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RPP21

gene
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Also known as FLJ22638Em:AB014085.3

Summary

RPP21 (ribonuclease P subunit p21, HGNC:21300) is a protein-coding gene on chromosome 6p22.1, encoding Ribonuclease P protein subunit p21 (Q9H633). Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5’-ends. It is a common-essential gene (DepMap: required in 97.9% of cancer cell lines).

RPP21 is a protein subunit of nuclear ribonuclease P, which processes the 5-prime leader sequence of precursor tRNAs (Jarrous et al., 2001 [PubMed 11497433]).

Source: NCBI Gene 79897 — RefSeq curated summary.

At a glance

  • GWAS associations: 25
  • Clinical variants (ClinVar): 12 total
  • Cancer dependency (DepMap): dependent in 97.9% of screened cell lines (common-essential)
  • MANE Select transcript: NM_024839

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:21300
Approved symbolRPP21
Nameribonuclease P subunit p21
Location6p22.1
Locus typegene with protein product
StatusApproved
AliasesFLJ22638, Em:AB014085.3
Ensembl geneENSG00000241370
Ensembl biotypeprotein_coding
OMIM612524
Entrez79897

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000428040, ENST00000433076, ENST00000436442, ENST00000442966, ENST00000466327, ENST00000473266, ENST00000489124, ENST00000491477, ENST00000498414, ENST00000908531, ENST00000932023, ENST00000932024, ENST00000932025, ENST00000932026, ENST00000932027

RefSeq mRNA: 3 — MANE Select: NM_024839 NM_001199120, NM_001199121, NM_024839

CCDS: CCDS4679, CCDS56409, CCDS56410

Canonical transcript exons

ENST00000376642 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 96.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 44.3780 / max 319.4251, expressed in 1817 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter IDTPM avgSamples expressed
6671835.82081817
667197.36291532
667201.1943790

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
muscle layer of sigmoid colonUBERON:003580596.32gold quality
lower esophagus mucosaUBERON:003583496.22gold quality
lower esophagusUBERON:001347395.86gold quality
lower esophagus muscularis layerUBERON:003583395.86gold quality
putamenUBERON:000187495.63gold quality
nucleus accumbensUBERON:000188295.53gold quality
fundus of stomachUBERON:000116095.50gold quality
caudate nucleusUBERON:000187395.42gold quality
body of uterusUBERON:000985395.39gold quality
esophagusUBERON:000104395.21gold quality
esophagogastric junction muscularis propriaUBERON:003584195.17gold quality
body of stomachUBERON:000116194.98gold quality
esophagus mucosaUBERON:000246994.98gold quality
body of pancreasUBERON:000115094.92gold quality
hypothalamusUBERON:000189894.63gold quality
primary visual cortexUBERON:000243694.61gold quality
amygdalaUBERON:000187694.58gold quality
temporal lobeUBERON:000187194.57gold quality
myometriumUBERON:000129694.54gold quality
mucosa of transverse colonUBERON:000499194.47gold quality
granulocyteCL:000009494.41gold quality
transverse colonUBERON:000115794.41gold quality
colonUBERON:000115594.38gold quality
vaginaUBERON:000099694.22gold quality
anterior cingulate cortexUBERON:000983594.18gold quality
left uterine tubeUBERON:000130394.10gold quality
left coronary arteryUBERON:000162694.10gold quality
Brodmann (1909) area 9UBERON:001354094.08gold quality
popliteal arteryUBERON:000225094.07gold quality
tibial arteryUBERON:000761094.06gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes8.56

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 1)

  • Results demonstrate that Rpp29 and Rpp21 depletion impairs double-strand break (DSB) repair by homology-directed repair (HDR), but has no deleterious effect on the integrity of non-homologous end joining. Rpp29 and Rpp21 are rapidly and transiently recruited to laser-microirradiated sites. They bind poly ADP-ribose moieties and are recruited to DNA damage sites in a PARP1-dependent manner. (PMID:28432356)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriorpp21ENSDARG00000043404
mus_musculusRpp21ENSMUSG00000024446
rattus_norvegicusRpp21ENSRNOG00000000786

Protein

Protein identifiers

Ribonuclease P protein subunit p21 — Q9H633 (reviewed: Q9H633)

Alternative names: Ribonuclease P/MRP 21 kDa subunit, Ribonucleoprotein V

All UniProt accessions (2): A0A1U9X8H3, Q9H633

UniProt curated annotations — full annotation on UniProt →

Function. Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5’-ends.

Subunit / interactions. RNase P consists of a catalytic RNA moiety and about 10 protein subunits; POP1, POP4, POP5, POP7, RPP14, RPP21, RPP25, RPP30, RPP38 and RPP40. Within the RNase P complex, POP1, POP7 and RPP25 form the ‘finger’ subcomplex, POP5, RPP14, RPP40 and homodimeric RPP30 form the ‘palm’ subcomplex, and RPP21, POP4 and RPP38 form the ‘wrist’ subcomplex. All subunits of the RNase P complex interact with the catalytic RNA.

Subcellular location. Nucleus. Nucleolus.

Similarity. Belongs to the eukaryotic/archaeal RNase P protein component 4 family.

Isoforms (4)

UniProt IDNamesCanonical?
Q9H633-11, CAT60-V1yes
Q9H633-22, CAT60-V3
Q9H633-33, CAT60-V4
Q9H633-44

RefSeq proteins (3): NP_001186049, NP_001186050, NP_079115* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR007175Rpr2/Snm1/Rpp21Family

Pfam: PF04032

Enzyme classification (BRENDA):

  • EC 3.1.26.5 — ribonuclease P (BRENDA: 188 organisms, 407 substrates, 80 inhibitors, 54 Km, 43 kcat entries)

Substrate kinetics (BRENDA)

24 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
HUMAN PRE-TRNATYR0.0001–0.00055
PRE-TRNATYR—5
PRE-TRNAASP—4
PTRNATYR0.0002–0.03054
TRNA PRECURSOR—4
PRE-TRNA-TYR0.00012
PRE-TRNATHR(AGT)0.0035–0.052
RNASE P RIBOSWITCH A0.0064–0.00812
TRNAPHE (G+1) PRECURSOR—2
TRNATYR—2
PMINI3PBUG0.00131
PRE-TRNA—1
PRE-TRNA SUPS1 TRNASER0.00021
PRE-TRNA-ASP0.00031
PRE-TRNA-CYS0.00061

UniProt features (16 total): binding site 4, splice variant 3, sequence variant 2, sequence conflict 2, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDBMethodResolution (Å)
6AHUELECTRON MICROSCOPY3.66
6AHRELECTRON MICROSCOPY3.92

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9H633-F182.840.68

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 62; 65; 92; 95

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

IDPathway
R-HSA-6784531tRNA processing in the nucleus
R-HSA-6791226Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-72306tRNA processing
R-HSA-72312rRNA processing
R-HSA-8868773rRNA processing in the nucleus and cytosol
R-HSA-8953854Metabolism of RNA

MSigDB gene sets: 103 (showing top): GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, RACCACAR_AML_Q6, EFC_Q6, GOMF_RNA_ENDONUCLEASE_ACTIVITY, LEF1_Q6, GOBP_TRNA_PROCESSING, REACTOME_METABOLISM_OF_RNA, PARENT_MTOR_SIGNALING_UP, OSF2_Q6, GOCC_NUCLEOLUS

GO Biological Process (4): tRNA 5’-leader removal (GO:0001682), tRNA processing (GO:0008033), response to xenobiotic stimulus (GO:0009410), RNA processing (GO:0006396)

GO Molecular Function (5): ribonuclease P RNA binding (GO:0033204), metal ion binding (GO:0046872), RNA binding (GO:0003723), ribonuclease P activity (GO:0004526), protein binding (GO:0005515)

GO Cellular Component (7): nucleoplasm (GO:0005654), nucleolar ribonuclease P complex (GO:0005655), multimeric ribonuclease P complex (GO:0030681), nucleus (GO:0005634), nucleolus (GO:0005730), endoribonuclease complex (GO:1902555), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-4 pathways:

CategoryPathways
Metabolism of RNA2
tRNA processing1
rRNA processing in the nucleus and cytosol1
rRNA processing1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
nuclear lumen2
tRNA 5’-end processing1
RNA processing1
tRNA metabolic process1
response to chemical1
gene expression1
RNA biosynthetic process1
primary metabolic process1
RNA binding1
cation binding1
nucleic acid binding1
tRNA-specific ribonuclease activity1
RNA endonuclease activity producing 5’-phosphomonoesters, hydrolytic mechanism1
binding1
cellular anatomical structure1
nucleolus1
multimeric ribonuclease P complex1
nuclear protein-containing complex1
ribonuclease P complex1
intracellular membrane-bounded organelle1
intracellular membraneless organelle1
endonuclease complex1
protein-containing complex1

Protein interactions and networks

STRING

726 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
RPP21POP4O95707543
RPP21POP5Q969H6514
RPP21REDIC1Q86WS4480
RPP21C3orf80F5H4A9479
RPP21RPP40O75818479
RPP21TRIM39Q9HCM9475
RPP21RPP30P78346464
RPP21RPP25Q9BUL9411
RPP21TRMT44Q8IYL2409
RPP21MCCD1P59942400
RPP21MRPS24P82668397
RPP21SPMIP5Q8WW14397
RPP21TMEM234Q8WY98392
RPP21RPP38P78345359
RPP21POP1Q99575353
RPP21RPP14O95059353

IntAct

11 interactions, top by confidence:

ABTypeScore
RPP25POP7psi-mi:“MI:0914”(association)0.810
RPP40RPP21psi-mi:“MI:0915”(physical association)0.670
POP4POP7psi-mi:“MI:0914”(association)0.640
RPP21POP7psi-mi:“MI:0914”(association)0.530
RPP30VWA8psi-mi:“MI:0914”(association)0.350
POP5TPP1psi-mi:“MI:0914”(association)0.350
POP7psi-mi:“MI:0915”(physical association)0.320

BioGRID (41): RPP25L (Affinity Capture-MS), RPP25 (Affinity Capture-MS), RPP40 (Affinity Capture-MS), POP7 (Affinity Capture-MS), RPP14 (Affinity Capture-MS), POP4 (Affinity Capture-MS), RPP38 (Affinity Capture-MS), POP1 (Affinity Capture-MS), POP5 (Affinity Capture-MS), RPP30 (Affinity Capture-MS), PSMG3 (Affinity Capture-MS), RPP40 (Reconstituted Complex), RPP21 (Negative Genetic), RPP21 (Phenotypic Suppression), RPP40 (Affinity Capture-MS)

ESM2 similar proteins: A4Q9F4, A6QLH5, A7Z026, B2RYF1, D3ZVU9, O14508, O35652, O35717, O43189, O43414, O54804, O54951, O70512, O88582, P08887, P35790, P85298, Q01134, Q13202, Q29RM4, Q2HJ53, Q3UFK8, Q3UGX3, Q4V892, Q5U2R3, Q5XI70, Q62225, Q68G74, Q6DN14, Q6IA17, Q6P5H6, Q6ZN54, Q7YRV6, Q861R0, Q86W50, Q8BKR5, Q8C460, Q8N5X7, Q8NHH1, Q8TBP0

Diamond homologs: A2BN51, A2STJ3, A3CX01, A4FXV4, A5UL38, A6UNQ2, A6VFL2, A7I9J3, A9AB23, B8GET9, C6A4A4, O27655, O30127, O59248, P62378, Q12VV9, Q2FTK3, Q2NGR3, Q46D07, Q58372, Q5JEC9, Q5TM57, Q8PWM8, Q8R040, Q8TGY1, Q8TTY5, Q8U0H6, Q97C23, Q9H633, Q9V166, Q9YD20, Q9Y813, B0R3R4, C3MJB8, C3MTQ0, C3MZY6, C3N7W8, C3NJ74, C4KJF8, Q4JCL6

SIGNOR signaling

1 interactions.

AEffectBMechanism
RPP21“form complex”“Nucleolar ribonuclease P complex”binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

12 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance8
Likely benign3
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

422 predictions. Top by Δscore:

VariantEffectΔscore
6:30345227:AGGTG:Adonor_loss1.0000
6:30345229:G:GAdonor_loss1.0000
6:30345230:T:Gdonor_loss1.0000
6:30345569:GAGAC:Gdonor_gain1.0000
6:30345571:GAC:Gdonor_gain1.0000
6:30345229:G:GGdonor_gain0.9900
6:30345395:GGCG:Gdonor_gain0.9900
6:30345396:GCG:Gdonor_gain0.9900
6:30345396:GCGG:Gdonor_gain0.9900
6:30345399:G:GGdonor_gain0.9900
6:30345574:G:GGdonor_gain0.9900
6:30345593:TGG:Tdonor_gain0.9900
6:30345397:CGGT:Cdonor_loss0.9800
6:30345398:GGTG:Gdonor_loss0.9800
6:30345399:GTGA:Gdonor_loss0.9800
6:30345400:T:Cdonor_loss0.9800
6:30345485:CCCCA:Cacceptor_loss0.9800
6:30345486:CCCA:Cacceptor_loss0.9800
6:30345487:CCA:Cacceptor_loss0.9800
6:30345488:CAGG:Cacceptor_loss0.9800
6:30345489:A:AGacceptor_gain0.9800
6:30345489:A:ATacceptor_loss0.9800
6:30345489:AG:Aacceptor_gain0.9800
6:30345489:AGG:Aacceptor_gain0.9800
6:30345490:G:Aacceptor_loss0.9800
6:30345490:G:GGacceptor_gain0.9800
6:30345490:GG:Gacceptor_gain0.9800
6:30345490:GGG:Gacceptor_gain0.9800
6:30345573:CG:Cdonor_loss0.9800
6:30345574:GTGA:Gdonor_loss0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000849666 (6:30343376 T>G), RS1001659756 (6:30344072 G>A), RS1002989312 (6:30346033 A>G), RS1003345190 (6:30343849 C>T), RS1003822 (6:30345104 C>T), RS1004993843 (6:30343447 A>G), RS1005979591 (6:30346503 C>G), RS1006406898 (6:30344800 C>T), RS1006727586 (6:30347182 C>G), RS1010699757 (6:30344311 C>T), RS1011082991 (6:30345042 G>T), RS1013203448 (6:30346341 G>A), RS1013336522 (6:30345966 G>T), RS1013928299 (6:30344516 G>GA), RS1014625979 (6:30344920 T>A)

Disease associations

OMIM: gene MIM:612524 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

25 associations (top):

StudyTraitp-value
GCST002884_2Cutaneous lupus erythematosus2.000000e-11
GCST002884_4Cutaneous lupus erythematosus2.000000e-11
GCST004521_114Autism spectrum disorder or schizophrenia3.000000e-17
GCST004521_121Autism spectrum disorder or schizophrenia3.000000e-13
GCST004521_132Autism spectrum disorder or schizophrenia2.000000e-09
GCST004521_171Autism spectrum disorder or schizophrenia4.000000e-14
GCST004521_2Autism spectrum disorder or schizophrenia2.000000e-16
GCST004521_210Autism spectrum disorder or schizophrenia5.000000e-15
GCST004521_263Autism spectrum disorder or schizophrenia7.000000e-17
GCST004521_265Autism spectrum disorder or schizophrenia7.000000e-14
GCST004521_268Autism spectrum disorder or schizophrenia7.000000e-12
GCST004521_269Autism spectrum disorder or schizophrenia7.000000e-11
GCST004521_295Autism spectrum disorder or schizophrenia6.000000e-18
GCST004521_3Autism spectrum disorder or schizophrenia2.000000e-15
GCST004521_44Autism spectrum disorder or schizophrenia2.000000e-17
GCST004521_56Autism spectrum disorder or schizophrenia1.000000e-22
GCST004521_70Autism spectrum disorder or schizophrenia8.000000e-20
GCST004521_79Autism spectrum disorder or schizophrenia1.000000e-16
GCST005232_23Neuroticism8.000000e-09
GCST005541_12Sarcoidosis (Lofgren’s syndrome vs non-Lofgren’s syndrome)4.000000e-23
GCST006097_5Moderate to vigorous physical activity levels1.000000e-09
GCST006940_74Neurociticism7.000000e-10
GCST011656_10Lung cancer3.000000e-10
GCST011773_4Type 1 diabetes (age at diagnosis)1.000000e-06
GCST012354_18Anxiety1.000000e-12

EFO canonical traits (4, from GWAS)

EFO IDTrait name
EFO:0007660neuroticism measurement
EFO:0008002physical activity measurement
EFO:0004918age at diagnosis
EFO:0009863anxiety measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects cotreatment, increases expression, affects expression2
Cyclosporineincreases expression2
methylmercuric chlorideincreases expression1
bisphenol Aaffects expression1
sodium arseniteincreases expression, affects cotreatment, increases abundance1
manganese chlorideaffects cotreatment, increases abundance, increases expression1
metolachlorincreases abundance, affects methylation1
CGP 52608increases reaction, affects binding1
2-palmitoylglycerolincreases expression1
ICG 001increases expression1
bisphenol Sdecreases methylation1
Temozolomideincreases expression1
Arsenicaffects cotreatment, increases abundance, increases expression1
Azacitidineincreases expression1
Benzo(a)pyreneaffects methylation1
Herbicidesincreases abundance, affects methylation1
Hydralazineincreases expression, affects cotreatment1
Manganeseaffects cotreatment, increases abundance, increases expression1
Smokedecreases expression1
T-2 Toxinincreases expression1
Xylitoldecreases expression1
Copper Sulfateincreases expression1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): cutaneous lupus erythematosus, sarcoidosis

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 75

This page pulls from 75 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot