RRM2B

Chr 8ARAD

ribonucleotide reductase regulatory TP53 inducible subunit M2B

Also known as: MTDPS8A, MTDPS8B, P53R2, RCDFRD

The protein encodes the small subunit of ribonucleotide reductase, which catalyzes the conversion of ribonucleoside diphosphates to deoxyribonucleoside diphosphates necessary for DNA synthesis. Mutations cause mitochondrial DNA depletion syndromes (encephalomyopathic type with renal tubulopathy and MNGIE type) and rod-cone dystrophy with sensorineural deafness and Fanconi-type renal dysfunction through autosomal recessive inheritance, or progressive external ophthalmoplegia with mitochondrial DNA deletions through autosomal dominant inheritance. The pathogenic mechanism involves dominant-negative effects disrupting mitochondrial DNA maintenance.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismAR/ADLOEUF 0.704 OMIM phenotypes
Clinical SummaryRRM2B
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.70LOEUF
pLI 0.002
Z-score 2.58
OE 0.39 (0.230.70)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.21Z-score
OE missense 0.75 (0.650.86)
137 obs / 182.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.39 (0.230.70)
00.351.4
Missense OE0.75 (0.650.86)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 8 / 20.7Missense obs/exp: 137 / 182.9Syn Z: 0.84
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveRRM2B-related mitochondrial depletion syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.82top 10%
GOF
0.76top 25%
LOF
0.1895th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNWe conclude that dominant-negative or gain-of-function mutations in RRM2B are a cause of multiple mtDNA deletions and adPEO.PMID:19664747
GOFWe conclude that dominant-negative or gain-of-function mutations in RRM2B are a cause of multiple mtDNA deletions and adPEO.PMID:19664747

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RRM2B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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