RPP25L

Summary

RPP25L (ribonuclease P/MRP subunit p25 like, HGNC:19909) is a protein-coding gene on chromosome 9p13.3, encoding Ribonuclease P protein subunit p25-like protein (Q8N5L8). May be a component of ribonuclease P or MRP. It is a selective cancer dependency (DepMap: 32.4% of cell lines).

This gene encodes a protein that appears to belong to a family of evolutionarily related proteins (DUF78), that may share one or more domains in common. Members of this family are small archaebacterial proteins with no known function. Alternative splicing has been observed at this locus and two variants, both encoding the same protein, have been identified.

Source: NCBI Gene 138716 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 22 total
• Cancer dependency (DepMap): dependent in 32.4% of screened cell lines
• MANE Select transcript: NM_148178

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19909
Approved symbol	RPP25L
Name	ribonuclease P/MRP subunit p25 like
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	bA296L22.5, MGC29635
Ensembl gene	ENSG00000164967
Ensembl biotype	protein_coding
Entrez	138716

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000297613, ENST00000378959, ENST00000923013, ENST00000923014

RefSeq mRNA: 2 — MANE Select: NM_148178 NM_148178, NM_148179

CCDS: CCDS6559

Canonical transcript exons

ENST00000378959 — 2 exons

Exon	Start	End
ENSE00001479396	34612064	34612097
ENSE00003847077	34610495	34611332

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 96.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.6321 / max 75.1101, expressed in 1800 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100526	13.6321	1800

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	96.61	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.04	gold quality
gastrocnemius	UBERON:0001388	96.00	gold quality
deltoid	UBERON:0001476	95.92	gold quality
quadriceps femoris	UBERON:0001377	95.62	gold quality
left ventricle myocardium	UBERON:0006566	95.61	gold quality
muscle of leg	UBERON:0001383	95.46	gold quality
vastus lateralis	UBERON:0001379	95.22	gold quality
apex of heart	UBERON:0002098	94.93	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.82	silver quality
ileal mucosa	UBERON:0000331	94.78	gold quality
pancreatic ductal cell	CL:0002079	94.60	silver quality
skeletal muscle tissue	UBERON:0001134	94.60	gold quality
mucosa of transverse colon	UBERON:0004991	94.40	gold quality
biceps brachii	UBERON:0001507	94.12	gold quality
myocardium	UBERON:0002349	93.88	silver quality
endothelial cell	CL:0000115	93.68	gold quality
muscle tissue	UBERON:0002385	93.67	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.59	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.41	gold quality
body of tongue	UBERON:0011876	92.02	gold quality
heart left ventricle	UBERON:0002084	91.71	gold quality
right lobe of liver	UBERON:0001114	91.66	gold quality
cardiac ventricle	UBERON:0002082	91.60	gold quality
upper arm skin	UBERON:0004263	91.57	gold quality
kidney epithelium	UBERON:0004819	91.18	silver quality
heart	UBERON:0000948	89.82	gold quality
gingival epithelium	UBERON:0001949	89.80	gold quality
lateral globus pallidus	UBERON:0002476	89.78	gold quality
cardiac atrium	UBERON:0002081	89.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting RPP25L, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-129-1-3P	98.86	68.41	779
HSA-MIR-129-2-3P	98.86	68.41	779
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-6831-5P	98.26	67.20	990
HSA-MIR-3927-3P	97.68	66.76	892
HSA-MIR-938	97.41	68.28	656
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-215-3P	97.02	68.01	1209
HSA-MIR-549A-5P	96.35	68.08	587
HSA-MIR-1538	85.86	60.08	75
HSA-MIR-4745-3P	83.50	60.58	126

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 32.4% of screened cell lines.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpp25l	ENSDARG00000070131
mus_musculus	Rpp25l	ENSMUSG00000036114
rattus_norvegicus	Rpp25l	ENSRNOG00000064027
drosophila_melanogaster	Rpp25	FBGN0033092
caenorhabditis_elegans		WBGENE00014020

Paralogs (1): RPP25 (ENSG00000178718)

Protein

Protein identifiers

Ribonuclease P protein subunit p25-like protein — Q8N5L8 (reviewed: Q8N5L8)

Alternative names: Rpp25-like protein

All UniProt accessions (1): Q8N5L8

UniProt curated annotations — full annotation on UniProt →

Function. May be a component of ribonuclease P or MRP.

Subcellular location. Nucleus.

Similarity. Belongs to the histone-like Alba family.

RefSeq proteins (2): NP_680544, NP_680545 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002775	DNA/RNA-bd_Alba-like	Domain
IPR036882	Alba-like_dom_sf	Homologous_superfamily
IPR051958	Alba-like_NAB	Family

Pfam: PF01918

UniProt features (5 total): region of interest 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N5L8-F1	88.11	0.77

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 86 (showing top): GOBP_TRNA_METABOLIC_PROCESS, RACCACAR_AML_Q6, TGACCTY_ERR1_Q2, YY1_Q6, CCANNAGRKGGC_UNKNOWN, chr9p13, HAMAI_APOPTOSIS_VIA_TRAIL_DN, GOBP_TRNA_PROCESSING, GCCATNTTG_YY1_Q6, NUYTTEN_EZH2_TARGETS_DN, GOCC_SNO_S_RNA_CONTAINING_RIBONUCLEOPROTEIN_COMPLEX, GOCC_RIBONUCLEOPROTEIN_COMPLEX, TCANNTGAY_SREBP1_01, GOBP_RNA_5_END_PROCESSING, GOBP_TRNA_5_LEADER_REMOVAL

GO Biological Process (1): tRNA 5’-leader removal (GO:0001682)

GO Molecular Function (3): RNA binding (GO:0003723), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (2): ribonuclease MRP complex (GO:0000172), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
tRNA 5’-end processing	1
nucleic acid binding	1
sno(s)RNA-containing ribonucleoprotein complex	1
endoribonuclease complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

706 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPP25L	FAM219A	Q8IW50	654
RPP25L	DCTN3	O75935	609
RPP25L	POP5	Q969H6	534
RPP25L	FAM50A	Q14320	532
RPP25L	ENHO	Q6UWT2	527
RPP25L	FAM50B	Q9Y247	495
RPP25L	UBR4	Q5T4S7	489
RPP25L	PPIP5K2	O43314	486
RPP25L	C7orf57	Q8NEG2	472
RPP25L	SPMIP6	Q8NCR6	446
RPP25L	AATF	Q9NY61	446
RPP25L	PWP2	Q15269	443
RPP25L	TUBA4A	P05215	442
RPP25L	SPATA31F1	Q6ZU69	434
RPP25L	POP7	O75817	432

IntAct

95 interactions, top by confidence:

A	B	Type	Score
RPP25L	POP7	psi-mi:“MI:0915”(physical association)	0.870
RPP25L	ARHGEF2	psi-mi:“MI:0915”(physical association)	0.870
POP7	RPP25L	psi-mi:“MI:0915”(physical association)	0.870
ARHGEF2	RPP25L	psi-mi:“MI:0915”(physical association)	0.870
RPP30	POP7	psi-mi:“MI:0914”(association)	0.730
RPP25L	KLHL12	psi-mi:“MI:0915”(physical association)	0.720
KLHL12	RPP25L	psi-mi:“MI:0915”(physical association)	0.720
PLK1	EVI5	psi-mi:“MI:0914”(association)	0.660
C18orf21	POP7	psi-mi:“MI:0914”(association)	0.640
POP4	POP7	psi-mi:“MI:0914”(association)	0.640
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
RPP25L	PNMA1	psi-mi:“MI:0915”(physical association)	0.560
RPGRIP1	RPP25L	psi-mi:“MI:0915”(physical association)	0.560
RPP25L	MID2	psi-mi:“MI:0915”(physical association)	0.560
PNMA1	RPP25L	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (104): RPP25L (Two-hybrid), RPP25L (Two-hybrid), RPP25L (Two-hybrid), RPP25L (Two-hybrid), RPP25L (Two-hybrid), RPP25L (Two-hybrid), RPP25L (Affinity Capture-MS), RPP25L (Affinity Capture-MS), RPP25L (Affinity Capture-MS), RPP25L (Synthetic Lethality), RPP25L (Affinity Capture-MS), RPP25L (Affinity Capture-MS), RPP25L (Affinity Capture-MS), RPP25L (Affinity Capture-MS), RPP25L (Affinity Capture-MS)

ESM2 similar proteins: E2RDP2, O14526, O14558, O15197, O35878, O95382, P02512, P04792, P0C0K6, P0C5W1, P14602, P15991, P42929, P42930, P97541, Q00649, Q08DM2, Q13470, Q148F8, Q16082, Q2KHU9, Q2KIR4, Q3T033, Q3T149, Q4VYA0, Q5EBG6, Q5JR98, Q5JZY3, Q5RE82, Q5S1U1, Q6F5E8, Q6NY19, Q6P9Q4, Q6SJQ8, Q6ZW31, Q8C052, Q8CDY7, Q8N5L8, Q8TBH0, Q8TDZ2

Diamond homologs: Q2KIR4, Q5PPN2, Q8IAX8, Q8N5L8, Q91WE3, Q99JH1, Q9BUL9, Q8IDN4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 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	5	36.4×	8e-06
tRNA processing in the nucleus	7	28.1×	2e-07
rRNA processing in the nucleus and cytosol	8	26.3×	1e-07
rRNA processing	8	23.9×	1e-07
Major pathway of rRNA processing in the nucleolus and cytosol	10	12.6×	2e-07
Metabolism of RNA	11	9.4×	7e-07

GO biological processes:

GO term	Partners	Fold	FDR
rRNA processing	9	19.3×	2e-07
ribosomal small subunit biogenesis	5	17.2×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

216 predictions. Top by Δscore:

Variant	Effect	Δscore
9:34611890:CAGAA:C	donor_gain	0.9900
9:34611891:AGAAA:A	donor_gain	0.9900
9:34611937:T:A	donor_gain	0.9900
9:34611333:C:CC	acceptor_gain	0.9800
9:34611887:A:AC	donor_gain	0.9800
9:34611888:C:CC	donor_gain	0.9800
9:34611891:A:AC	donor_gain	0.9800
9:34611892:G:C	donor_gain	0.9800
9:34611929:CAGG:C	donor_gain	0.9800
9:34611930:AGGA:A	donor_gain	0.9800
9:34611329:CCCA:C	acceptor_gain	0.9700
9:34611330:CCAC:C	acceptor_gain	0.9700
9:34611331:CA:C	acceptor_gain	0.9700
9:34611330:CCA:C	acceptor_gain	0.9500
9:34611331:CAC:C	acceptor_gain	0.9500
9:34611875:T:C	donor_gain	0.9300
9:34611877:A:AT	donor_gain	0.9300
9:34611912:CG:C	donor_gain	0.9300
9:34611884:G:GC	donor_gain	0.9200
9:34611913:G:GT	donor_gain	0.9200
9:34612062:A:AC	donor_gain	0.9100
9:34612063:C:CC	donor_gain	0.9100
9:34611332:AC:A	acceptor_loss	0.8700
9:34611334:T:G	acceptor_loss	0.8700
9:34611946:G:GA	donor_gain	0.8700
9:34611976:T:TA	donor_gain	0.8600
9:34612057:CTCT:C	donor_loss	0.8600
9:34612058:TCTCA:T	donor_loss	0.8600
9:34612059:CT:C	donor_loss	0.8600
9:34612060:TCA:T	donor_loss	0.8600

AlphaMissense

1020 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:34611072:C:A	K75N	0.996
9:34611072:C:G	K75N	0.996
9:34611127:A:G	F57S	0.994
9:34611076:A:T	V74D	0.992
9:34611099:C:A	K66N	0.989
9:34611099:C:G	K66N	0.989
9:34611087:G:C	C70W	0.987
9:34610931:G:C	S122R	0.986
9:34610931:G:T	S122R	0.986
9:34610933:T:G	S122R	0.986
9:34611009:C:A	W96C	0.986
9:34611009:C:G	W96C	0.986
9:34611090:G:C	S69R	0.986
9:34611090:G:T	S69R	0.986
9:34611092:T:G	S69R	0.986
9:34611094:A:T	V68D	0.985
9:34611082:T:A	E72V	0.984
9:34611088:C:T	C70Y	0.983
9:34611089:A:G	C70R	0.983
9:34611121:C:T	G59D	0.983
9:34611193:T:A	K35I	0.982
9:34611214:A:G	M28T	0.982
9:34611208:A:T	V30D	0.981
9:34611190:A:G	I36T	0.979
9:34611074:T:C	K75E	0.978
9:34610932:C:A	S122I	0.976
9:34611011:A:G	W96R	0.974
9:34611011:A:T	W96R	0.974
9:34611169:G:T	A43D	0.974
9:34611192:T:A	K35N	0.974

dbSNP variants (sampled 300 via entrez): RS1000505174 (9:34611576 C>G), RS1000743330 (9:34610045 G>A), RS1002756597 (9:34612953 G>A), RS1003801732 (9:34613216 G>T), RS1004324586 (9:34613608 G>A), RS1004660741 (9:34612103 G>C), RS1004758818 (9:34610742 C>T), RS1005066166 (9:34612047 C>T), RS1006718957 (9:34613251 G>A), RS1006751539 (9:34613519 TCCTAGA>T), RS1008661750 (9:34612020 C>A), RS1009116692 (9:34612867 A>T), RS1009508776 (9:34611055 A>G), RS1009587114 (9:34612347 C>G,T), RS1011467606 (9:34613190 G>C,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_1352	Metabolite levels	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010365	lysophosphatidylcholine 22:6 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Smoke	decreases expression, increases abundance	2
Aflatoxin B1	decreases expression, decreases methylation	2
bisphenol F	affects cotreatment, increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
isobutyl alcohol	decreases expression, increases abundance, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
jinfukang	increases expression	1
Decitabine	affects expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	affects expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Estradiol	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Indomethacin	affects cotreatment, increases expression	1
Methapyrilene	decreases methylation	1
Polycyclic Aromatic Hydrocarbons	increases abundance, affects cotreatment, decreases expression	1
Ribonucleotides	affects binding	1
Thiram	decreases expression	1
Valproic Acid	affects expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	decreases expression	1
Sodium Selenite	increases expression	1

Clinical trials (associated diseases)

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