PRCC

Summary

PRCC (proline rich mitotic checkpoint control factor, HGNC:9343) is a protein-coding gene on chromosome 1q23.1, encoding Proline-rich protein PRCC (Q92733). May regulate cell cycle progression through interaction with MAD2L2. It is a selective cancer dependency (DepMap: 20.9% of cell lines).

This gene encodes a protein that may play a role in pre-mRNA splicing. Chromosomal translocations (X;1)(p11;q21) that result in fusion of this gene to TFE3 (GeneID 7030) have been associated with papillary renal cell carcinoma. A PRCC-TFE3 fusion protein is expressed in affected carcinomas and is likely associated with altered gene transactivation. This fusion protein has also been associated with disruption of the cell cycle.

Source: NCBI Gene 5546 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 82 total
• Phenotypes (HPO): 4
• Cancer dependency (DepMap): dependent in 20.9% of screened cell lines
• MANE Select transcript: NM_005973

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9343
Approved symbol	PRCC
Name	proline rich mitotic checkpoint control factor
Location	1q23.1
Locus type	gene with protein product
Status	Approved
Aliases	RCCP1
Ensembl gene	ENSG00000143294
Ensembl biotype	protein_coding
OMIM	179755
Entrez	5546

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 21 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000271526, ENST00000454659, ENST00000459707, ENST00000469071, ENST00000473387, ENST00000491853, ENST00000526188, ENST00000888086, ENST00000888087, ENST00000888088, ENST00000888089, ENST00000888090, ENST00000888091, ENST00000888092, ENST00000927762, ENST00000927763, ENST00000927764, ENST00000927765, ENST00000927766, ENST00000927767, ENST00000927768, ENST00000927769, ENST00000950490, ENST00000950491, ENST00000950492

RefSeq mRNA: 1 — MANE Select: NM_005973 NM_005973

CCDS: CCDS1157

Canonical transcript exons

ENST00000271526 — 7 exons

Exon	Start	End
ENSE00000959080	156794665	156794808
ENSE00000959081	156797276	156797341
ENSE00001833466	156767535	156768239
ENSE00001870245	156800374	156800815
ENSE00003510161	156786608	156787174
ENSE00003525835	156782282	156782329
ENSE00003607660	156791697	156791792

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 96.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.7872 / max 357.8567, expressed in 1821 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5775	56.8173	1820
5776	0.3372	152
5777	0.2468	83
5771	0.1953	99
5774	0.1310	31
5773	0.0597	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.92	gold quality
ganglionic eminence	UBERON:0004023	96.53	gold quality
ventricular zone	UBERON:0003053	95.57	gold quality
cerebellar hemisphere	UBERON:0002245	95.26	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.26	gold quality
cerebellar cortex	UBERON:0002129	95.17	gold quality
right frontal lobe	UBERON:0002810	94.99	gold quality
skin of leg	UBERON:0001511	94.95	gold quality
right lobe of thyroid gland	UBERON:0001119	94.83	gold quality
skin of abdomen	UBERON:0001416	94.82	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.82	gold quality
gastrocnemius	UBERON:0001388	94.78	gold quality
stromal cell of endometrium	CL:0002255	94.61	gold quality
mucosa of transverse colon	UBERON:0004991	94.56	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.35	gold quality
left lobe of thyroid gland	UBERON:0001120	94.32	gold quality
body of uterus	UBERON:0009853	94.23	gold quality
apex of heart	UBERON:0002098	94.20	gold quality
lower esophagus mucosa	UBERON:0035834	94.16	gold quality
muscle of leg	UBERON:0001383	94.14	gold quality
granulocyte	CL:0000094	94.11	gold quality
right lung	UBERON:0002167	94.10	gold quality
endocervix	UBERON:0000458	94.02	gold quality
ectocervix	UBERON:0012249	93.96	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.93	gold quality
left uterine tube	UBERON:0001303	93.92	gold quality
lower esophagus	UBERON:0013473	93.92	gold quality
right ovary	UBERON:0002118	93.85	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.83	gold quality
prefrontal cortex	UBERON:0000451	93.77	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.79
E-GEOD-110499	no	253.81
E-MTAB-8060	no	111.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting PRCC, 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-548C-3P	99.99	74.01	7587
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-4494	97.86	64.93	850
HSA-MIR-2278	97.30	66.19	1130
HSA-MIR-1225-3P	97.29	64.60	876

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 20.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• Our data suggest a scenario in which, during the course of renal cell carcinoma development, an initial PRCCTFE3-induced cell cycle delay must be numbed, thus permitting continued proliferation and progression towards full-blown malignancy. (PMID:19422821)
• results reveal that PRCC-TFE3 dual-fusion FISH probe is an efficient and concise technique for diagnosing PRCC-TFE3 RCC in paraffin-embedded tissue (PMID:28949976)
• PRCC-TFE3 fusion-mediated PRKN/parkin-dependent mitophagy promotes cell survival and proliferation in PRCC-TFE3 translocation renal cell carcinoma. (PMID:33019842)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prcc	ENSDARG00000063252
mus_musculus	Prcc	ENSMUSG00000004895
rattus_norvegicus	Prcc	ENSRNOG00000012933
drosophila_melanogaster	CG17249	FBGN0035249
caenorhabditis_elegans		WBGENE00008034

Protein

Protein identifiers

Proline-rich protein PRCC — Q92733 (reviewed: Q92733)

Alternative names: Papillary renal cell carcinoma translocation-associated gene protein

All UniProt accessions (4): Q92733, A0A0S2Z456, H0Y679, H0YE12

UniProt curated annotations — full annotation on UniProt →

Function. May regulate cell cycle progression through interaction with MAD2L2.

Subunit / interactions. Interacts with MAD2L2; the interaction is direct.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous in fetal and adult tissues.

Disease relevance. A chromosomal aberration involving PRCC is found in patients with papillary renal cell carcinoma. Translocation t(X;1)(p11.2;q21.2) with TFE3.

RefSeq proteins (1): NP_005964* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018800	PRCC	Family

Pfam: PF10253

UniProt features (22 total): modified residue 9, compositionally biased region 7, region of interest 4, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92733-F1	59.89	0.06

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 (9): 97, 114, 157, 159, 212, 218, 239, 241, 267

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 156 (showing top): PATIL_LIVER_CANCER, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_REGULATION_OF_CELL_CYCLE, REACTOME_MRNA_SPLICING, MYLLYKANGAS_AMPLIFICATION_HOT_SPOT_17, TANAKA_METHYLATED_IN_ESOPHAGEAL_CARCINOMA, BOYAULT_LIVER_CANCER_SUBCLASS_G12_UP, MODULE_18, MYLLYKANGAS_AMPLIFICATION_HOT_SPOT_24, DURCHDEWALD_SKIN_CARCINOGENESIS_DN, REACTOME_METABOLISM_OF_RNA, TGGAAA_NFAT_Q4_01, GOCC_NUCLEAR_SPECK, GOCC_NUCLEAR_BODY, TCCCRNNRTGC_UNKNOWN

GO Biological Process (1): regulation of cell cycle (GO:0051726)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear speck (GO:0016607)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
mRNA Splicing	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell cycle	1
regulation of cellular process	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

1256 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRCC	ASPSCR1	Q9BZE9	967
PRCC	TFE3	P19532	964
PRCC	TFEB	P19484	820
PRCC	CLTC	Q00610	820
PRCC	SFPQ	P23246	812
PRCC	MAD2L2	Q9UI95	760
PRCC	NONO	P30807	716
PRCC	LUC7L3	O95232	710
PRCC	ZNF830	Q96NB3	696
PRCC	CRNKL1	Q9BZJ0	682
PRCC	TBC1D25	Q3MII6	669
PRCC	RBM10	P98175	658
PRCC	HLF	Q16534	649
PRCC	MITF	O75030	644
PRCC	KANSL2	Q9H9L4	638

IntAct

84 interactions, top by confidence:

A	B	Type	Score
PRCC	NTC20	psi-mi:“MI:0915”(physical association)	0.560
PRCC	HOMER3	psi-mi:“MI:0915”(physical association)	0.560
EGFR	PRCC	psi-mi:“MI:0915”(physical association)	0.550
IWS1	SUPT5H	psi-mi:“MI:0914”(association)	0.530
PRCC	BCAS2	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	SEC16A	psi-mi:“MI:0914”(association)	0.530
FKBP9	CASC3	psi-mi:“MI:0914”(association)	0.530
PLOD3	PLOD2	psi-mi:“MI:0914”(association)	0.530
CSNK2A1	PRCC	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PRCC	DNAJC10	psi-mi:“MI:0915”(physical association)	0.400
SF3A2	PRCC	psi-mi:“MI:0915”(physical association)	0.400
RBM10	PRCC	psi-mi:“MI:0915”(physical association)	0.370
LSM2	PRCC	psi-mi:“MI:0915”(physical association)	0.370
PRCC	PRPF19	psi-mi:“MI:0915”(physical association)	0.370
PPIL2	PRCC	psi-mi:“MI:0915”(physical association)	0.370
PRCC	TOE1	psi-mi:“MI:0915”(physical association)	0.370
CEP170P1	PCYT1A	psi-mi:“MI:0914”(association)	0.350
Bcas2	PEX10	psi-mi:“MI:0914”(association)	0.350
YWHAZ	WDR62	psi-mi:“MI:0914”(association)	0.350
Crnkl1	PLRG1	psi-mi:“MI:0914”(association)	0.350
HSF2	RBBP6	psi-mi:“MI:0914”(association)	0.350
SOD1	FAAP20	psi-mi:“MI:0914”(association)	0.350
LRP8	TYK2	psi-mi:“MI:0914”(association)	0.350

BioGRID (122): PRCC (Affinity Capture-MS), PRCC (Proximity Label-MS), PRCC (Affinity Capture-MS), PRCC (Affinity Capture-MS), PRCC (Affinity Capture-MS), PRCC (Affinity Capture-MS), PRCC (Affinity Capture-MS), PRCC (Affinity Capture-MS), PRCC (Affinity Capture-MS), PRCC (Affinity Capture-MS), PRCC (Affinity Capture-MS), PRCC (Affinity Capture-MS), PRCC (Affinity Capture-MS), PRCC (Affinity Capture-MS), PRCC (Affinity Capture-MS)

ESM2 similar proteins: A4PB26, D3ZTQ1, G1SW77, O16053, O88271, Q12872, Q32LE2, Q3MHS2, Q3U155, Q3USH5, Q4ADK4, Q4ADK7, Q4VAA2, Q5M8L3, Q5PQP2, Q5PQS7, Q5RKH3, Q5VSY0, Q5XHI2, Q5XIG5, Q5XIM5, Q5ZLH9, Q60FC2, Q63ZM9, Q6AXS5, Q6DIS2, Q6DJ13, Q6GNQ4, Q6NWC9, Q6PFK1, Q75UQ2, Q7T370, Q7ZYA6, Q8HXY9, Q8K039, Q8MMC4, Q8NC51, Q8R1N0, Q92733, Q96NB3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRCC	up-regulates	MAD2L2	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 104 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
mRNA 3’-end processing	7	18.9×	4e-06
Transport of Mature mRNA derived from an Intron-Containing Transcript	8	16.7×	1e-06
mRNA Splicing	11	16.6×	4e-09
Processing of Capped Intron-Containing Pre-mRNA	14	15.8×	3e-11
mRNA Splicing - Minor Pathway	5	15.3×	8e-04
RNA Polymerase II Transcription Termination	5	15.0×	8e-04
mRNA Splicing - Major Pathway	20	15.0×	6e-16
mRNA Polyadenylation	12	14.4×	3e-09

GO biological processes:

GO term	Partners	Fold	FDR
mRNA transport	7	19.4×	2e-05
mRNA splicing, via spliceosome	17	16.4×	2e-13
negative regulation of translation	6	12.4×	1e-03
mRNA processing	12	9.9×	1e-06
RNA splicing	9	8.4×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1399 predictions. Top by Δscore:

Variant	Effect	Δscore
1:156782276:TCTTA:T	acceptor_loss	1.0000
1:156782277:CTTA:C	acceptor_loss	1.0000
1:156782278:TTAG:T	acceptor_loss	1.0000
1:156782279:TA:T	acceptor_loss	1.0000
1:156782280:A:AG	acceptor_gain	1.0000
1:156782280:AGT:A	acceptor_loss	1.0000
1:156782281:G:C	acceptor_loss	1.0000
1:156782281:G:GA	acceptor_gain	1.0000
1:156782281:GTC:G	acceptor_gain	1.0000
1:156782281:GTCA:G	acceptor_gain	1.0000
1:156782330:GTAAG:G	donor_loss	1.0000
1:156782331:T:A	donor_loss	1.0000
1:156786587:T:G	acceptor_gain	1.0000
1:156786593:A:AG	acceptor_gain	1.0000
1:156786593:ACCT:A	acceptor_gain	1.0000
1:156786593:ACCTG:A	acceptor_gain	1.0000
1:156786596:T:TA	acceptor_gain	1.0000
1:156791790:GCA:G	donor_gain	1.0000
1:156791793:G:GG	donor_gain	1.0000
1:156791798:T:G	donor_gain	1.0000
1:156794659:TTCCA:T	acceptor_gain	1.0000
1:156794660:TCCAG:T	acceptor_gain	1.0000
1:156794661:CCA:C	acceptor_gain	1.0000
1:156794662:CAG:C	acceptor_gain	1.0000
1:156794663:A:AG	acceptor_gain	1.0000
1:156794663:AG:A	acceptor_gain	1.0000
1:156794664:G:A	acceptor_gain	1.0000
1:156794664:G:GT	acceptor_gain	1.0000
1:156794664:GT:G	acceptor_gain	1.0000
1:156794664:GTT:G	acceptor_gain	1.0000

AlphaMissense

3159 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:156786825:T:A	I245N	1.000
1:156786837:C:A	A249D	1.000
1:156797292:C:A	P447Q	1.000
1:156797307:G:C	R452P	1.000
1:156797310:G:C	R453P	1.000
1:156797312:A:G	K454E	1.000
1:156797313:A:T	K454I	1.000
1:156797314:A:C	K454N	1.000
1:156797314:A:T	K454N	1.000
1:156797315:C:G	H455D	1.000
1:156797316:A:C	H455P	1.000
1:156797317:C:A	H455Q	1.000
1:156797317:C:G	H455Q	1.000
1:156797319:A:C	Q456P	1.000
1:156797322:T:A	I457N	1.000
1:156797322:T:C	I457T	1.000
1:156797322:T:G	I457S	1.000
1:156797327:T:A	Y459N	1.000
1:156797327:T:C	Y459H	1.000
1:156797327:T:G	Y459D	1.000
1:156797331:T:A	L460H	1.000
1:156797331:T:C	L460P	1.000
1:156797331:T:G	L460R	1.000
1:156797334:T:A	I461N	1.000
1:156797336:C:G	H462D	1.000
1:156797337:A:C	H462P	1.000
1:156797340:A:C	Q463P	1.000
1:156800374:G:C	A464P	1.000
1:156800375:C:A	A464D	1.000
1:156800384:G:C	R467P	1.000

dbSNP variants (sampled 300 via entrez): RS1000093462 (1:156799626 T>C), RS1000155101 (1:156785598 A>G,T), RS1000176720 (1:156786447 C>T), RS1000357472 (1:156793235 G>C), RS1000371192 (1:156792899 C>T), RS1000460168 (1:156786137 A>G), RS1000473839 (1:156773842 A>G), RS1000536870 (1:156766750 C>T), RS1000626471 (1:156780161 G>A,C), RS1000762210 (1:156787452 T>C,G), RS1000847451 (1:156774126 G>A,C), RS1000968408 (1:156791302 C>T), RS1000997257 (1:156767133 G>A), RS1001089561 (1:156787743 C>T), RS1001098141 (1:156798238 T>C)

Disease associations

OMIM: gene MIM:179755 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (1): Hereditary papillary renal cell carcinoma (Orphanet:47044)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0003829	Typified by incomplete penetrance
HP:0006766	Papillary renal cell carcinoma

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004061_1	Sjögren’s syndrome	2.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression, affects cotreatment	2
Cadmium Chloride	increases abundance, decreases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenite	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Cadmium	decreases expression, increases abundance	1
Caffeine	increases phosphorylation	1
Dactinomycin	affects cotreatment, increases secretion	1
Doxorubicin	decreases expression	1
Ketoconazole	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	increases phosphorylation	1
Urethane	increases expression	1
Valproic Acid	increases expression	1
Aflatoxin B1	increases methylation	1

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B099	UOK120	Cancer cell line	Male
CVCL_B105	UOK124	Cancer cell line	Female
CVCL_B123	UOK146	Cancer cell line	Female
CVCL_B3EQ	Abcam HEK293T PRCC KO	Transformed cell line	Female
CVCL_WY83	CL89-12117	Cancer cell line	Male
CVCL_WY84	CL89-17872	Cancer cell line	Male

Clinical trials (associated diseases)

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