RRM1

ribonucleotide reductase catalytic subunit M1

Basic information

Region (hg38): 11:4094706-4138932

Links

ENSG00000167325 ∙ NCBI:6240 ∙ OMIM:180410 ∙ HGNC:10451 ∙ Uniprot:P23921 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 6	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	Biochemical; Musculoskeletal	35617047

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RRM1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RRM1 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	2
missense			26	1		27
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	26	1	2

Variants in RRM1

This is a list of pathogenic ClinVar variants found in the RRM1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-4102031-T-C			Uncertain significance (Jun 01, 2024)
11-4106058-A-G		not specified	Uncertain significance (Jan 02, 2024)
11-4106068-T-C		not specified	Uncertain significance (Jun 05, 2024)
11-4107452-T-C		not specified	Uncertain significance (Sep 07, 2022)
11-4107453-A-G		not specified	Uncertain significance (Feb 13, 2024)
11-4107509-T-C			Benign (Dec 31, 2019)
11-4107515-A-G		not specified	Uncertain significance (Sep 29, 2023)
11-4109644-C-T		not specified	Uncertain significance (Oct 12, 2021)
11-4109687-A-G		not specified	Uncertain significance (Dec 20, 2023)
11-4111632-A-G		not specified	Uncertain significance (Jan 31, 2024)
11-4111955-A-C		not specified	Uncertain significance (Dec 12, 2023)
11-4112041-C-G		not specified	Uncertain significance (Jan 02, 2024)
11-4119881-A-G		not specified	Uncertain significance (Nov 08, 2022)
11-4123205-C-T		Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 6	Pathogenic (Dec 07, 2023)
11-4123206-G-A		RRM1-related disorder • Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 6	Uncertain significance (Feb 23, 2023)
11-4123302-G-A		not specified	Uncertain significance (Oct 05, 2023)
11-4126684-G-A		not specified	Uncertain significance (Jul 31, 2023)
11-4126787-G-A		not specified	Uncertain significance (Jun 16, 2024)
11-4127053-C-T		not specified	Uncertain significance (Sep 20, 2023)
11-4127054-G-A			Likely benign (Dec 31, 2019)
11-4127105-T-G		not specified	Uncertain significance (Apr 23, 2024)
11-4127116-C-T		not specified	Uncertain significance (Oct 25, 2023)
11-4127117-C-G		not specified	Uncertain significance (Mar 01, 2024)
11-4127126-G-A		not specified	Uncertain significance (Feb 28, 2024)
11-4127204-C-G		not specified	Uncertain significance (Feb 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RRM1	protein_coding	protein_coding	ENST00000300738	19	44170

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.87e-7	125738	0	5	125743	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.99	196	429	0.457	0.0000219	5249
Missense in Polyphen		31	169.41	0.18299		2108
Synonymous	-0.286	150	146	1.03	0.00000721	1442
Loss of Function	6.16	1	46.2	0.0216	0.00000252	544

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	0.00	0.00
European (Non-Finnish)	0.0000443	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);Glutathione metabolism - Homo sapiens (human);Drug metabolism - other enzymes - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Fluoropyrimidine Pathway, Pharmacokinetics;Gemcitabine Pathway, Pharmacodynamics;Purine Nucleoside Phosphorylase Deficiency;Mercaptopurine Action Pathway;Azathioprine Action Pathway;Xanthine Dehydrogenase Deficiency (Xanthinuria);Adenylosuccinate Lyase Deficiency;AICA-Ribosiduria;Thioguanine Action Pathway;Adenine phosphoribosyltransferase deficiency (APRT);Mitochondrial DNA depletion syndrome;Myoadenylate deaminase deficiency;Purine Metabolism;Gemcitabine Action Pathway;Molybdenum Cofactor Deficiency;Adenosine Deaminase Deficiency;Gemcitabine Metabolism Pathway;Gout or Kelley-Seegmiller Syndrome;Lesch-Nyhan Syndrome (LNS);Xanthinuria type I;Xanthinuria type II;Fluoropyrimidine Activity;Retinoblastoma (RB) in Cancer;Pyrimidine metabolism;Nucleotide Metabolism;pyrimidine deoxyribonucleotides <i>de novo</i> biosynthesis;Metabolism of nucleotides;Interconversion of nucleotide di- and triphosphates;Metabolism;Purine nucleotides nucleosides metabolism;superpathway of purine nucleotide salvage;Pyrimidine nucleotides nucleosides metabolism;superpathway of pyrimidine deoxyribonucleotides <i>de novo</i> biosynthesis;pyrimidine deoxyribonucleotides biosynthesis from CTP;guanosine deoxyribonucleotides <i>de novo</i> biosynthesis;guanosine nucleotides <i>de novo</i> biosynthesis;adenosine deoxyribonucleotides <i>de novo</i> biosynthesis;purine nucleotides <i>de novo</i> biosynthesis;E2F transcription factor network (Consensus)

Recessive Scores

• pRec: 0.352

Intolerance Scores

• loftool: 0.149
• rvis_EVS: -0.64
• rvis_percentile_EVS: 16.53

Haploinsufficiency Scores

• pHI: 0.991
• hipred: Y
• hipred_score: 0.859
• ghis: 0.699

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.982

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rrm1
• Phenotype: 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)

Zebrafish Information Network

• Gene name: rrm1
• Affected structure: trunk
• Phenotype tag: abnormal
• Phenotype quality: sigmoid

Gene ontology

• Biological process: mitotic cell cycle;pyrimidine nucleobase metabolic process;DNA replication;male gonad development;deoxyribonucleotide biosynthetic process;response to ionizing radiation;cell proliferation in forebrain;protein heterotetramerization;oxidation-reduction process;retina development in camera-type eye
• Cellular component: nuclear envelope;cytosol;ribonucleoside-diphosphate reductase complex;cell projection;neuronal cell body
• Molecular function: ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor;protein binding;ATP binding;identical protein binding;disordered domain specific binding