PRTFDC1

Summary

PRTFDC1 (phosphoribosyl transferase domain containing 1, HGNC:23333) is a protein-coding gene on chromosome 10p12.1, encoding Phosphoribosyltransferase domain-containing protein 1 (Q9NRG1). Has low, barely detectable phosphoribosyltransferase activity (in vitro).

Enables protein homodimerization activity. Predicted to be involved in purine ribonucleoside salvage. Predicted to be active in cytosol.

Source: NCBI Gene 56952 — RefSeq curated summary.

At a glance

• GWAS associations: 39
• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_020200

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23333
Approved symbol	PRTFDC1
Name	phosphoribosyl transferase domain containing 1
Location	10p12.1
Locus type	gene with protein product
Status	Approved
Aliases	HHGP
Ensembl gene	ENSG00000099256
Ensembl biotype	protein_coding
OMIM	610751
Entrez	56952

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000320152, ENST00000376376, ENST00000376378, ENST00000897639, ENST00000947509

RefSeq mRNA: 2 — MANE Select: NM_020200 NM_001282786, NM_020200

CCDS: CCDS60506, CCDS7145

Canonical transcript exons

ENST00000320152 — 9 exons

Exon	Start	End
ENSE00001124245	24952528	24952606
ENSE00001344057	24851388	24851464
ENSE00001344061	24855318	24855364
ENSE00001344065	24856913	24856995
ENSE00001344069	24871998	24872063
ENSE00001344073	24937184	24937367
ENSE00001344078	24942330	24942436
ENSE00001649958	24848614	24849891
ENSE00001702650	24858392	24858409

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 94.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.1667 / max 88.6392, expressed in 1292 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108706	5.9430	1279
205795	0.1279	45
108707	0.0958	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	94.09	gold quality
ventricular zone	UBERON:0003053	93.96	gold quality
ganglionic eminence	UBERON:0004023	93.47	gold quality
inferior vagus X ganglion	UBERON:0005363	92.93	gold quality
spinal cord	UBERON:0002240	92.48	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.30	gold quality
adrenal tissue	UBERON:0018303	91.38	gold quality
medulla oblongata	UBERON:0001896	91.02	gold quality
caudate nucleus	UBERON:0001873	90.81	gold quality
putamen	UBERON:0001874	90.80	gold quality
tibia	UBERON:0000979	90.70	gold quality
substantia nigra	UBERON:0002038	90.60	gold quality
subthalamic nucleus	UBERON:0001906	90.57	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.42	gold quality
midbrain	UBERON:0001891	90.27	gold quality
amygdala	UBERON:0001876	90.01	gold quality
nucleus accumbens	UBERON:0001882	89.75	gold quality
lateral globus pallidus	UBERON:0002476	89.72	gold quality
Ammon’s horn	UBERON:0001954	89.49	gold quality
pigmented layer of retina	UBERON:0001782	89.44	gold quality
jejunal mucosa	UBERON:0000399	89.33	gold quality
stromal cell of endometrium	CL:0002255	89.29	gold quality
cardiac muscle of right atrium	UBERON:0003379	89.07	gold quality
superior vestibular nucleus	UBERON:0007227	89.07	gold quality
right adrenal gland cortex	UBERON:0035827	88.96	gold quality
left adrenal gland cortex	UBERON:0035825	88.88	gold quality
adrenal cortex	UBERON:0001235	88.71	gold quality
left adrenal gland	UBERON:0001234	88.66	gold quality
temporal lobe	UBERON:0001871	88.56	gold quality
right adrenal gland	UBERON:0001233	88.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting PRTFDC1, 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-574-5P	100.00	66.01	989
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-4460	99.37	68.52	615
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-8065	99.19	70.38	1289
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-3125	99.14	68.49	2269

Literature-anchored findings (GeneRIF, showing 5)

• epigenetic silencing of PRTFDC1 by hypermethylation of the CpG island leads to a loss of PRTFDC1 function, which might be involved in squamous cell oral carcinogenesis. (PMID:17599052)
• The PRTFDC1 structure has been determined at 1.7 A resolution with bound GMP. The overall structure and GMP binding mode are very similar to that observed for HPRT. (PMID:21054786)
• These results demonstrate that PRTFDC1 is a genetic modifier of HPRT-deficiency in the mouse. (PMID:21818316)
• We found evidence for PRTFDC1 as a potential novel PTSD gene, a finding that awaits further replication. (PMID:25456346)
• rs12411980 single-nucleotide polymorphism related to PRTFDC1 expression is significantly associated with phantom tooth pain. (PMID:39093623)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	prtfdc1b	ENSDARG00000011683
danio_rerio	hprt1l	ENSDARG00000014866
danio_rerio	prtfdc1a	ENSDARG00000074528
rattus_norvegicus	Prtfdc1	ENSRNOG00000024874
drosophila_melanogaster	Pgm1	FBGN0003076
caenorhabditis_elegans		WBGENE00019890

Paralogs (6): PGM3 (ENSG00000013375), PGM1 (ENSG00000079739), PGM5 (ENSG00000154330), PGM2L1 (ENSG00000165434), HPRT1 (ENSG00000165704), PGM2 (ENSG00000169299)

Protein

Protein identifiers

Phosphoribosyltransferase domain-containing protein 1 — Q9NRG1 (reviewed: Q9NRG1)

All UniProt accessions (1): Q9NRG1

UniProt curated annotations — full annotation on UniProt →

Function. Has low, barely detectable phosphoribosyltransferase activity (in vitro). Binds GMP, IMP and alpha-D-5-phosphoribosyl 1-pyrophosphate (PRPP). Is not expected to contribute to purine metabolism or GMP salvage.

Subunit / interactions. Homodimer.

Similarity. Belongs to the purine/pyrimidine phosphoribosyltransferase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NRG1-1	1	yes
Q9NRG1-2	2
Q9NRG1-3	3

RefSeq proteins (2): NP_001269715, NP_064585* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000836	PRTase_dom	Domain
IPR005904	Hxn_phspho_trans	Family
IPR029057	PRTase-like	Homologous_superfamily
IPR050408	HGPRT	Family

Pfam: PF00156

UniProt features (32 total): strand 9, helix 8, binding site 7, splice variant 2, sequence conflict 2, initiator methionine 1, chain 1, turn 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2JBH	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRG1-F1	91.27	0.79

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 (7): 141–149; 141; 142; 173; 194–195; 201; 201

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 90 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOZGIT_ESR1_TARGETS_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_SALVAGE, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOBASE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_PURINE_NUCLEOBASE_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOSIDE_SALVAGE

GO Biological Process (1): purine ribonucleoside salvage (GO:0006166)

GO Molecular Function (6): nucleotide binding (GO:0000166), magnesium ion binding (GO:0000287), protein homodimerization activity (GO:0042803), hypoxanthine phosphoribosyltransferase activity (GO:0004422), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
purine-containing compound salvage	1
nucleoside salvage	1
purine ribonucleoside biosynthetic process	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
metal ion binding	1
identical protein binding	1
protein dimerization activity	1
purine phosphoribosyltransferase activity	1
binding	1
cation binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1615 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRTFDC1	APRT	P07741	608
PRTFDC1	ANKRD55	Q3KP44	570
PRTFDC1	TLL1	O43897	542
PRTFDC1	RNASE1	P07998	542
PRTFDC1	ZNF626	Q68DY1	487
PRTFDC1	GART	P22102	445
PRTFDC1	COBL	O75128	436
PRTFDC1	PPP1R14C	Q8TAE6	433
PRTFDC1	TIPE1	Q8WVP5	428
PRTFDC1	EN2	P19622	425
PRTFDC1	UMPS	P11172	423
PRTFDC1	GMPS	P49915	419
PRTFDC1	TK2	O00142	410
PRTFDC1	ZNF709	Q8N972	388
PRTFDC1	ADSS2	P30520	387

IntAct

93 interactions, top by confidence:

A	B	Type	Score
HPRT1	PRTFDC1	psi-mi:“MI:0915”(physical association)	0.920
PRTFDC1	HPRT1	psi-mi:“MI:0915”(physical association)	0.920
EEF2KMT	PRTFDC1	psi-mi:“MI:0915”(physical association)	0.830
PRTFDC1	EEF2KMT	psi-mi:“MI:0915”(physical association)	0.830
PRTFDC1	TCL1A	psi-mi:“MI:0915”(physical association)	0.720
PRTFDC1	EPM2AIP1	psi-mi:“MI:0915”(physical association)	0.720
TCL1A	PRTFDC1	psi-mi:“MI:0915”(physical association)	0.720
EPM2AIP1	PRTFDC1	psi-mi:“MI:0915”(physical association)	0.720
MCMBP	PRTFDC1	psi-mi:“MI:0915”(physical association)	0.720
PRTFDC1	GNPDA1	psi-mi:“MI:0915”(physical association)	0.560
PRTFDC1	LGALS9B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (65): PRTFDC1 (Two-hybrid), PRTFDC1 (Two-hybrid), PRTFDC1 (Two-hybrid), PRTFDC1 (Two-hybrid), MCMBP (Two-hybrid), EEF2KMT (Two-hybrid), LGALS9B (Two-hybrid), PRTFDC1 (Affinity Capture-MS), PRTFDC1 (Affinity Capture-MS), PRTFDC1 (Affinity Capture-MS), PRTFDC1 (Affinity Capture-MS), PRTFDC1 (Affinity Capture-MS), PRTFDC1 (Affinity Capture-MS), PRTFDC1 (Two-hybrid), NIF3L1 (Two-hybrid)

ESM2 similar proteins: A4II60, A5A6I1, B4S3A5, G5EDZ2, O42895, O65583, O74427, O94710, P00492, P00493, P00494, P07833, P09383, P20035, P27515, P27605, P41888, P43152, P47959, P56523, Q07010, Q10439, Q1RMS2, Q25566, Q26997, Q26998, Q27541, Q2M197, Q3SZ18, Q45FY6, Q55EL3, Q5F3Z1, Q64531, Q6DCP3, Q6GQ37, Q6LDD9, Q6LZE9, Q6WIT9, Q8VYB2, Q9FKS0

Diamond homologs: A4II60, A5A6I1, C0ZG45, O66821, O69537, P00492, P00493, P00494, P07833, P09383, P0A5T1, P0A9M2, P0A9M3, P0A9M4, P18134, P20035, P27605, P37171, P37472, P43152, P45078, P47959, P51900, P71479, P96794, P9WHQ8, P9WHQ9, Q02522, Q26997, Q3SZ18, Q45FY6, Q5HRP4, Q64531, Q6DCP3, Q6LDD9, Q6WIT9, Q724J4, Q839B2, Q8CQV4, Q8DRP8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2097 predictions. Top by Δscore:

Variant	Effect	Δscore
10:24855316:A:AC	donor_gain	1.0000
10:24855317:C:CC	donor_gain	1.0000
10:24855317:CAGT:C	donor_gain	1.0000
10:24856995:CCTT:C	acceptor_gain	1.0000
10:24872062:TT:T	acceptor_gain	1.0000
10:24872064:C:CC	acceptor_gain	1.0000
10:24937179:CTT:C	donor_loss	1.0000
10:24937180:TTA:T	donor_loss	1.0000
10:24937181:TAC:T	donor_loss	1.0000
10:24937182:A:AC	donor_gain	1.0000
10:24937182:A:T	donor_loss	1.0000
10:24937182:AC:A	donor_gain	1.0000
10:24937182:ACC:A	donor_gain	1.0000
10:24937183:C:CC	donor_gain	1.0000
10:24937183:CC:C	donor_gain	1.0000
10:24937183:CCC:C	donor_gain	1.0000
10:24937183:CCCT:C	donor_gain	1.0000
10:24937363:CAATT:C	acceptor_gain	1.0000
10:24937364:AATT:A	acceptor_gain	1.0000
10:24937365:ATT:A	acceptor_gain	1.0000
10:24937365:ATTC:A	acceptor_loss	1.0000
10:24937366:TT:T	acceptor_gain	1.0000
10:24937366:TTC:T	acceptor_loss	1.0000
10:24937367:TC:T	acceptor_loss	1.0000
10:24937368:C:A	acceptor_loss	1.0000
10:24937368:C:CC	acceptor_gain	1.0000
10:24937369:T:C	acceptor_loss	1.0000
10:24851386:A:AC	donor_gain	0.9900
10:24851387:C:CC	donor_gain	0.9900
10:24851466:T:C	acceptor_gain	0.9900

AlphaMissense

1494 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:24937205:G:C	F106L	0.996
10:24937205:G:T	F106L	0.996
10:24937207:A:G	F106L	0.996
10:24851428:C:T	G197E	0.995
10:24851454:A:C	F188L	0.994
10:24851454:A:T	F188L	0.994
10:24851456:A:G	F188L	0.994
10:24851429:C:G	G197R	0.993
10:24851429:C:T	G197R	0.993
10:24851436:A:C	F194L	0.992
10:24851436:A:T	F194L	0.992
10:24851438:A:G	F194L	0.992
10:24937269:A:G	L85P	0.992
10:24851455:A:G	F188S	0.991
10:24858396:A:T	V140D	0.991
10:24849887:A:T	I212K	0.990
10:24851397:T:A	R207S	0.990
10:24851397:T:G	R207S	0.990
10:24851398:C:A	R207I	0.990
10:24851398:C:G	R207T	0.990
10:24851428:C:A	G197V	0.990
10:24855364:A:C	S169R	0.990
10:24855364:A:T	S169R	0.990
10:24856914:T:G	S169R	0.990
10:24858405:A:T	V137D	0.990
10:24937280:G:C	F81L	0.990
10:24937280:G:T	F81L	0.990
10:24937282:A:G	F81L	0.990
10:24937367:T:A	R52S	0.990
10:24937367:T:G	R52S	0.990

dbSNP variants (sampled 300 via entrez): RS1000007917 (10:24860416 C>T), RS1000087551 (10:24905072 C>T), RS1000092291 (10:24947201 C>A), RS1000114115 (10:24860971 T>C), RS1000117714 (10:24930744 C>T), RS1000159606 (10:24924896 G>A), RS1000177208 (10:24864293 G>T), RS1000236050 (10:24919180 A>C), RS1000280763 (10:24878054 G>A,T), RS1000368065 (10:24872725 A>T), RS1000372842 (10:24889993 G>C), RS1000419708 (10:24912605 T>C), RS1000426543 (10:24947640 T>C), RS1000433011 (10:24954587 C>A,G), RS1000434166 (10:24851865 C>G,T)

Disease associations

OMIM: gene MIM:610751 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

39 associations (top):

Study	Trait	p-value
GCST001762_334	Obesity-related traits	3.000000e-06
GCST002118_1	Metabolite levels (Pyroglutamine)	4.000000e-06
GCST002681_1	Post-traumatic stress disorder	2.000000e-09
GCST002875_1	Diisocyanate-induced asthma	5.000000e-06
GCST004603_50	Platelet count	4.000000e-10
GCST004607_114	Plateletcrit	7.000000e-13
GCST004610_108	White blood cell count	1.000000e-44
GCST004611_50	High light scatter reticulocyte count	1.000000e-205
GCST004612_106	High light scatter reticulocyte percentage of red cells	6.000000e-202
GCST004613_14	Sum neutrophil eosinophil counts	3.000000e-32
GCST004614_35	Granulocyte count	2.000000e-32
GCST004619_203	Reticulocyte fraction of red cells	8.000000e-163
GCST004620_113	Sum basophil neutrophil counts	3.000000e-32
GCST004621_12	Red cell distribution width	6.000000e-16
GCST004622_29	Reticulocyte count	2.000000e-163
GCST004625_176	Monocyte count	8.000000e-48
GCST004626_76	Myeloid white cell count	3.000000e-39
GCST004627_7	Lymphocyte count	9.000000e-17
GCST004628_108	Immature fraction of reticulocytes	4.000000e-139
GCST004629_87	Neutrophil count	2.000000e-32
GCST005580_102	Intraocular pressure	4.000000e-08
GCST005580_185	Intraocular pressure	2.000000e-08
GCST008764_3	Perceived intensity of neohesperidin dihydrochalcone	8.000000e-06
GCST90000025_394	Appendicular lean mass	3.000000e-40
GCST90002381_320	Eosinophil count	1.000000e-14
GCST90002385_473	High light scatter reticulocyte count	0.000000e+00
GCST90002386_394	High light scatter reticulocyte percentage of red cells	0.000000e+00
GCST90002387_350	Immature fraction of reticulocytes	1.000000e-308
GCST90002388_550	Lymphocyte count	1.000000e-47
GCST90002393_326	Monocyte count	1.000000e-95

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0005106	body composition measurement
EFO:0005408	pyroglutamine measurement
EFO:0006995	response to diisocyanate
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0007986	reticulocyte count
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0009188	Red cell distribution width
EFO:0005091	monocyte count
EFO:0004587	lymphocyte count
EFO:0004695	intraocular pressure measurement
EFO:0004980	appendicular lean mass
EFO:0007984	platelet component distribution width
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	4
bisphenol A	affects cotreatment, increases methylation, decreases expression	3
arsenite	affects binding, increases reaction, increases methylation	2
sodium arsenite	affects acetylation, affects methylation, increases expression	2
(+)-JQ1 compound	decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression, increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	decreases expression	1
methylparaben	decreases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	affects methylation, affects acetylation	1
abrine	decreases expression	1
bisphenol S	increases methylation	1
jinfukang	decreases expression	1
Temozolomide	decreases expression	1
Decitabine	affects methylation	1
Sunitinib	decreases expression	1
Zoledronic Acid	decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Arsenic	affects methylation	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Flame Retardants	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1

Clinical trials (associated diseases)

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