POLR3K

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

Basic information

Region (hg38): 16:46407-53608

Links

ENSG00000161980 ∙ NCBI:51728 ∙ OMIM:606007 ∙ HGNC:14121 ∙ Uniprot:Q9Y2Y1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• leukodystrophy, hypomyelinating, 21 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukodystrophy, hypomyelinating 21	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	Gastrointestinal; Genitourinary; Neurologic	30584594

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POLR3K gene.

• Leukodystrophy, hypomyelinating, 21 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POLR3K 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		1
missense	1		5			6
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	1	0	6	1	0

Variants in POLR3K

This is a list of pathogenic ClinVar variants found in the POLR3K region.

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

Position	Type	Phenotype	Significance	ClinVar
16-47435-C-A		Leukodystrophy, hypomyelinating, 21	Pathogenic (-)
16-47549-G-C		not specified	Uncertain significance (Nov 18, 2021)
16-47554-G-A		not specified	Uncertain significance (Jan 26, 2022)
16-51591-C-A		not specified	Uncertain significance (Jun 18, 2021)
16-51635-C-T		Leukodystrophy, hypomyelinating, 21	Uncertain significance (Nov 17, 2021)
16-51636-G-A		Leukodystrophy, hypomyelinating, 21	Pathogenic (May 04, 2021)
16-53480-C-G		not specified	Uncertain significance (Nov 13, 2023)
16-53486-ATGT-A		Leukodystrophy, hypomyelinating, 21	Uncertain significance (Nov 17, 2021)
16-53551-C-G			Likely benign (Jan 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POLR3K	protein_coding	protein_coding	ENST00000293860	3	7222

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.108	0.786	125743	0	4	125747	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0886	70	67.9	1.03	0.00000383	706
Missense in Polyphen		13	15.418	0.84318		189
Synonymous	-1.01	30	23.8	1.26	0.00000122	199
Loss of Function	1.26	2	5.07	0.394	2.17e-7	56

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000616	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000180	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
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. Component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. 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 (By similarity). {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;Eukaryotic Transcription Initiation;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: 0.111

Intolerance Scores

• loftool: 0.180
• rvis_EVS: -0.19
• rvis_percentile_EVS: 39.68

Haploinsufficiency Scores

• pHI: 0.723
• hipred: Y
• hipred_score: 0.667
• ghis: 0.686

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.694

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Polr3k

Zebrafish Information Network

• Gene name: polr3k
• Affected structure: hematopoietic multipotent progenitor cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: transcription by RNA polymerase III;termination of RNA polymerase III transcription;tRNA 3'-trailer cleavage;innate immune response;defense response to virus
• Cellular component: nucleoplasm;RNA polymerase III complex;nucleolus;cytosol
• Molecular function: RNA polymerase III activity;nucleic acid binding;DNA-directed 5'-3' RNA polymerase activity;zinc ion binding