POLRMT

RNA polymerase mitochondrial, the group of Pentatricopeptide repeat containing

Basic information

Region (hg38): 19:617221-633537

Links

ENSG00000099821 ∙ NCBI:5442 ∙ OMIM:601778 ∙ HGNC:9200 ∙ Uniprot:O00411 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined oxidative phosphorylation deficiency 55 (Strong), mode of inheritance: AR
• combined oxidative phosphorylation deficiency 55 (Limited), mode of inheritance: AD
• combined oxidative phosphorylation deficiency 55 (Limited), mode of inheritance: AR
• combined oxidative phosphorylation deficiency 55 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 55	AD/AR	Biochemical; Renal	The condition can involve renal and other manifestations, and medical management for this and other manifestations (eg, with elemental phosphorus, calcitriol, and sodium citrate), has been described as benefiical, including related to musculoskeletal sequelae	Biochemical; Musculoskeletal; Neurologic; Renal	24386581; 33602924

ClinVar

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

• not_specified (293 variants)
• not_provided (56 variants)
• Combined_oxidative_phosphorylation_deficiency_55 (49 variants)
• POLRMT-related_disorder (13 variants)
• Neurodevelopmental_disorder (1 variants)
• Autosomal_dominant_progressive_external_ophthalmoplegia (1 variants)
• Progressive_sclerosing_poliodystrophy (1 variants)
• Long_QT_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POLRMT gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005035.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	25	2	29
missense	5		288	32	4	329
nonsense	2	3	1			6
start loss						0
frameshift	1		1			2
splice donor/acceptor (+/-2bp)	1	1	1			3
Total	9	4	293	57	6

Highest pathogenic variant AF is 0.000699868

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POLRMT	protein_coding	protein_coding	ENST00000588649	21	16375

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.74e-20	0.448	125625	0	108	125733	0.000430

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.87	933	786	1.19	0.0000567	7758
Missense in Polyphen		301	275.09	1.0942		2690
Synonymous	-8.07	550	356	1.54	0.0000267	2512
Loss of Function	1.89	39	54.0	0.722	0.00000248	601

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000636	0.000613
Ashkenazi Jewish	0.00	0.00
East Asian	0.000502	0.000489
Finnish	0.000125	0.0000924
European (Non-Finnish)	0.000429	0.000404
Middle Eastern	0.000502	0.000489
South Asian	0.00122	0.00118
Other	0.000336	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA-dependent RNA polymerase catalyzes the transcription of mitochondrial DNA into RNA using the four ribonucleoside triphosphates as substrates. {ECO:0000269|PubMed:21278163}.
• Pathway: Mitochondrial biogenesis;Mitochondrial Gene Expression;Gene expression (Transcription);Purine metabolism;Pyrimidine metabolism;Mitochondrial transcription initiation;Transcription from mitochondrial promoters (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.770
• rvis_EVS: -0.02
• rvis_percentile_EVS: 51.92

Haploinsufficiency Scores

• pHI: 0.115
• hipred: N
• hipred_score: 0.146
• ghis: 0.502

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.847

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Polrmt
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cellular phenotype; muscle phenotype

Gene ontology

• Biological process: mitochondrial transcription;transcription initiation from mitochondrial promoter;mitochondrion organization
• Cellular component: mitochondrion;mitochondrial matrix;protein-containing complex;mitochondrial DNA-directed RNA polymerase complex;mitochondrial nucleoid
• Molecular function: mitochondrial promoter sequence-specific DNA binding;RNA binding;DNA-directed 5'-3' RNA polymerase activity;protein binding;sequence-specific DNA binding