POLR3K

Last update 08 May 2025

Basic Info

Synonyms

C11, DNA-directed RNA polymerase III subunit K, DNA-directed RNA polymerase III subunit RPC10

+ [9]

Introduction

Core component of RNA polymerase III (Pol III) which synthesizes small non-coding RNAs using the four ribonucleoside triphosphates as substrates (PubMed:20413673, PubMed:30584594, PubMed:33335104, PubMed:33558764, PubMed:33558766, PubMed:33674783, PubMed:34675218). Can mediate Pol I proofreading of the nascent RNA transcript. Anchors into the Pol III active site to constantly monitor transcription fidelity, cleaves mis-incorporated 5'-ribonucleotides and restarts the transcription process. Once Pol III reaches the poly(dT) termination signal, can induce Pol III clamp opening and transcription termination (By similarity) (PubMed:33335104, PubMed:33558764, PubMed:33558766, PubMed:33674783, PubMed:34675218). Pol III plays an important role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as a 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 (PubMed:19609254, PubMed:19631370).

100 Clinical Results associated with POLR3K

100 Translational Medicine associated with POLR3K

0 Patents (Medical) associated with POLR3K

Literatures (Medical) associated with POLR3K

03 Jul 2024·The Clinical Neuropsychologist

Case report: Neuropsychological assessment in a patient with 4H leukodystrophy

Article

Author: Hagy, Hannah A ; Haneda, Aya ; Lacy, Maureen ; Hoots, Jennifer K

Objective: POLR3-HLD or 4H leukodystrophy is an autosomal recessive disorder characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, and caused by variants in POLR3A, POLR3B, POLR1C, or POLR3K genes. Neurological and non-neurological clinical features and disease severity vary. While previous studies reference variable cognition, this is the first report of 4H detailing a comprehensive neuropsychological assessment. Method: The current study presents a 20-year-old, English-speaking, right-handed, non-Hispanic White female with 12 years of education with genetically confirmed 4H POLR3B-related leukodystrophy without hormonal replacement treatment. Results: At age 4, developmental delays, ataxia, hearing loss, and abnormal dentition were present. Imaging, endocrinology, and neurologic examinations revealed hypomyelination, reduced cerebellar volume, delayed bone age density, osteopenia, and evidence of adrenarche without signs of true puberty. Neuropsychological assessment at age 20 revealed global cognitive impairment with intellectual, attention, verbal memory retrieval, construction, executive (e.g. processing speed, sustained attention) and math computation deficits, along with behavioral dysregulation. Conclusion: We present the first detailed neuropsychological assessment of a patient with 4H leukodystrophy. The neuropsychological assessment revealed cognitive and behavioral dysexecutive deficits aligning with hypomyelination observed on imaging. Further longitudinal studies are needed to shed light on the neurobehavioral presentation associated with this disorder to assist care providers, patients, and their families.

01 Jan 2024·Human Mutation

Novel Pathogenic Variants in POLR3K Cause POLR3‐Related Leukodystrophy

Article

Author: Müller, Christoph W. ; Maegawa, Gustavo H B ; Misiaszek, Agata D ; Pastinen, Tomi ; Misiaszek, Agata D. ; Thiffault, Isabelle ; Tran, Luan T. ; Müller, Christoph W ; Maegawa, Gustavo H. B. ; Tran, Luan T ; Macintosh, Julia ; Bernard, Geneviève ; Lambert, Gabrielle ; Guerrero, Kether ; Perrier, Stefanie

POLR3‐related hypomyelinating leukodystrophy (POLR3‐HLD) is a rare inherited neurological disorder caused by biallelic pathogenic variants in specific genes encoding subunits of RNA polymerase III (Pol III). Here, we report the third patient worldwide with pathogenic variants in POLR3K and clinical features consistent with POLR3‐HLD. The female patient presented with mild intellectual and behavioural disturbances in childhood, as well as growth delay, with brain MRI revealing diffuse hypomyelination and a pattern consistent with POLR3‐HLD. In adolescence, she manifested minor motor dysfunction. Next‐generation sequencing revealed a paternally inherited missense variant in POLR3K (c.322G>T; p.D108Y) and a maternally inherited large deletion, spanning approximately 17.8 kb from chr16:30,362‐48,162. The missense variant is located at the C‐terminus position of the protein and is predicted to impair residue interactions and cause steric interference in enzyme conformational changes. The large deletion encompasses the third and last exon of POLR3K, leading to a likely amorphic truncated protein product lacking the final 42 amino acids from the total 108 amino acid–length protein. Studies of RNA‐level expression showed a significant reduction in the levels of POLR3K RNA in the patient compared to the control. In considering whether the transcriptional function of Pol III was affected, the expression of several Pol III‐transcribed RNAs was measured, where the levels of several distinct tRNAs were significantly reduced in the patient while the expression of other RNA transcripts was not decreased, suggesting that Pol III retains partial function. This study provides further evidence for the association of pathogenic variants in POLR3K with POLR3‐HLD, expanding the spectrum of pathogenic variants in genes encoding for Pol III subunits associated with this disease.

15 Dec 2023·The Journal of Maternal-Fetal & Neonatal Medicine

Identification of a novel 91.5 kb-deletion (αα) ^FJ in the α-globin gene cluster using single-molecule real-time (SMRT) sequencing

Article

Author: Zhang, Siwen ; He, Qianqian ; Guo, Danhua ; Xu, Liangpu ; Huang, Hailong ; Chen, Lingji ; Zhang, Min ; Lin, Na ; Zheng, Junhao ; Chen, Meihuan

OBJECTIVESTo present a novel 91.5-kb deletion of the α-globin gene cluster (αα)^FJ identified by genetic assay and prenatal diagnosis in a Chinese family.SUBJECTS AND METHODSThe proband was a 34-year-old G3P1 (Gravida 3, Para 1) female at the gestational age of 21⁺ weeks with a history of an edematous fetus. A routine genetic assay (reverse dot blot hybridization, RDB) was performed to detect common thalassemia mutations. Multiplex ligation-dependent probe amplification (MLPA) and single-molecule real-time technology (SMRT) were used to detect rare thalassemia mutations.RESULTSThe hematological phenotypes of the proband, her mother, elder sister, husband, daughter, and nephew were consistent with the phenotype of α-thalassemia trait. No mutations were found in these family members by RDB, except for the proband's husband who carried an α-globin gene deletion --^SEA/αα. MLPA results showed that the proband and other α-thalassemia-suspected relatives had heterozygous deletions around the POLR3K-3-463nt, HS40-178nt, and HBA-HS40-382nt probes. The 5'-breakpoint was out of probe scope and could not be determined. SMRT was performed and a 91.5-kb deletion (NC_000016.10: g.39268_130758del) in the α-globin gene cluster (αα)^FJ was identified in the proband and other suspected relatives, which could explain their phenotypes. At the proband's gestational age of 22⁺ weeks, an amniotic fluid sample was collected and analyzed. As only the 91.5-kb deletion (αα)^FJ was identified in the fetus with RDB, MLPA, and SMRT. The proband was suggested to continue the pregnancy.CONCLUSIONWe first reported a 91.5-kb deletion (NC_000016.10: g.hg38-chr16:39268-_130758del) of the HS-40 region in the α-globin gene cluster (αα)^FJ identified in a Chinese family. Since the HS-40 loss of heterozygosity in combination with the heterozygous deletion --^SEA might result in Hb Bart's hydrops fetalis, routine genetic assay, and SMRT were recommended to individuals at risk for prenatal diagnosis.

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