CSTF2T

Summary

CSTF2T (cleavage stimulation factor subunit 2 tau variant, HGNC:17086) is a protein-coding gene on chromosome 10q21.1, encoding Cleavage stimulation factor subunit 2 tau variant (Q9H0L4). May play a significant role in AAUAAA-independent mRNA polyadenylation in germ cells.

Enables RNA binding activity. Predicted to be involved in mRNA 3’-end processing. Located in nucleoplasm.

Source: NCBI Gene 23283 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 93 total
• MANE Select transcript: NM_015235

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17086
Approved symbol	CSTF2T
Name	cleavage stimulation factor subunit 2 tau variant
Location	10q21.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434C1013, KIAA0689, CstF-64T, tauCstF-64
Ensembl gene	ENSG00000177613
Ensembl biotype	protein_coding
OMIM	611968
Entrez	23283

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000331173

RefSeq mRNA: 1 — MANE Select: NM_015235 NM_015235

CCDS: CCDS7245

Canonical transcript exons

ENST00000331173 — 1 exons

Exon	Start	End
ENSE00001324439	51695486	51699595

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 91.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.5406 / max 692.9407, expressed in 1815 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109372	27.3733	1815
109371	0.1673	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	91.44	gold quality
germinal epithelium of ovary	UBERON:0001304	90.87	gold quality
choroid plexus epithelium	UBERON:0003911	90.77	gold quality
parietal pleura	UBERON:0002400	87.53	gold quality
pons	UBERON:0000988	87.36	gold quality
islet of Langerhans	UBERON:0000006	87.09	gold quality
ganglionic eminence	UBERON:0004023	87.07	gold quality
corpus callosum	UBERON:0002336	86.76	gold quality
descending thoracic aorta	UBERON:0002345	86.68	gold quality
subthalamic nucleus	UBERON:0001906	86.57	gold quality
cortical plate	UBERON:0005343	86.57	gold quality
cervix squamous epithelium	UBERON:0006922	86.57	gold quality
skeletal muscle tissue	UBERON:0001134	86.56	gold quality
biceps brachii	UBERON:0001507	86.46	gold quality
hair follicle	UBERON:0002073	86.24	silver quality
Brodmann (1909) area 23	UBERON:0013554	86.15	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.13	gold quality
lymph node	UBERON:0000029	86.07	gold quality
inferior vagus X ganglion	UBERON:0005363	85.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.79	gold quality
ventricular zone	UBERON:0003053	85.78	gold quality
ventral tegmental area	UBERON:0002691	85.75	gold quality
muscle of leg	UBERON:0001383	85.72	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	85.69	gold quality
pleura	UBERON:0000977	85.64	gold quality
muscle tissue	UBERON:0002385	85.64	gold quality
superficial temporal artery	UBERON:0001614	85.57	gold quality
spinal cord	UBERON:0002240	85.56	gold quality
muscle organ	UBERON:0001630	85.55	gold quality
heart right ventricle	UBERON:0002080	85.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

128 targeting CSTF2T, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426

Literature-anchored findings (GeneRIF, showing 7)

• Radiation hybrid mapping places the human tauCstF-64 gene at 10q22-q23, which is the site of a translocation that has been associated with human neurological problems and male infertility. (PMID:12408968)
• structure of the RNA-binding domain of CstF-64 containing an RNA recognition motif (RRM) augmented by N- and C-terminal helices (PMID:12773396)
• upstream element in human papillomavirus type 16 interacted specifically with CstF-64, hnRNP C1/C2 & polypyrimidine tract binding protein, suggesting these factors were enhancing or regulating polyadenylation at the HPV-16 early polyadenylation signal (PMID:15767428)
• Studied expression levels of CstF-64 in EV71-infected cells; showed reduction of CstF-64 during virus infection correlated with production of viral 3C(pro). CstF-64 was cleaved in vitro by 3C(pro) not by mutant 3C(pro) variants. (PMID:19779565)
• CstF64 and CstF64tau modulate one another’s expression and play overlapping as well as distinct roles in regulating global alternative polyadenylation profiles. (PMID:24149845)
• CSTF2tau binds many previously not recognized RNAs including histone, snoRNA and snRNAs. CSTF2tau-binding is associated with internal oligoadenylation resulting in shortened snRNA isoforms subjected to rapid degradation. CSTF2tau controls the abundance of snRNAs resulting in alternative splicing of several RNAs with critical roles in tumorigenesis and cardiac function. (PMID:28334977)
• CSTF2T up-regulates IGHG1 by binding to ZEB1 to promote melanoma cell proliferation, migration, and invasion. (PMID:36736099)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cstf2t	ENSMUSG00000053536
rattus_norvegicus	Cstf2t	ENSRNOG00000070422
drosophila_melanogaster	CstF64	FBGN0027841
caenorhabditis_elegans		WBGENE00000774
caenorhabditis_elegans	R06C1.4	WBGENE00011059

Paralogs (5): U2AF2 (ENSG00000063244), CSTF2 (ENSG00000101811), RBMX2 (ENSG00000134597), ZCRB1 (ENSG00000139168), UHMK1 (ENSG00000152332)

Protein

Protein identifiers

Cleavage stimulation factor subunit 2 tau variant — Q9H0L4 (reviewed: Q9H0L4)

Alternative names: CF-1 64 kDa subunit tau variant, Cleavage stimulation factor 64 kDa subunit tau variant, TauCstF-64

All UniProt accessions (1): Q9H0L4

UniProt curated annotations — full annotation on UniProt →

Function. May play a significant role in AAUAAA-independent mRNA polyadenylation in germ cells. Directly involved in the binding to pre-mRNAs.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_056050* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR025742	CSTF2_hinge	Domain
IPR026896	CSTF_C	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR038192	CSTF_C_sf	Homologous_superfamily

Pfam: PF00076, PF14304, PF14327

UniProt features (33 total): repeat 18, region of interest 5, compositionally biased region 4, modified residue 2, sequence conflict 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0L4-F1	60.27	0.14

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 (2): 320, 563

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-72187	mRNA 3’-end processing
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-77595	Processing of Intronless Pre-mRNAs
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA

MSigDB gene sets: 139 (showing top): BROWNE_HCMV_INFECTION_6HR_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MATTIOLI_MGUS_VS_PCL, chr10q21, BOYLAN_MULTIPLE_MYELOMA_D_DN, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_DN, GOBP_REGULATION_OF_MRNA_3_END_PROCESSING, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_MRNA_3_END_PROCESSING, GARY_CD5_TARGETS_DN, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, REACTOME_METABOLISM_OF_RNA, OSMAN_BLADDER_CANCER_DN

GO Biological Process (2): mRNA 3’-end processing (GO:0031124), mRNA processing (GO:0006397)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA binding (GO:0003729), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (3): nucleoplasm (GO:0005654), mRNA cleavage and polyadenylation specificity factor complex (GO:0005847), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Processing of Capped Intron-Containing Pre-mRNA	1
RNA Polymerase II Transcription	1
Processing of Capped Intronless Pre-mRNA	1
mRNA 3’-end processing	1
Dengue Virus Infection	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
mRNA processing	1
RNA 3’-end processing	1
RNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
RNA binding	1
nuclear lumen	1
cellular anatomical structure	1
mRNA cleavage factor complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2608 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSTF2T	LMOD1	P29536	760
CSTF2T	CSTF3	Q12996	742
CSTF2T	CSTF1	Q05048	715
CSTF2T	CPSF1	Q10570	665
CSTF2T	NUDT21	O43809	664
CSTF2T	CPSF3	Q9UKF6	646
CSTF2T	PCF11	O94913	615
CSTF2T	CPSF2	Q9P2I0	613
CSTF2T	SYMPK	Q92797	605
CSTF2T	WDR33	Q9C0J8	601
CSTF2T	CPSF4	O95639	563
CSTF2T	CPSF6	Q16630	549
CSTF2T	NONO	P30807	532
CSTF2T	FIP1L1	Q6UN15	525
CSTF2T	PAPOLG	Q9BWT3	487

IntAct

128 interactions, top by confidence:

A	B	Type	Score
FANCG	FANCA	psi-mi:“MI:0914”(association)	0.960
RFX5	RFXAP	psi-mi:“MI:0914”(association)	0.880
UBQLN1	CSTF2T	psi-mi:“MI:0915”(physical association)	0.780
CSTF2T	UBQLN1	psi-mi:“MI:0915”(physical association)	0.780
BIRC2	HTRA2	psi-mi:“MI:0914”(association)	0.650
CSTF2T	HGS	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	CSTF2T	psi-mi:“MI:0915”(physical association)	0.560
HGS	CSTF2T	psi-mi:“MI:0915”(physical association)	0.560
CSTF2T		psi-mi:“MI:0915”(physical association)	0.560
FOXJ2	CSTF2T	psi-mi:“MI:0915”(physical association)	0.560
CSTF2T	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
CTAG1A	CSTF2T	psi-mi:“MI:0915”(physical association)	0.560
PKNOX2	CSTF2T	psi-mi:“MI:0915”(physical association)	0.560
CSTF2T	COL17A1	psi-mi:“MI:0915”(physical association)	0.560
TLE5	CSTF2T	psi-mi:“MI:0915”(physical association)	0.560
FAM168B	CSTF2T	psi-mi:“MI:0915”(physical association)	0.560
LASP1	CSTF2T	psi-mi:“MI:0915”(physical association)	0.560
CSTF2T	AKAP8L	psi-mi:“MI:0915”(physical association)	0.560
CSTF2T	SMYD3	psi-mi:“MI:0915”(physical association)	0.560
CTDSP1	CSTF2T	psi-mi:“MI:0915”(physical association)	0.560
FOXI1	CSTF2T	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (132): CSTF2T (Two-hybrid), UBQLN1 (Two-hybrid), CSTF2T (Affinity Capture-MS), UBQLN1 (Two-hybrid), CSTF1 (Co-fractionation), CSTF2T (Co-fractionation), CSTF2T (Co-fractionation), CSTF2T (Co-fractionation), CSTF2T (Co-fractionation), CSTF2T (Affinity Capture-Western), CSTF2T (Proximity Label-MS), GOLGA2 (Two-hybrid), CSTF2T (Affinity Capture-MS), CSTF2T (Affinity Capture-MS), CSTF2T (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q7JC00, A0JM64, A0JNC2, A2VE44, A4IHD9, B2C6R6, B5DE09, B8BCZ8, E7F1H9, F4JT98, O09000, O57539, P78364, Q0WVM7, Q15596, Q17BA4, Q2NLB0, Q3TCX3, Q5RDA3, Q5TP13, Q5ZL54, Q61026, Q64028, Q6GP15, Q6K271, Q6NS15, Q6PEH8, Q71SY5, Q7XYY2, Q7ZVN7, Q80TM6, Q8C7E9, Q8CHY6, Q8HXM1, Q8IZL2, Q8VCB2, Q8W234, Q90WJ3, Q924H2, Q940A7

Diamond homologs: A0A0F6MY85, O02008, P19018, P33240, Q05AT9, Q16560, Q1LZH0, Q4KMD3, Q5RDA3, Q5U1W5, Q8BIQ5, Q8C7E9, Q8HXM1, Q8LPQ9, Q9D384, Q9H0L4, Q9SHZ6, A0A8M1NHK4, A0AV96, A0JM51, A4FV72, A4QUF0, A8WLV5, O01671, O04425, O43040, O43390, O60506, P28659, P86049, Q08BH5, Q08E07, Q0P4R6, Q0V9L3, Q10B98, Q14498, Q28HE9, Q2HJG2, Q2UK72, Q3UEB3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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
Processing of Intronless Pre-mRNAs	6	57.1×	2e-07
mRNA 3’-end processing	7	23.0×	2e-06
RNA Polymerase II Transcription Termination	6	22.0×	2e-05
mRNA Polyadenylation	10	14.6×	2e-07
Dengue Virus-Host Interactions	11	8.4×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
mRNA processing	9	8.8×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	89
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

93 predictions. Top by Δscore:

Variant	Effect	Δscore
10:51698941:G:A	donor_gain	0.9400
10:51699080:T:TA	donor_gain	0.9300
10:51695633:GAATT:G	donor_gain	0.8900
10:51695634:AATTA:A	donor_gain	0.8900
10:51699437:T:TA	donor_gain	0.7700
10:51699456:A:C	donor_gain	0.7300
10:51698970:T:TA	donor_gain	0.6800
10:51696106:CA:C	acceptor_gain	0.6300
10:51699466:AGTTG:A	donor_gain	0.6200
10:51699449:T:TA	donor_gain	0.6100
10:51698938:T:C	donor_gain	0.5700
10:51699018:C:CT	donor_gain	0.5300
10:51699019:T:TT	donor_gain	0.5300
10:51696977:TAGAA:T	acceptor_gain	0.4700
10:51698931:A:AC	donor_gain	0.4700
10:51698932:C:CC	donor_gain	0.4700
10:51698967:T:C	donor_gain	0.4600
10:51699529:T:TA	donor_gain	0.4400
10:51699433:A:T	donor_gain	0.4300
10:51696606:CT:C	acceptor_gain	0.3900
10:51696625:T:A	acceptor_gain	0.3900
10:51699254:T:TA	donor_gain	0.3800
10:51699470:G:A	donor_gain	0.3800
10:51696107:A:C	acceptor_gain	0.3600
10:51699309:C:CA	donor_gain	0.3600
10:51699431:CCAA:C	donor_loss	0.3600
10:51699432:CAACC:C	donor_loss	0.3600
10:51699433:AAC:A	donor_loss	0.3600
10:51699434:A:AC	donor_loss	0.3600
10:51699435:C:A	donor_loss	0.3600

AlphaMissense

3970 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:51697724:A:C	I609S	1.000
10:51697724:A:G	I609T	1.000
10:51697724:A:T	I609N	1.000
10:51697727:T:G	Q608P	1.000
10:51697732:C:A	K606N	1.000
10:51697732:C:G	K606N	1.000
10:51697736:A:G	L605S	1.000
10:51697742:A:G	L603P	1.000
10:51697745:A:C	I602S	1.000
10:51697745:A:G	I602T	1.000
10:51697745:A:T	I602N	1.000
10:51697769:A:G	L594P	1.000
10:51697769:A:T	L594Q	1.000
10:51697793:A:G	L586P	1.000
10:51697799:A:G	L584P	1.000
10:51697802:A:T	V583D	1.000
10:51697805:T:G	Q582P	1.000
10:51697811:A:C	I580S	1.000
10:51697811:A:G	I580T	1.000
10:51697811:A:T	I580N	1.000
10:51697814:A:C	L579W	1.000
10:51697814:A:G	L579S	1.000
10:51698978:A:G	L191P	1.000
10:51698990:G:T	A187D	1.000
10:51699027:C:G	A175P	1.000
10:51699029:T:G	Q174P	1.000
10:51699032:A:G	L173S	1.000
10:51699035:A:G	L172P	1.000
10:51699035:A:T	L172Q	1.000
10:51699038:G:T	A171E	1.000

dbSNP variants (sampled 300 via entrez): RS1000903918 (10:51697454 T>C,G), RS1000988670 (10:51700404 T>A), RS1001221354 (10:51695443 T>C), RS1001714948 (10:51695199 C>A,T), RS1003268596 (10:51698358 G>A), RS1004894485 (10:51696166 A>G), RS1004954611 (10:51699820 G>A), RS1005690901 (10:51695977 G>A), RS1006369170 (10:51701285 CTT>C), RS1006883167 (10:51699830 G>A), RS1007229921 (10:51700868 A>G), RS1007245838 (10:51695342 CTAAG>C), RS1007275470 (10:51695619 C>T), RS1007400733 (10:51696998 A>C), RS1007624675 (10:51701170 T>C)

Disease associations

OMIM: gene MIM:611968 | disease phenotypes: MIM:615436

GenCC curated gene-disease

Mondo (1): aortic aneurysm, familial thoracic 8 (MONDO:0014187)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002666_2	Interferon alpha levels in systemic lupus erythematosus	3.000000e-08
GCST002668_5	Mammographic density (non-dense area)	3.000000e-06
GCST007006_8	Logical memory (delayed recall) in normal cognition	2.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006517	interferon alpha measurement
EFO:0005941	mammographic density measurement
EFO:0006504	non-dense area measurement
EFO:0004874	memory performance

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
trichostatin A	affects cotreatment, decreases expression	3
Air Pollutants	affects expression, increases abundance, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
manganese chloride	increases abundance, increases expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Cadmium	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Iron	decreases expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression	1
Ozone	affects expression, increases abundance	1
Ribonucleotides	affects binding	1
Silicon Dioxide	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Vitamin D	affects expression	1

Clinical trials (associated diseases)

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