MEAK7

Summary

MEAK7 (MTOR associated protein MEAK7, HGNC:29325) is a protein-coding gene on chromosome 16q24.1, encoding MTOR-associated protein MEAK7 (Q6P9B6). Activates an alternative mTOR signaling through RPS6KB2 activation and EIF4EBP1 repression to regulate cell proliferation and migration.

Involved in several processes, including TOR signaling; positive regulation of protein localization to lysosome; and response to insulin. Located in cytosol; lysosomal membrane; and nuclear lumen.

Source: NCBI Gene 57707 — RefSeq curated summary.

At a glance

• GWAS associations: 22
• Clinical variants (ClinVar): 157 total
• MANE Select transcript: NM_020947

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29325
Approved symbol	MEAK7
Name	MTOR associated protein MEAK7
Location	16q24.1
Locus type	gene with protein product
Status	Approved
Aliases	mEAK-7
Ensembl gene	ENSG00000140950
Ensembl biotype	protein_coding
OMIM	619331
Entrez	57707

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 21 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000343629, ENST00000561807, ENST00000562447, ENST00000565079, ENST00000565701, ENST00000565765, ENST00000566995, ENST00000567321, ENST00000570036, ENST00000899776, ENST00000899777, ENST00000899778, ENST00000899779, ENST00000899780, ENST00000899781, ENST00000899782, ENST00000926571, ENST00000926572, ENST00000926573, ENST00000926574, ENST00000926575, ENST00000926576, ENST00000971298, ENST00000971299, ENST00000971300, ENST00000971301

RefSeq mRNA: 1 — MANE Select: NM_020947 NM_020947

CCDS: CCDS32498

Canonical transcript exons

ENST00000343629 — 8 exons

Exon	Start	End
ENSE00001293118	84476355	84480026
ENSE00001514665	84504601	84504659
ENSE00003486363	84486631	84487059
ENSE00003535735	84482592	84482710
ENSE00003627415	84489278	84489422
ENSE00003642406	84495683	84495913
ENSE00003690700	84480529	84480708
ENSE00003692895	84497934	84498111

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 93.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.1021 / max 88.3843, expressed in 1722 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158348	7.9218	1718
158347	0.0935	28
158350	0.0588	32
158349	0.0280	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	93.28	silver quality
gingival epithelium	UBERON:0001949	86.54	gold quality
squamous epithelium	UBERON:0006914	86.47	gold quality
esophagus mucosa	UBERON:0002469	86.14	gold quality
stromal cell of endometrium	CL:0002255	85.63	gold quality
esophagus squamous epithelium	UBERON:0006920	84.87	gold quality
endothelial cell	CL:0000115	84.48	silver quality
gingiva	UBERON:0001828	83.63	gold quality
epithelium of esophagus	UBERON:0001976	83.00	gold quality
placenta	UBERON:0001987	82.46	gold quality
lower esophagus mucosa	UBERON:0035834	82.35	gold quality
tibia	UBERON:0000979	81.74	gold quality
esophagus	UBERON:0001043	81.50	gold quality
tongue squamous epithelium	UBERON:0006919	81.44	silver quality
islet of Langerhans	UBERON:0000006	81.36	gold quality
vagina	UBERON:0000996	80.88	gold quality
secondary oocyte	CL:0000655	80.68	gold quality
cortical plate	UBERON:0005343	80.68	gold quality
mucosa of transverse colon	UBERON:0004991	79.79	gold quality
uterine cervix	UBERON:0000002	79.65	gold quality
pigmented layer of retina	UBERON:0001782	79.51	gold quality
pancreatic ductal cell	CL:0002079	79.23	gold quality
gall bladder	UBERON:0002110	79.16	gold quality
ganglionic eminence	UBERON:0004023	78.93	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.75	gold quality
parietal pleura	UBERON:0002400	78.67	gold quality
Brodmann (1909) area 23	UBERON:0013554	78.65	gold quality
colonic epithelium	UBERON:0000397	78.45	gold quality
calcaneal tendon	UBERON:0003701	78.41	gold quality
oviduct epithelium	UBERON:0004804	78.37	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.72
E-MTAB-7303	no	702.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

102 targeting MEAK7, 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-150-5P	99.99	66.69	1976
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085

Literature-anchored findings (GeneRIF, showing 3)

• miR325p suppresses the proliferation and migration of pancreatic adenocarcinoma cells by targeting TLDC1. (PMID:34468015)
• Molecular basis of mEAK7-mediated human V-ATPase regulation. (PMID:35672408)
• Identification of mEAK-7 as a human V-ATPase regulator via cryo-EM data mining. (PMID:35994636)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	meak7	ENSDARG00000062951
mus_musculus	Meak7	ENSMUSG00000034105
rattus_norvegicus	Meak7	ENSRNOG00000016224
drosophila_melanogaster	CG5149	FBGN0031904
caenorhabditis_elegans		WBGENE00010671

Paralogs (3): TLDC2 (ENSG00000101342), NCOA7 (ENSG00000111912), OXR1 (ENSG00000164830)

Protein

Protein identifiers

MTOR-associated protein MEAK7 — Q6P9B6 (reviewed: Q6P9B6)

Alternative names: MTOR associated protein, eak-7 homolog, TBC/LysM-associated domain-containing protein 1, TLD domain-containing protein 1

All UniProt accessions (6): Q6P9B6, H3BM75, H3BPI4, H3BQ13, H3BTC5, H3BUB0

UniProt curated annotations — full annotation on UniProt →

Function. Activates an alternative mTOR signaling through RPS6KB2 activation and EIF4EBP1 repression to regulate cell proliferation and migration. Recruits MTOR at the lysosome, essential for MTOR signaling at the lysosome.

Subunit / interactions. Interacts (via C-terminal domain) with MTOR and MLST8; the interaction with MTOR increases upon nutrient stimulation.

Subcellular location. Membrane. Cytoplasm. Lysosome.

Induction. Addition of nutrients and insulin induces its expression (at protein level).

RefSeq proteins (1): NP_065998* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006571	TLDc_dom	Domain

Pfam: PF07534

UniProt features (12 total): sequence variant 7, initiator methionine 1, chain 1, mutagenesis site 1, domain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7U4T	ELECTRON MICROSCOPY	3.6
7UNE	ELECTRON MICROSCOPY	3.73
7UNF	ELECTRON MICROSCOPY	4.08

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P9B6-F1	86.73	0.71

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 (1): 2

Mutagenesis-validated functional residues (1):

Position	Phenotype
2	abolishes lysosomal location.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 156 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOCC_VACUOLAR_MEMBRANE, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, MODULE_453, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_OXIDATIVE_STRESS, GOBP_PROTEIN_LOCALIZATION_TO_LYSOSOME, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, MODULE_205, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, KESHELAVA_MULTIPLE_DRUG_RESISTANCE, GOBP_RESPONSE_TO_INSULIN, GOBP_PROTEIN_LOCALIZATION_TO_VACUOLE, FISCHER_G2_M_CELL_CYCLE

GO Biological Process (9): response to oxidative stress (GO:0006979), regulation of cell migration (GO:0030334), response to nutrient levels (GO:0031667), TOR signaling (GO:0031929), response to insulin (GO:0032868), regulation of cell population proliferation (GO:0042127), response to amino acid (GO:0043200), positive regulation of protein localization to lysosome (GO:0150032), negative regulation of cellular response to oxidative stress (GO:1900408)

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

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), cytosol (GO:0005829), membrane (GO:0016020), lysosome (GO:0005764)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
nuclear lumen	2
response to stress	1
cell migration	1
regulation of cell motility	1
response to stimulus	1
intracellular signal transduction	1
response to peptide hormone	1
cell population proliferation	1
regulation of cellular process	1
response to acid chemical	1
protein localization to lysosome	1
regulation of protein localization to lysosome	1
positive regulation of protein localization	1
cellular response to oxidative stress	1
negative regulation of cellular process	1
regulation of cellular response to oxidative stress	1
negative regulation of response to oxidative stress	1
binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
lysosome	1
lytic vacuole membrane	1
cytoplasm	1
lytic vacuole	1

Protein interactions and networks

STRING

404 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MEAK7	CCDC182	A6NF36	496
MEAK7	GOLGA7B	Q2TAP0	491
MEAK7	DHX32	Q7L7V1	488
MEAK7	RWDD2A	Q9UIY3	466
MEAK7	TDRKH	Q9Y2W6	456
MEAK7	ARHGAP22	Q7Z5H3	449
MEAK7	ART3	Q13508	447
MEAK7	STK36	Q9NRP7	446
MEAK7	MXRA8	Q9BRK3	443
MEAK7	RNASEK	Q6P5S7	440
MEAK7	TBC1D24	Q9ULP9	434
MEAK7	C22orf39	Q6P5X5	433
MEAK7	DHX37	Q8IY37	430
MEAK7	CCDC85C	A6NKD9	421
MEAK7	AGFG1	P52594	408

IntAct

25 interactions, top by confidence:

A	B	Type	Score
MEAK7	TRIP13	psi-mi:“MI:0915”(physical association)	0.710
TRIP13	MEAK7	psi-mi:“MI:0915”(physical association)	0.710
MEAK7	NMT2	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
SHARPIN	MAP3K7	psi-mi:“MI:0914”(association)	0.350
TANK	CNOT1	psi-mi:“MI:0914”(association)	0.350
TNIP2	TMEM178B	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
ARRDC5	PLPP1	psi-mi:“MI:0914”(association)	0.350
CERS2	VPS37C	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
KRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
HRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (55): TLDC1 (Affinity Capture-MS), TLDC1 (Affinity Capture-MS), TLDC1 (Affinity Capture-MS), TLDC1 (Affinity Capture-MS), TLDC1 (Affinity Capture-MS), TLDC1 (Affinity Capture-MS), TLDC1 (Two-hybrid), GMFB (Co-fractionation), TLDC1 (Co-fractionation), TLDC1 (Affinity Capture-MS), TLDC1 (Affinity Capture-MS), NMT1 (Affinity Capture-MS), NMT2 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), TLDC1 (Affinity Capture-RNA)

ESM2 similar proteins: A2VE39, B1H268, D2HRF1, E1BSI0, F1MX48, O00763, O14730, O54935, O88554, O95801, P26446, P42898, P47897, Q1RMT7, Q28DH9, Q2KIJ6, Q2YD98, Q3MHH4, Q3ULW8, Q4V7A9, Q5I598, Q5R981, Q5RHR0, Q5U2Q4, Q5U2Z5, Q60596, Q66H61, Q6DDX8, Q6MG55, Q6P9B6, Q7TMM8, Q810A5, Q8BML9, Q8K0P3, Q8N1G2, Q8N5Y8, Q8N6R0, Q91WR3, Q99PL6, Q9CZT4

Diamond homologs: A0PJX2, A2ACG1, A5PKL1, A8KBE0, B4F6Q9, O14284, Q08952, Q0IID2, Q1LWV7, Q3UUG6, Q4KMM3, Q4V8B0, Q5ZJX5, Q5ZMS4, Q6C443, Q6CMK8, Q6DDZ9, Q6DFV7, Q6FSN5, Q6P9B6, Q755A3, Q874Z5, Q8K0P3, Q8N573, Q8NI08, Q9ULP9, Q9VIH7, P0CP42, P0CP43, Q6ZZF5, Q7S4P1, A1A5K6, Q29RJ2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	120
Likely benign	11
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

2211 predictions. Top by Δscore:

Variant	Effect	Δscore
16:84479883:T:TA	donor_gain	1.0000
16:84479932:T:TA	donor_gain	1.0000
16:84479933:C:A	donor_gain	1.0000
16:84480365:T:TA	donor_gain	1.0000
16:84482590:A:AC	donor_gain	1.0000
16:84482591:C:CC	donor_gain	1.0000
16:84482722:C:CT	acceptor_gain	1.0000
16:84482722:C:T	acceptor_gain	1.0000
16:84495914:C:CC	acceptor_gain	1.0000
16:84495918:C:CT	acceptor_gain	1.0000
16:84497926:A:AC	donor_gain	1.0000
16:84497927:C:CC	donor_gain	1.0000
16:84497927:CT:C	donor_gain	1.0000
16:84497986:T:C	donor_gain	1.0000
16:84498108:TTCT:T	acceptor_gain	1.0000
16:84498110:CT:C	acceptor_gain	1.0000
16:84504596:CCTA:C	donor_loss	1.0000
16:84504597:CTA:C	donor_loss	1.0000
16:84504598:TA:T	donor_loss	1.0000
16:84504599:AC:A	donor_gain	1.0000
16:84504600:CC:C	donor_gain	1.0000
16:84504600:CCCTG:C	donor_gain	1.0000
16:84480028:T:C	acceptor_gain	0.9900
16:84480336:TAAAC:T	donor_gain	0.9900
16:84480528:CCAA:C	donor_gain	0.9900
16:84482585:GGCT:G	donor_loss	0.9900
16:84482586:GCT:G	donor_loss	0.9900
16:84482587:CTC:C	donor_loss	0.9900
16:84482589:C:CG	donor_loss	0.9900
16:84482590:A:C	donor_loss	0.9900

AlphaMissense

3020 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:84486635:A:C	F318L	0.997
16:84486635:A:T	F318L	0.997
16:84486637:A:G	F318L	0.997
16:84486655:A:G	W312R	0.997
16:84486655:A:T	W312R	0.997
16:84480643:G:C	S381R	0.996
16:84480643:G:T	S381R	0.996
16:84480645:T:G	S381R	0.996
16:84480561:A:G	W409R	0.995
16:84480561:A:T	W409R	0.995
16:84480610:G:C	S392R	0.994
16:84480610:G:T	S392R	0.994
16:84480612:T:G	S392R	0.994
16:84480625:G:C	C387W	0.993
16:84480682:A:C	F368L	0.993
16:84480682:A:T	F368L	0.993
16:84480684:A:G	F368L	0.993
16:84486677:G:C	F304L	0.993
16:84486677:G:T	F304L	0.993
16:84486679:A:G	F304L	0.993
16:84486779:A:C	F270L	0.993
16:84486779:A:T	F270L	0.993
16:84486781:A:G	F270L	0.993
16:84480618:A:C	Y390D	0.992
16:84480675:A:G	W371R	0.992
16:84480675:A:T	W371R	0.992
16:84480702:C:A	G362W	0.992
16:84480559:C:A	W409C	0.991
16:84480559:C:G	W409C	0.991
16:84480701:C:T	G362E	0.991

dbSNP variants (sampled 300 via entrez): RS1000054319 (16:84503292 G>A), RS1000130190 (16:84497657 A>C), RS1000185260 (16:84506222 T>C), RS1000239932 (16:84482439 A>C,G), RS1000273711 (16:84484117 G>A,C,T), RS1000477498 (16:84493831 G>A,C), RS1000593301 (16:84493619 C>T), RS1000619632 (16:84487593 G>A,C), RS1000834140 (16:84477444 G>T), RS1000890209 (16:84504366 G>T), RS1000952091 (16:84500740 G>A), RS1000955332 (16:84504169 T>C), RS1000955826 (16:84480327 C>A,T), RS1001091617 (16:84480139 G>C,T), RS1001113508 (16:84483423 G>T)

Disease associations

OMIM: gene MIM:619331 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST003876_12	Gut microbiota (beta diversity)	5.000000e-08
GCST004610_147	White blood cell count	4.000000e-25
GCST004613_48	Sum neutrophil eosinophil counts	5.000000e-12
GCST004614_25	Granulocyte count	3.000000e-12
GCST004620_96	Sum basophil neutrophil counts	8.000000e-12
GCST004625_158	Monocyte count	1.000000e-16
GCST004626_136	Myeloid white cell count	1.000000e-13
GCST004627_162	Lymphocyte count	2.000000e-23
GCST004629_146	Neutrophil count	1.000000e-11
GCST005652_8	Cleft lip with or without cleft palate (maternal periconceptional vitamin use interaction)	6.000000e-06
GCST006976_101	Macular thickness	2.000000e-13
GCST008399_6	Cocaine dependence	9.000000e-06
GCST009391_342	Metabolite levels	6.000000e-06
GCST90002379_177	Basophil count	1.000000e-10
GCST90002388_174	Lymphocyte count	6.000000e-46
GCST90002391_80	Mean corpuscular hemoglobin concentration	3.000000e-12
GCST90002393_274	Monocyte count	2.000000e-37
GCST90002395_227	Mean platelet volume	4.000000e-14
GCST90002397_250	Mean spheric corpuscular volume	5.000000e-21
GCST90002398_302	Neutrophil count	7.000000e-13
GCST90002400_185	Plateletcrit	2.000000e-12
GCST90002407_561	White blood cell count	2.000000e-37

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0004587	lymphocyte count
EFO:0003959	cleft lip
EFO:0009116	vitamin supplement exposure measurement
EFO:0010433	triacylglycerol 56:6 measurement
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
FR900359	increases phosphorylation	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
jinfukang	increases expression	1
Arsenic Trioxide	increases expression	1
Leflunomide	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Furaldehyde	affects cotreatment, affects localization, decreases expression	1
Ivermectin	decreases expression	1
Methotrexate	decreases expression	1
Progesterone	increases expression	1
Silicon Dioxide	increases expression	1
Smoke	increases expression	1
Sodium Chloride	affects cotreatment, affects localization, decreases expression, increases expression	1
Thimerosal	decreases expression	1
Tobacco Smoke Pollution	affects expression	1

Clinical trials (associated diseases)

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