0000250|UniProtKB:P07703, ECO:0000305|PubMed:26151409}.
• Disease: DISEASE: Treacher Collins syndrome 3 (TCS3) [MIM:248390]: A form of Treacher Collins syndrome, a disorder of craniofacial development. Treacher Collins syndrome is characterized by a combination of bilateral downward slanting of the palpebral fissures, colobomas of the lower eyelids with a paucity of eyelashes medial to the defect, hypoplasia of the facial bones, cleft palate, malformation of the external ears, atresia of the external auditory canals, and bilateral conductive hearing loss. {ECO:0000269|PubMed:21131976, ECO:0000269|PubMed:26151409}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Leukodystrophy, hypomyelinating, 11 (HLD11) [MIM:616494]: An autosomal recessive neurologic disorder characterized by brain hypomyelination, delayed psychomotor development, intellectual disability, tremor and other neurologic symptoms. Some patients may additionally manifest non-neurologic features, particularly dental abnormalities and hypogonadotropic hypogonadism. {ECO:0000269|PubMed:26151409}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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;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: 0.176

Intolerance Scores

• loftool: 0.292
• rvis_EVS: -0.09
• rvis_percentile_EVS: 46.74

Haploinsufficiency Scores

• pHI: 0.506
• hipred: Y
• hipred_score: 0.608
• ghis: 0.585

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.988

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Polr1c

Zebrafish Information Network

• Gene name: polr1c
• Affected structure: neuroepithelial cell
• Phenotype tag: abnormal
• Phenotype quality: apoptotic

Gene ontology

• Biological process: transcription by RNA polymerase I;transcription initiation from RNA polymerase I promoter;termination of RNA polymerase I transcription;transcription by RNA polymerase III;positive regulation of gene expression, epigenetic
• Cellular component: nucleus;nucleoplasm;RNA polymerase III complex;RNA polymerase I complex;cytosol
• Molecular function: RNA polymerase I activity;RNA polymerase III activity;DNA binding;DNA-directed 5'-3' RNA polymerase activity;protein binding;protein dimerization activity