RRM2B ribonucleotide reductase regulatory TP53 inducible subunit M2B [Homo sapiens (human)] - Gene

Summary

Official Symbol: RRM2Bprovided by HGNC
Official Full Name: ribonucleotide reductase regulatory TP53 inducible subunit M2Bprovided by HGNC
Primary source: HGNC:HGNC:17296
See related: Ensembl:ENSG00000048392 MIM:604712; AllianceGenome:HGNC:17296
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: P53R2; RCDFRD; MTDPS8A; MTDPS8B
Summary: This gene encodes the small subunit of a p53-inducible ribonucleotide reductase. This heterotetrameric enzyme catalyzes the conversion of ribonucleoside diphosphates to deoxyribonucleoside diphosphates. The product of this reaction is necessary for DNA synthesis. Mutations in this gene have been associated with autosomal recessive mitochondrial DNA depletion syndrome, autosomal dominant progressive external ophthalmoplegia-5, and mitochondrial neurogastrointestinal encephalopathy. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2010]
Expression: Ubiquitous expression in thyroid (RPKM 25.9), adrenal (RPKM 13.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 8q22.3

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (102204501..102238961, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (103330401..103364861, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (103216729..103251189, complement)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Impact of N221S missense mutation in human ribonucleotide reductase small subunit b on mitochondrial DNA depletion syndrome.
Title: Impact of N221S missense mutation in human ribonucleotide reductase small subunit b on mitochondrial DNA depletion syndrome.
Identification of two novel RRM2B variants associated with autosomal recessive progressive external ophthalmoplegia in a family with pseudodominant inheritance pattern.
Title: Identification of two novel RRM2B variants associated with autosomal recessive progressive external ophthalmoplegia in a family with pseudodominant inheritance pattern.
Ribonucleotide reductase subunit switching in hepatoblastoma drug response and relapse.
Title: Ribonucleotide reductase subunit switching in hepatoblastoma drug response and relapse.
Clinical, pathological and genetic spectrum in 89 cases of mitochondrial progressive external ophthalmoplegia.
Title: Clinical, pathological and genetic spectrum in 89 cases of mitochondrial progressive external ophthalmoplegia.
The single nucleotide variant at c.662A>G in human RRM2B is a loss-of-function mutation.
Title: The single nucleotide variant at c.662A>G in human RRM2B is a loss-of-function mutation.
Prediction of the Impact of Deleterious Nonsynonymous Single Nucleotide Polymorphisms on the Human RRM2B Gene: A Molecular Modeling Study.
Title: Prediction of the Impact of Deleterious Nonsynonymous Single Nucleotide Polymorphisms on the Human RRM2B Gene: A Molecular Modeling Study.
Infantile-onset mitochondrial DNA depletion syndrome (MDDS) due to RRM2B deficiency is a severe disorder with characteristic clinical features and extremely poor prognosis. The biallelic truncating variants predict the worst survival outcome.
Title: The natural history of infantile mitochondrial DNA depletion syndrome due to RRM2B deficiency.
This report expands our knowledge of potential pathogenic RRM2B mutations as well as our understanding of the molecular function of p53R2 and its role in the pathogenesis of mitochondrial DNA depletion.
Title: A homozygous variant in RRM2B is associated with severe metabolic acidosis and early neonatal death.
Review showed marked variety of clinical manifestations and marked variety of age at onset. Organs predominantly affected in RRM2B mutation carriers are the skeletal muscle, the brain, and the kidneys. Additionally affected may be the eyes, ears, endocrine organs, heart, gastro-intestinal tract, bone marrow, or the peripheral nerves. Phenotype and genotype in RRM2B mutation carriers are more widespread than anticipated.
Title: Phenotypic and Genotypic Heterogeneity of RRM2B Variants.
Our study indicates that the cochlear CHI is a phenotypic feature of the RRM2B and SERAC1 related defects.
Title: Congenital cochlear deafness in mitochondrial diseases related to RRM2B and SERAC1 gene defects. A study of the mitochondrial patients of the CMHI hospital in Warsaw, Poland.

Submit: New GeneRIF Correction See all GeneRIFs (63)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Mitochondrial DNA depletion syndrome 8a MedGen: C2749861 OMIM: 612075 GeneReviews: RRM2B Mitochondrial DNA Maintenance Defects	Compare labs
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5 MedGen: C2751319 OMIM: 613077 GeneReviews: RRM2B Mitochondrial DNA Maintenance Defects	Compare labs
Rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction MedGen: C1849333 OMIM: 268315 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 upregulates the expression of ribonucleotide reductase M2 B (RRM2B) in human B cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in 2'-deoxyribonucleotide biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA repair	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA synthesis involved in DNA repair	NAS Non-traceable Author Statement more info	PubMed
involved_in deoxyribonucleoside triphosphate metabolic process	IEA Inferred from Electronic Annotation more info
involved_in deoxyribonucleotide biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in kidney development	IEA Inferred from Electronic Annotation more info
involved_in mitochondrial DNA replication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of G0 to G1 transition	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of G2/M transition of mitotic cell cycle	IDA Inferred from Direct Assay more info	PubMed
involved_in renal system process	IEA Inferred from Electronic Annotation more info
involved_in response to amine	IEA Inferred from Electronic Annotation more info
involved_in response to oxidative stress	IEA Inferred from Electronic Annotation more info
involved_in ribonucleoside diphosphate metabolic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in mitochondrion	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
part_of ribonucleoside-diphosphate reductase complex	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: ribonucleoside-diphosphate reductase subunit M2 B

Names: TP53-inducible ribonucleotide reductase M2 B; p53-inducible ribonucleotide reductase small subunit 2 homolog; p53-inducible ribonucleotide reductase small subunit 2 short form beta; p53-inducible ribonucleotide reductase small subunit 2-like protein; ribonucleotide reductase M2 B (TP53 inducible)

NP_001165948.1

EC 1.17.4.1

NP_001165949.1

EC 1.17.4.1

NP_056528.2

EC 1.17.4.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016617.1 RefSeqGene

Range

5001..39618

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_788

mRNA and Protein(s)

NM_001172477.1 → NP_001165948.1 ribonucleoside-diphosphate reductase subunit M2 B isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is longer than isoform 1.

Source sequence(s)

AK023605, AK304354, BC108261, DC308409

UniProtKB/TrEMBL

H0YAV1

Related

ENSP00000428115.1, ENST00000522368.5

Conserved Domains (1) summary

cl00264
Location:104 → 423

Ferritin_like; Ferritin-like superfamily of diiron-containing four-helix-bundle proteins
NM_001172478.2 → NP_001165949.1 ribonucleoside-diphosphate reductase subunit M2 B isoform 3

See identical proteins and their annotated locations for NP_001165949.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 3), compared to isoform 1.

Source sequence(s)

AB036063, AK023605, BC108261

Consensus CDS

CCDS55267.1

UniProtKB/TrEMBL

Q6AI41

Related

ENSP00000379248.2, ENST00000395912.6

Conserved Domains (1) summary

cl00264
Location:15 → 299

Ferritin_like; Ferritin-like superfamily of diiron-containing four-helix-bundle proteins
NM_015713.5 → NP_056528.2 ribonucleoside-diphosphate reductase subunit M2 B isoform 1

See identical proteins and their annotated locations for NP_056528.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes isoform 1.

Source sequence(s)

AB036063, AK023605, BC108261

Consensus CDS

CCDS34932.1

UniProtKB/Swiss-Prot

B4E2N4, Q17R22, Q75PQ6, Q75PQ7, Q75PY8, Q75PY9, Q7LG56, Q86YE3, Q9NPD6, Q9NTD8, Q9NUW3

UniProtKB/TrEMBL

Q6AI41

Related

ENSP00000251810.3, ENST00000251810.8

Conserved Domains (1) summary

cl00264
Location:32 → 351

Ferritin_like; Ferritin-like superfamily of diiron-containing four-helix-bundle proteins