RRM2

ribonucleotide reductase regulatory subunit M2

Basic information

Region (hg38): 2:10120697-10211725

Previous symbols: [ "C2orf48" ]

Links

ENSG00000171848 ∙ NCBI:6241 ∙ OMIM:180390 ∙ HGNC:10452 ∙ Uniprot:P31350 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RRM2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RRM2 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			7			7
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1			1
Total	0	0	8	0	1

Variants in RRM2

This is a list of pathogenic ClinVar variants found in the RRM2 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-10122775-G-T		not specified	Uncertain significance (Jun 02, 2023)
2-10122837-C-G		not specified	Uncertain significance (Dec 26, 2023)
2-10122846-G-A			Benign (Jan 22, 2018)
2-10122887-A-G		not specified	Uncertain significance (May 08, 2024)
2-10123390-A-G		not specified	Uncertain significance (Apr 20, 2023)
2-10123478-A-G		not specified	Uncertain significance (Dec 28, 2022)
2-10123851-T-C		not specified	Uncertain significance (Jul 25, 2023)
2-10124835-A-G		not specified	Uncertain significance (Jan 22, 2024)
2-10126901-C-T		not specified	Uncertain significance (Aug 23, 2021)
2-10142258-A-T		Inborn genetic diseases	Uncertain significance (Oct 19, 2021)
2-10210386-C-A		not specified	Uncertain significance (Aug 10, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RRM2	protein_coding	protein_coding	ENST00000360566	10	9091

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.745	0.255	125744	0	4	125748	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.34	146	250	0.584	0.0000119	2938
Missense in Polyphen		28	95.848	0.29213		1229
Synonymous	-1.12	106	92.3	1.15	0.00000458	831
Loss of Function	3.56	4	22.1	0.181	0.00000104	258

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000112	0.0000906
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.0000544	0.0000544
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. Inhibits Wnt signaling.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);p53 signaling pathway - 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;Pyrimidine Metabolism;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;UMP Synthase Deiciency (Orotic Aciduria);Gemcitabine Action Pathway;MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy);Molybdenum Cofactor Deficiency;Adenosine Deaminase Deficiency;Gemcitabine Metabolism Pathway;Gout or Kelley-Seegmiller Syndrome;Lesch-Nyhan Syndrome (LNS);Xanthinuria type I;Xanthinuria type II;Beta Ureidopropionase Deficiency;Dihydropyrimidinase Deficiency;Fluoropyrimidine Activity;Mitotic G1-G1-S phases;Retinoblastoma (RB) in Cancer;Hepatitis C and Hepatocellular Carcinoma;Pyrimidine metabolism;Nucleotide Metabolism;pyrimidine deoxyribonucleotides <i>de novo</i> biosynthesis;Gene expression (Transcription);Transcriptional Regulation by E2F6;Generic Transcription Pathway;Metabolism of nucleotides;Interconversion of nucleotide di- and triphosphates;RNA Polymerase II Transcription;Metabolism;Activation of E2F1 target genes at G1/S;G1/S-Specific Transcription;Mitotic G1-G1/S phases;Purine nucleotides nucleosides metabolism;superpathway of purine nucleotide salvage;Pyrimidine nucleotides nucleosides metabolism;G1/S Transition;superpathway of pyrimidine deoxyribonucleotides <i>de novo</i> biosynthesis;pyrimidine deoxyribonucleotides biosynthesis from CTP;guanosine deoxyribonucleotides <i>de novo</i> biosynthesis;Cell Cycle;Cell Cycle, Mitotic;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: 0.216

Intolerance Scores

• loftool: 0.164
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.75

Haploinsufficiency Scores

• pHI: 0.984
• hipred: Y
• hipred_score: 0.825
• ghis: 0.707

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.990

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rrm2
• Phenotype: skeleton 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: rrm2
• Affected structure: trunk
• Phenotype tag: abnormal
• Phenotype quality: necrotic

Gene ontology

• Biological process: regulation of transcription involved in G1/S transition of mitotic cell cycle;DNA replication;deoxyribonucleotide biosynthetic process;oxidation-reduction process;negative regulation of G0 to G1 transition
• Cellular component: cytosol
• Molecular function: ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor;protein binding;metal ion binding