RPP38

Summary

RPP38 (ribonuclease P/MRP subunit p38, HGNC:30329) is a protein-coding gene on chromosome 10p13, encoding Ribonuclease P protein subunit p38 (P78345). Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5’-ends. It is a selective cancer dependency (DepMap: 72.6% of cell lines).

Enables ribonuclease P RNA binding activity. Contributes to ribonuclease P activity. Involved in tRNA 5’-leader removal. Located in fibrillar center. Part of multimeric ribonuclease P complex.

Source: NCBI Gene 10557 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 47 total
• Cancer dependency (DepMap): dependent in 72.6% of screened cell lines
• MANE Select transcript: NM_183005

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30329
Approved symbol	RPP38
Name	ribonuclease P/MRP subunit p38
Location	10p13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000152464
Ensembl biotype	protein_coding
OMIM	606116
Entrez	10557

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 19 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000378197, ENST00000378201, ENST00000378202, ENST00000378203, ENST00000441850, ENST00000451677, ENST00000616640, ENST00000890835, ENST00000890836, ENST00000890837, ENST00000890838, ENST00000890839, ENST00000890840, ENST00000890841, ENST00000890842, ENST00000890843, ENST00000924142, ENST00000924143, ENST00000924144, ENST00000924145

RefSeq mRNA: 4 — MANE Select: NM_183005 NM_001097590, NM_001265601, NM_006414, NM_183005

CCDS: CCDS7108

Canonical transcript exons

ENST00000378197 — 3 exons

Exon	Start	End
ENSE00001476617	15097355	15097766
ENSE00001476631	15102218	15102336
ENSE00001931579	15103305	15104257

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 93.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.7771 / max 110.7990, expressed in 1811 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103999	15.0652	1803
103998	1.8957	1138
104000	0.6707	417
103997	0.5835	303
104002	0.5316	121
104001	0.0304	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	93.06	gold quality
right testis	UBERON:0004534	92.84	gold quality
testis	UBERON:0000473	91.89	gold quality
bronchial epithelial cell	CL:0002328	91.75	gold quality
epithelium of bronchus	UBERON:0002031	91.36	gold quality
bronchus	UBERON:0002185	90.78	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.18	gold quality
right uterine tube	UBERON:0001302	89.35	gold quality
mucosa of transverse colon	UBERON:0004991	88.32	gold quality
sperm	CL:0000019	88.29	gold quality
male germ cell	CL:0000015	88.27	gold quality
nasal cavity epithelium	UBERON:0005384	87.71	gold quality
oocyte	CL:0000023	87.64	gold quality
granulocyte	CL:0000094	87.61	gold quality
rectum	UBERON:0001052	87.59	gold quality
islet of Langerhans	UBERON:0000006	87.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.49	gold quality
cerebellar hemisphere	UBERON:0002245	86.97	gold quality
cerebellar cortex	UBERON:0002129	86.80	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.45	gold quality
epithelium of nasopharynx	UBERON:0001951	86.31	gold quality
gastrocnemius	UBERON:0001388	86.27	gold quality
cervix squamous epithelium	UBERON:0006922	86.10	silver quality
mucosa of paranasal sinus	UBERON:0005030	85.67	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.66	gold quality
muscle of leg	UBERON:0001383	85.64	gold quality
lower esophagus	UBERON:0013473	85.64	gold quality
transverse colon	UBERON:0001157	85.62	gold quality
adult organism	UBERON:0007023	85.37	gold quality
lymph node	UBERON:0000029	85.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.42

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 72.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• A pull-down assay further suggested the presence of a second K-turn in SL12. Based on the present results, together with available data, we discuss a structural basis for recognition of K-turn motifs in PhopRNA by PhoRpp38. (PMID:27114305)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpp38	ENSDARG00000040350
mus_musculus	Rpp38	ENSMUSG00000049950
rattus_norvegicus	Rpp38	ENSRNOG00000063181

Protein

Protein identifiers

Ribonuclease P protein subunit p38 — P78345 (reviewed: P78345)

All UniProt accessions (3): P78345, Q5VUC3, Q5VUC9

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. Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences.

Subunit / interactions. Component of nuclear RNase P and RNase MRP ribonucleoproteins. 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. Several subunits of RNase P are also part of the RNase MRP complex. RNase MRP consists of a catalytic RNA moiety and about 8 protein subunits; POP1, POP7, RPP25, RPP30, RPP38, RPP40 and possibly also POP4 and POP5.

Subcellular location. Nucleus. Nucleolus.

Miscellaneous. Autoantibodies against RPP38 are found in sera from scleroderma patients.

Similarity. Belongs to the eukaryotic ribosomal protein eL8 family.

RefSeq proteins (4): NP_001091059, NP_001252530, NP_006405, NP_892117* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004038	Ribosomal_eL8/eL30/eS12/Gad45	Domain
IPR029064	Ribosomal_eL30-like_sf	Homologous_superfamily
IPR042848	Rpp38	Family

Pfam: PF01248

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.

Substrate	Km (mM)	Measurements
HUMAN PRE-TRNATYR	0.0001–0.0005	5
PRE-TRNATYR	—	5
PRE-TRNAASP	—	4
PTRNATYR	0.0002–0.0305	4
TRNA PRECURSOR	—	4
PRE-TRNA-TYR	0.0001	2
PRE-TRNATHR(AGT)	0.0035–0.05	2
RNASE P RIBOSWITCH A	0.0064–0.0081	2
TRNAPHE (G+1) PRECURSOR	—	2
TRNATYR	—	2
PMINI3PBUG	0.0013	1
PRE-TRNA	—	1
PRE-TRNA SUPS1 TRNASER	0.0002	1
PRE-TRNA-ASP	0.0003	1
PRE-TRNA-CYS	0.0006	1

UniProt features (14 total): sequence variant 7, modified residue 4, initiator methionine 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9UH9	ELECTRON MICROSCOPY	3.47
6AHU	ELECTRON MICROSCOPY	3.66
6AHR	ELECTRON MICROSCOPY	3.92
9UHA	ELECTRON MICROSCOPY	3.93

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78345-F1	72.79	0.45

Functional residue map

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

Post-translational modifications (4): 2, 12, 226, 235

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

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

MSigDB gene sets: 94 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, TGCGCANK_UNKNOWN, MORF_RAB5A, GOMF_NUCLEASE_ACTIVITY, GOBP_TRNA_METABOLIC_PROCESS, MEF2_02, RIZKI_TUMOR_INVASIVENESS_3D_DN, MORF_PSMC2, chr10p13, GOMF_RNA_ENDONUCLEASE_ACTIVITY, PETRETTO_HEART_MASS_QTL_CIS_DN, MORF_PPP6C, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS

GO Biological Process (3): tRNA 5’-leader removal (GO:0001682), rRNA processing (GO:0006364), tRNA processing (GO:0008033)

GO Molecular Function (4): ribonuclease P RNA binding (GO:0033204), RNA binding (GO:0003723), ribonuclease P activity (GO:0004526), protein binding (GO:0005515)

GO Cellular Component (7): ribonuclease MRP complex (GO:0000172), fibrillar center (GO:0001650), nucleoplasm (GO:0005654), nucleolar ribonuclease P complex (GO:0005655), nucleolus (GO:0005730), multimeric ribonuclease P complex (GO:0030681), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Metabolism of RNA	2
tRNA processing	1
rRNA processing in the nucleus and cytosol	1
rRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
nucleolus	2
cellular anatomical structure	2
nuclear lumen	2
tRNA 5’-end processing	1
rRNA metabolic process	1
ribosome biogenesis	1
tRNA metabolic process	1
RNA binding	1
nucleic acid binding	1
tRNA-specific ribonuclease activity	1
RNA endonuclease activity producing 5’-phosphomonoesters, hydrolytic mechanism	1
binding	1
sno(s)RNA-containing ribonucleoprotein complex	1
endoribonuclease complex	1
multimeric ribonuclease P complex	1
nuclear protein-containing complex	1
intracellular membraneless organelle	1
ribonuclease P complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3886 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPP38	RPP25	Q9BUL9	998
RPP38	RPP30	P78346	998
RPP38	POP4	O95707	998
RPP38	RPP40	O75818	996
RPP38	POP5	Q969H6	986
RPP38	POP7	O75817	582
RPP38	UTP15	Q8TED0	489
RPP38	POP1	Q99575	479
RPP38	ZNF611	Q8N823	465
RPP38	NXPE3	Q969Y0	461
RPP38	TBCEL	Q5QJ74	449
RPP38	HTD2	P86397	443
RPP38	RPLP1	P05386	440
RPP38	WDR75	Q8IWA0	425
RPP38	B3GALNT1	O75752	423

IntAct

103 interactions, top by confidence:

A	B	Type	Score
NOP10	DKC1	psi-mi:“MI:0914”(association)	0.890
RPP25	POP7	psi-mi:“MI:0914”(association)	0.810
RPP38	POP4	psi-mi:“MI:0915”(physical association)	0.740
POP4	RPP38	psi-mi:“MI:0915”(physical association)	0.740
RPP30	POP7	psi-mi:“MI:0914”(association)	0.730
IFT27	IFT56	psi-mi:“MI:0914”(association)	0.690
RPP14	RPP40	psi-mi:“MI:0914”(association)	0.670
C18orf21	POP7	psi-mi:“MI:0914”(association)	0.640
POP4	POP7	psi-mi:“MI:0914”(association)	0.640
NPM1	NVL	psi-mi:“MI:0914”(association)	0.610
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
ING4	KAT7	psi-mi:“MI:0914”(association)	0.530
TOR1AIP2	TMEM223	psi-mi:“MI:0914”(association)	0.530
POP4	NME2P1	psi-mi:“MI:0914”(association)	0.530
RPP21	POP7	psi-mi:“MI:0914”(association)	0.530
POP7	RPP40	psi-mi:“MI:0914”(association)	0.530
RPP25L	RPP40	psi-mi:“MI:0914”(association)	0.530
C18orf21	RPP40	psi-mi:“MI:0914”(association)	0.530
RPP30	RPP38	psi-mi:“MI:0914”(association)	0.530
RPP30	RPP40	psi-mi:“MI:0914”(association)	0.530
POP4	RPP40	psi-mi:“MI:0914”(association)	0.530
RPP14	POP7	psi-mi:“MI:0914”(association)	0.530
SRSF3	CASC3	psi-mi:“MI:0914”(association)	0.530
ABL1	RPP38	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (129): RPP38 (Affinity Capture-MS), RPP38 (Affinity Capture-MS), RPP38 (Affinity Capture-MS), RPP38 (Affinity Capture-MS), RPP38 (Affinity Capture-MS), RPP38 (Affinity Capture-MS), RPP38 (Affinity Capture-MS), RPP38 (Affinity Capture-MS), RPP38 (Affinity Capture-MS), RPP38 (Affinity Capture-MS), RPP38 (Proximity Label-MS), RPP38 (Affinity Capture-MS), RPP38 (Affinity Capture-MS), RPP38 (Affinity Capture-MS), RPP38 (Affinity Capture-MS)

ESM2 similar proteins: A4FV97, A6NFN9, F6RRD7, O60934, O96028, P14629, P38432, P78345, Q05CL8, Q12789, Q28G87, Q32LC1, Q3MHN7, Q3U3S3, Q3US16, Q496Z9, Q4AC94, Q4G0J3, Q4R627, Q52KB6, Q561R3, Q5EA18, Q5I0E6, Q5R5T0, Q5RA37, Q5RCV3, Q5RL73, Q63505, Q7Z2T5, Q7ZWE3, Q80UU2, Q8BMI4, Q8BVY0, Q8C6C7, Q8IXW5, Q8K284, Q8K2X2, Q8N0S6, Q8N8B7, Q8VC34

Diamond homologs: O26355, P78345, Q32LC1, Q80UU2, Q8TV03

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
RPP38	“form complex”	“Ribonuclease MRP complex”	binding
RPP38	“form complex”	“Nucleolar ribonuclease P complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 114 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
tRNA processing	6	28.2×	1e-05
tRNA processing in the nucleus	10	25.9×	2e-09
rRNA processing in the nucleus and cytosol	7	14.8×	7e-05
FCGR3A-mediated phagocytosis	6	14.8×	3e-04
rRNA processing	7	13.5×	1e-04
Signaling by ROBO receptors	6	9.8×	2e-03
Transcriptional regulation by RUNX1	5	9.6×	9e-03
mRNA Polyadenylation	7	8.1×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
tRNA processing	5	43.9×	2e-05
ephrin receptor signaling pathway	5	17.9×	2e-03
rRNA processing	10	14.8×	6e-07
regulation of alternative mRNA splicing, via spliceosome	5	12.7×	8e-03
ribosomal small subunit biogenesis	5	11.9×	8e-03
RNA processing	5	11.4×	8e-03
RNA splicing	7	6.4×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2025 predictions. Top by Δscore:

Variant	Effect	Δscore
10:15103288:ATTTT:A	acceptor_gain	1.0000
10:15103292:T:A	acceptor_gain	1.0000
10:15109697:CTTA:C	donor_loss	1.0000
10:15109698:TTA:T	donor_loss	1.0000
10:15109700:A:AC	donor_gain	1.0000
10:15109701:C:CC	donor_gain	1.0000
10:15109701:C:CT	donor_loss	1.0000
10:15109836:CTTT:C	acceptor_gain	1.0000
10:15109838:TT:T	acceptor_gain	1.0000
10:15109840:C:CC	acceptor_gain	1.0000
10:15109840:C:T	acceptor_loss	1.0000
10:15109844:C:CT	acceptor_gain	1.0000
10:15109844:C:T	acceptor_gain	1.0000
10:15109845:A:T	acceptor_gain	1.0000
10:15109846:A:AC	acceptor_gain	1.0000
10:15109846:A:C	acceptor_gain	1.0000
10:15109847:T:C	acceptor_gain	1.0000
10:15109847:T:TC	acceptor_gain	1.0000
10:15109848:T:C	acceptor_gain	1.0000
10:15109848:T:TC	acceptor_gain	1.0000
10:15112645:T:C	donor_gain	1.0000
10:15112790:GCTTA:G	donor_loss	1.0000
10:15112791:CTTAC:C	donor_loss	1.0000
10:15112792:TTA:T	donor_loss	1.0000
10:15112793:TACCG:T	donor_loss	1.0000
10:15112794:A:AC	donor_gain	1.0000
10:15112794:A:T	donor_loss	1.0000
10:15112794:AC:A	donor_gain	1.0000
10:15112795:C:CA	donor_gain	1.0000
10:15112795:CC:C	donor_gain	1.0000

AlphaMissense

1844 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:15103411:T:A	W33R	0.994
10:15103411:T:C	W33R	0.994
10:15103765:A:C	S151R	0.988
10:15103767:C:A	S151R	0.988
10:15103767:C:G	S151R	0.988
10:15103413:G:C	W33C	0.985
10:15103413:G:T	W33C	0.985
10:15103624:T:A	W104R	0.981
10:15103624:T:C	W104R	0.981
10:15103933:T:A	W207R	0.981
10:15103933:T:C	W207R	0.981
10:15103856:C:A	A181E	0.978
10:15103787:C:A	A158D	0.970
10:15103644:G:C	R110S	0.967
10:15103644:G:T	R110S	0.967
10:15103626:G:C	W104C	0.965
10:15103626:G:T	W104C	0.965
10:15103820:C:A	A169D	0.965
10:15103859:T:C	F182S	0.963
10:15103807:A:C	S165R	0.962
10:15103809:T:A	S165R	0.962
10:15103809:T:G	S165R	0.962
10:15103771:A:C	S153R	0.961
10:15103773:C:A	S153R	0.961
10:15103773:C:G	S153R	0.961
10:15103850:C:A	A179D	0.961
10:15104090:T:A	L259H	0.960
10:15103689:A:C	E125D	0.959
10:15103689:A:T	E125D	0.959
10:15103412:G:C	W33S	0.956

dbSNP variants (sampled 300 via entrez): RS1000201203 (10:15099422 A>C,G), RS1000339820 (10:15098515 C>T), RS1000519149 (10:15100822 G>A), RS1001050133 (10:15096250 C>A), RS1001517404 (10:15104558 G>A), RS1001609458 (10:15097538 G>A), RS1001988785 (10:15101781 T>C), RS1002235080 (10:15095883 T>C), RS1002341531 (10:15097031 G>A), RS1002755690 (10:15100611 T>C), RS1003047091 (10:15097656 C>T), RS1003351624 (10:15099344 T>G), RS1003425837 (10:15097913 A>T), RS1003504441 (10:15100533 G>T), RS1003611375 (10:15095853 T>C)

Disease associations

OMIM: gene MIM:606116 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002595_16	Clozapine-induced agranulocytosis	5.000000e-06
GCST008359_6	Response to cognitive-behavioural therapy in anxiety disorder	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy

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.

Chemical	Actions (top 5)	PubMed papers
Smoke	decreases expression, increases abundance	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
picoxystrobin	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Coal	decreases expression, increases abundance	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Quercetin	decreases expression	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Thiram	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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