MEX3B

Summary

MEX3B (mex-3 RNA binding family member B, HGNC:25297) is a protein-coding gene on chromosome 15q25.2, encoding RNA-binding protein MEX3B (Q6ZN04). RNA-binding protein.

This gene encodes an RNA-binding phosphoprotein that is part of the MEX3 (muscle excess 3) family of translational regulators. The encoded protein contains N-terminal nuclear export and nuclear localization signals and is exported from the cytoplasm to the nucleus. The protein binds to RNA via two KH domains and also colocalizes with MEX3A, Dcp1A decapping factor and Argonaute proteins within P (processing) bodies.

Source: NCBI Gene 84206 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 96 total
• MANE Select transcript: NM_032246

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25297
Approved symbol	MEX3B
Name	mex-3 RNA binding family member B
Location	15q25.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434J0617, RNF195
Ensembl gene	ENSG00000183496
Ensembl biotype	protein_coding
OMIM	611008
Entrez	84206

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000329713, ENST00000558133

RefSeq mRNA: 1 — MANE Select: NM_032246 NM_032246

CCDS: CCDS10319

Canonical transcript exons

ENST00000329713 — 2 exons

Exon	Start	End
ENSE00001316983	82041778	82044613
ENSE00001418046	82045450	82046018

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 97.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.3084 / max 287.8475, expressed in 1550 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151242	6.8317	1352
151235	0.5080	247
151244	0.2174	87
151243	0.1963	78
151239	0.1712	47
151236	0.1151	45
151240	0.0882	31
151241	0.0750	37
151237	0.0556	17
151238	0.0499	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.98	gold quality
ganglionic eminence	UBERON:0004023	93.63	gold quality
right testis	UBERON:0004534	92.59	gold quality
left testis	UBERON:0004533	92.58	gold quality
cortical plate	UBERON:0005343	92.38	gold quality
testis	UBERON:0000473	89.76	gold quality
ventricular zone	UBERON:0003053	84.79	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.76	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.81	gold quality
stromal cell of endometrium	CL:0002255	76.93	gold quality
endocervix	UBERON:0000458	76.87	gold quality
adult organism	UBERON:0007023	74.14	gold quality
ectocervix	UBERON:0012249	71.89	gold quality
left ovary	UBERON:0002119	71.58	gold quality
body of uterus	UBERON:0009853	71.53	gold quality
uterine cervix	UBERON:0000002	71.09	gold quality
muscle layer of sigmoid colon	UBERON:0035805	69.88	gold quality
right ovary	UBERON:0002118	69.86	gold quality
right hemisphere of cerebellum	UBERON:0014890	69.65	gold quality
cerebellar hemisphere	UBERON:0002245	69.21	gold quality
cerebellar cortex	UBERON:0002129	69.11	gold quality
prefrontal cortex	UBERON:0000451	68.62	gold quality
gall bladder	UBERON:0002110	68.62	gold quality
apex of heart	UBERON:0002098	68.60	gold quality
ovary	UBERON:0000992	68.36	gold quality
cerebellum	UBERON:0002037	67.75	gold quality
endometrium	UBERON:0001295	67.40	gold quality
uterus	UBERON:0000995	67.22	gold quality
heart left ventricle	UBERON:0002084	67.03	gold quality
right coronary artery	UBERON:0001625	66.96	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

184 targeting MEX3B, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3662	99.99	73.82	5684

Literature-anchored findings (GeneRIF, showing 6)

• 14-3-3 exerts combined effects on hMex-3B and acts as a major regulator of the sorting between distinct classes of RNA granules (PMID:18779327)
• Mex3b role in the Runx3 degradation in gastric cancer. (PMID:29417297)
• MEX3B mediates resistance to cancer immunotherapy by binding to the 3’ UTR of HLA-A to destabilize the HLA-A mRNA and thus downregulate HLA-A expression on the surface of tumor cells. (PMID:29496759)
• he suppressed IL-37 secretion caused by a type 2 milieu can enhance Mex3B-mediated TLR3 activation and subsequent TSLP production in nasal epithelial cells and therefore promotes eosinophilic inflammation in patients with eosinophilic chronic rhinosinusitis with nasal polyps. (PMID:31330219)
• MEX3B inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell TGFBR3 mRNA stability. (PMID:36976645)
• Molecular mechanism of specific HLA-A mRNA recognition by the RNA-binding-protein hMEX3B to promote tumor immune escape. (PMID:38326406)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mex3b	ENSDARG00000058369
mus_musculus	Mex3b	ENSMUSG00000057706
rattus_norvegicus	Mex3b	ENSRNOG00000025142

Paralogs (3): MEX3C (ENSG00000176624), MEX3D (ENSG00000181588), MEX3A (ENSG00000254726)

Protein

Protein identifiers

RNA-binding protein MEX3B — Q6ZN04 (reviewed: Q6ZN04)

Alternative names: RING finger and KH domain-containing protein 3, RING finger protein 195

All UniProt accessions (1): Q6ZN04

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein. May be involved in post-transcriptional regulatory mechanisms.

Subcellular location. Nucleus. Cytoplasm. P-body. Cytoplasmic granule.

Tissue specificity. Highest levels found in fetal brain and testis. Detected in the adult intestinal epithelium, specifically in goblet cell at protein level.

Post-translational modifications. Phosphorylation at Ser-462 creates a docking site for 14-3-3, which stabilizes the protein and modulates its ability to bind RNA.

Domain organisation. Binds RNA through its KH domains.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZN04-1	1	yes
Q6ZN04-3	2

RefSeq proteins (1): NP_115622* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR004087	KH_dom	Domain
IPR004088	KH_dom_type_1	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR036612	KH_dom_type_1_sf	Homologous_superfamily
IPR047226	KH-I_MEX3_rpt2	Domain
IPR047227	MEX3	Family
IPR047228	KH-I_MEX3_rpt1	Domain

Pfam: PF00013, PF13920

UniProt features (18 total): region of interest 4, modified residue 3, domain 2, splice variant 2, sequence conflict 2, compositionally biased region 2, chain 1, mutagenesis site 1, zinc finger region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9JNM	X-RAY DIFFRACTION	2.2
9JNL	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZN04-F1	62.96	0.33

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 (3): 4, 288, 462

Mutagenesis-validated functional residues (1):

Position	Phenotype
177	prevents rna binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 190 (showing top): AHRARNT_01, TGGTGCT_MIR29A_MIR29B_MIR29C, PAX4_01, TTTGTAG_MIR520D, TATTATA_MIR374, AP2_Q3, GGGTGGRR_PAX4_03, FREAC3_01, TGCTGAY_UNKNOWN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, ATTCTTT_MIR186, ACATATC_MIR190, GFI1_01, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, LEF1_Q6

GO Biological Process (2): protein phosphorylation (GO:0006468), protein autophosphorylation (GO:0046777)

GO Molecular Function (6): RNA binding (GO:0003723), calcium ion binding (GO:0005509), zinc ion binding (GO:0008270), nucleic acid binding (GO:0003676), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): P-body (GO:0000932), nucleoplasm (GO:0005654), cytosol (GO:0005829), nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
phosphorylation	1
protein modification process	1
protein phosphorylation	1
nucleic acid binding	1
metal ion binding	1
transition metal ion binding	1
cation binding	1
cytoplasmic ribonucleoprotein granule	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1250 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MEX3B	DZIP3	Q86Y13	848
MEX3B	DCP1A	Q9NPI6	808
MEX3B	AGO1	Q9UL18	775
MEX3B	SNUPN	O95149	774
MEX3B	HNRNPK	P61978	714
MEX3B	ATXN1	P54253	694
MEX3B	RUNX3	Q13761	554
MEX3B	AGO2	Q9UKV8	487
MEX3B	MEX3A	A1L020	435
MEX3B	SUZ12	Q15022	431
MEX3B	DAZ1	Q9NQZ3	430
MEX3B	PTBP2	Q9UKA9	414
MEX3B	DACT3	Q96B18	410
MEX3B	TTC9B	Q8N6N2	404
MEX3B	IRGQ	Q8WZA9	400

IntAct

23 interactions, top by confidence:

A	B	Type	Score
ENPP6	SCAMP1	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
MEX3B	UBE2D3	psi-mi:“MI:0915”(physical association)	0.550
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPB41L1	AP3B1	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
USP7	MEX3B	psi-mi:“MI:0407”(direct interaction)	0.440
MEX3B	YWHAE	psi-mi:“MI:0915”(physical association)	0.400
SFN	MEX3B	psi-mi:“MI:0915”(physical association)	0.400
ATP13A2	MEX3B	psi-mi:“MI:0915”(physical association)	0.370
MEX3B	NUDT3	psi-mi:“MI:0915”(physical association)	0.370
SNUPN	MEX3B	psi-mi:“MI:0915”(physical association)	0.370
YWHAH	FOXO6	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PIP4K2A	SAP18	psi-mi:“MI:0914”(association)	0.350
RPS11	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
ZNF800	MED19	psi-mi:“MI:2364”(proximity)	0.270
RAP1GAP	MEX3B	psi-mi:“MI:0915”(physical association)	0.000
UBE2D3	MEX3B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (239): MEX3B (Affinity Capture-MS), MEX3B (Affinity Capture-MS), MEX3B (Affinity Capture-MS), SUZ12 (Affinity Capture-Western), HOTAIR (Affinity Capture-RNA), MEX3B (Affinity Capture-Western), MEX3B (Affinity Capture-RNA), MEX3B (Protein-RNA), HLA-A (Affinity Capture-RNA), MEX3B (Two-hybrid), MEX3B (Two-hybrid), AGO1 (Proximity Label-MS), AGO2 (Proximity Label-MS), AGO3 (Proximity Label-MS), AGO4 (Proximity Label-MS)

ESM2 similar proteins: A1L020, A1L3F4, A7X8B3, A7X8B5, A7X8B7, A7X8B9, A7X8C2, A7X8C4, A7X8C7, A7X8C9, A7X8D2, A7X8D4, A7XW25, O97775, O97776, O97952, O97960, P06401, P10275, P84550, P84551, P89463, Q01JD1, Q05A36, Q0VDT2, Q3UE17, Q5PQQ7, Q5U5Q3, Q69Z36, Q6QT55, Q6ZK57, Q6ZN04, Q71FD5, Q7RTV3, Q7TSJ6, Q7XQN1, Q7XT42, Q84SL2, Q86XN8, Q8BQ89

Diamond homologs: A1E2V0, A1L020, A1L3F4, A5D8Q0, A9JTP3, A9ULZ2, D3ZDI6, E3SCZ8, O08863, O10296, O10324, O14064, O15392, O62640, O70201, O88738, P40629, P41435, P41436, P41437, P41454, P47732, P98170, Q05AK5, Q0WPJ7, Q13489, Q13490, Q28ER3, Q28H51, Q50L39, Q557E7, Q5BKL8, Q5R881, Q5RAH9, Q60989, Q62210, Q69Z36, Q6I6F4, Q6J1J1, Q6NTT6

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	MEX3B	ubiquitination
MEX3B	“down-regulates quantity by destabilization”	SNUPN	polyubiquitination
HOTAIR	“up-regulates activity”	MEX3B	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 23 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
SARS-CoV-1-host interactions	5	39.9×	4e-06
SARS-CoV-1 Infection	5	32.4×	1e-05
SARS-CoV-2-host interactions	5	27.0×	2e-05
SARS-CoV-2 Infection	5	18.3×	9e-05
SARS-CoV Infections	6	15.1×	3e-05
Viral Infection Pathways	7	9.8×	7e-05
Membrane Trafficking	5	8.4×	2e-03
Vesicle-mediated transport	5	7.9×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

96 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	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

224 predictions. Top by Δscore:

Variant	Effect	Δscore
15:82044622:CAGGG:C	acceptor_gain	0.9900
15:82044640:G:GC	acceptor_gain	0.9900
15:82045445:CCTA:C	donor_loss	0.9900
15:82045447:TA:T	donor_loss	0.9900
15:82044626:G:C	acceptor_gain	0.9800
15:82044626:G:GC	acceptor_gain	0.9800
15:82044611:AACC:A	acceptor_loss	0.9700
15:82044612:ACCTA:A	acceptor_loss	0.9700
15:82044613:CCTA:C	acceptor_loss	0.9700
15:82044614:CTA:C	acceptor_loss	0.9700
15:82044615:T:G	acceptor_loss	0.9700
15:82044630:G:T	acceptor_gain	0.9700
15:82045448:A:AC	donor_gain	0.9700
15:82045449:C:CC	donor_gain	0.9700
15:82044629:C:CT	acceptor_gain	0.9600
15:82044610:CAAC:C	acceptor_gain	0.9500
15:82044623:A:T	acceptor_gain	0.9500
15:82045449:CCTTG:C	donor_gain	0.9500
15:82044640:G:C	acceptor_gain	0.9300
15:82044622:C:T	acceptor_gain	0.9100
15:82044609:ACAAC:A	acceptor_gain	0.9000
15:82044610:CAACC:C	acceptor_gain	0.9000
15:82044614:C:CC	acceptor_gain	0.9000
15:82045448:AC:A	donor_gain	0.9000
15:82045449:CC:C	donor_gain	0.9000
15:82044612:AC:A	acceptor_gain	0.8900
15:82044613:CC:C	acceptor_gain	0.8900
15:82044755:C:CA	donor_gain	0.8900
15:82044897:T:C	donor_gain	0.8900
15:82045501:A:AC	donor_gain	0.8900

AlphaMissense

3678 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:82043170:A:C	I567S	1.000
15:82043170:A:G	I567T	1.000
15:82043170:A:T	I567N	1.000
15:82043176:A:C	I565S	1.000
15:82043176:A:G	I565T	1.000
15:82043176:A:T	I565N	1.000
15:82043179:G:T	A564D	1.000
15:82043199:G:C	C557W	1.000
15:82043200:C:A	C557F	1.000
15:82043200:C:G	C557S	1.000
15:82043200:C:T	C557Y	1.000
15:82043201:A:G	C557R	1.000
15:82043201:A:T	C557S	1.000
15:82043208:G:C	C554W	1.000
15:82043209:C:A	C554F	1.000
15:82043209:C:G	C554S	1.000
15:82043209:C:T	C554Y	1.000
15:82043210:A:C	C554G	1.000
15:82043210:A:G	C554R	1.000
15:82043210:A:T	C554S	1.000
15:82043242:G:T	A543D	1.000
15:82043243:C:G	A543P	1.000
15:82043244:G:C	C542W	1.000
15:82043245:C:A	C542F	1.000
15:82043245:C:G	C542S	1.000
15:82043245:C:T	C542Y	1.000
15:82043246:A:G	C542R	1.000
15:82043246:A:T	C542S	1.000
15:82043253:G:C	C539W	1.000
15:82043254:C:A	C539F	1.000

dbSNP variants (sampled 300 via entrez): RS1000524415 (15:82041723 T>G), RS1000819819 (15:82046297 GGA>G), RS1001077648 (15:82044880 G>A,C), RS1001238891 (15:82045121 C>G,T), RS1002087386 (15:82047021 G>A,T), RS1002148219 (15:82042698 C>G,T), RS1002439659 (15:82046877 C>G), RS1002862019 (15:82045197 G>A), RS1002867013 (15:82045631 T>C), RS1003091185 (15:82042392 A>G), RS1003582278 (15:82046024 G>A,T), RS1003610088 (15:82046203 G>A,C), RS1004439831 (15:82047520 T>C,G), RS1004886824 (15:82041310 T>A), RS1004958830 (15:82041563 G>A)

Disease associations

OMIM: gene MIM:611008 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000298_9	Body mass index	7.000000e-06
GCST002401_7	Post-traumatic stress disorder	4.000000e-06
GCST005352_3	Paclitaxel disposition in epithelial ovarian cancer	6.000000e-06
GCST006291_62	Spherical equivalent or myopia (age of diagnosis)	2.000000e-10
GCST006976_60	Macular thickness	4.000000e-10
GCST007277_21	Tourette syndrome	7.000000e-06
GCST008839_116	Height	2.000000e-13
GCST010002_102	Refractive error	3.000000e-27

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004847	age at onset

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, affects cotreatment	6
trichostatin A	decreases expression, affects cotreatment	3
sodium arsenite	decreases expression, increases expression	3
Estradiol	affects expression, affects cotreatment, increases expression, decreases expression	3
methylmercuric chloride	increases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Formaldehyde	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	increases expression	2
bisphenol A	decreases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
titanium dioxide	decreases expression	1
kojic acid	increases expression	1
dimethylselenide	decreases expression, increases expression, increases oxidation	1
tobacco tar	decreases expression	1
manganese chloride	increases abundance, increases expression	1
homosalate	affects cotreatment, decreases expression	1
azoxystrobin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
ICG 001	affects expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
licochalcone B	increases expression	1
picoxystrobin	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3AZ	Abcam HEK293T MEX3B KO	Transformed cell line	Female

Clinical trials (associated diseases)

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