RRM1: Ribonucleotide Reductase Catalytic Subunit M1
A key enzyme in deoxyribonucleotide synthesis, implicated in cancer and genetic disorders.
Gene Information Card
| Symbol | RRM1 |
|---|---|
| Full Name | Ribonucleotide Reductase Catalytic Subunit M1 |
| Gene Type | protein-coding |
| Chromosomal Location | 11p15.4 |
| NCBI Gene ID | 6240 ncbi.nlm.nih.gov/gene/6240 |
| Ensembl ID | ENSG00000167325 |
| UniProt ID | P23921 |
| OMIM ID | 180410 |
| HGNC ID | 10451 |
| Aliases | R1, RR1, ribonucleotide reductase M1 polypeptide |
Description
RRM1 encodes the large catalytic subunit of ribonucleotide reductase, which catalyzes the reduction of ribonucleoside diphosphates to deoxyribonucleoside diphosphates, a rate-limiting step in DNA synthesis. The enzyme is essential for cell proliferation and DNA repair. RRM1 expression is associated with gemcitabine sensitivity in cancer therapy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Non-small cell lung cancer | Elevated RRM1 expression correlates with resistance to gemcitabine-based chemotherapy. | ClinVar, COSMIC |
| Pancreatic cancer | High RRM1 levels predict poor response to gemcitabine. | ClinVar, COSMIC |
| Mitochondrial DNA depletion syndrome 8A (ENMG) | Mutations in RRM1 cause autosomal recessive encephalomyopathic mitochondrial DNA depletion syndrome. | OMIM #612075 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Pancreas | 8.3 | Medium |
| Liver | 6.1 | Low |
| Bone marrow | 15.2 | High |
| Testis | 18.7 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung cancer) | 14.3 | High expression; gemcitabine-resistant lines show further upregulation |
| PANC-1 (pancreatic cancer) | 10.1 | Moderate expression; associated with chemoresistance |
| HEK293 (embryonic kidney) | 7.8 | Baseline expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1130G>A (p.Arg377Gln) | Missense | <0.01% | Reduced enzyme activity; associated with mitochondrial DNA depletion syndrome |
| c.1490C>T (p.Thr497Met) | Missense | <0.01% | Impaired ribonucleotide reductase function; reported in ENMG |
| c.1657G>A (p.Gly553Arg) | Missense | <0.01% | Loss of function; mitochondrial DNA depletion |
Mutation functional classification
Loss of Function (LOF)
Mutations in RRM1 (e.g., p.Arg377Gln, p.Thr497Met) reduce or abolish catalytic activity, leading to impaired dNTP synthesis and mitochondrial DNA depletion.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in RRM1.
Dominant Negative (DN)
Not described for RRM1.
View complete mutation data：
Gene Ontology (GO)
| • ribonucleoside-diphosphate reductase activity | • deoxyribonucleotide biosynthetic process |
| • DNA replication | • DNA repair |
| • nucleotide binding | • iron ion binding |
Pathways
• Purine metabolism
• Pyrimidine metabolism
• DNA replication
• p53 signaling pathway
Protein Summary
RRM1 is the 90 kDa catalytic subunit of ribonucleotide reductase, forming a heterodimer with RRM2. It contains an iron-binding site and a catalytic site that reduces NDPs to dNDPs. The protein is allosterically regulated by ATP and dATP. Overexpression in tumors confers resistance to gemcitabine, a nucleoside analog used in chemotherapy.
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