SNAP47

Summary

SNAP47 (synaptosome associated protein 47, HGNC:30669) is a protein-coding gene on chromosome 1q42.13, encoding Synaptosomal-associated protein 47 (Q5SQN1). Plays a role in intracellular membrane fusion.

Predicted to enable SNAP receptor activity and syntaxin binding activity. Predicted to be involved in synaptic vesicle fusion to presynaptic active zone membrane and synaptic vesicle priming. Predicted to act upstream of or within long-term synaptic potentiation. Located in BLOC-1 complex.

Source: NCBI Gene 116841 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 94 total
• MANE Select transcript: NM_053052

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30669
Approved symbol	SNAP47
Name	synaptosome associated protein 47
Location	1q42.13
Locus type	gene with protein product
Status	Approved
Aliases	SVAP1, SNAP-47
Ensembl gene	ENSG00000143740
Ensembl biotype	protein_coding
OMIM	619659
Entrez	116841

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 37 protein_coding, 7 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000315781, ENST00000366759, ENST00000366760, ENST00000418653, ENST00000426344, ENST00000470038, ENST00000475930, ENST00000478768, ENST00000480265, ENST00000480897, ENST00000491439, ENST00000606873, ENST00000617596, ENST00000679561, ENST00000679575, ENST00000680202, ENST00000680695, ENST00000680854, ENST00000680992, ENST00000681006, ENST00000681149, ENST00000681242, ENST00000681252, ENST00000681447, ENST00000681465, ENST00000681554, ENST00000681678, ENST00000681685, ENST00000681827, ENST00000681929, ENST00000857367, ENST00000857368, ENST00000857369, ENST00000857370, ENST00000857371, ENST00000857372, ENST00000857373, ENST00000857374, ENST00000928311, ENST00000928312, ENST00000972178, ENST00000972179, ENST00000972180, ENST00000972181, ENST00000972182

RefSeq mRNA: 7 — MANE Select: NM_053052 NM_001323930, NM_001323931, NM_001323932, NM_001323933, NM_001323934, NM_001323935, NM_053052

CCDS: CCDS81429

Canonical transcript exons

ENST00000617596 — 5 exons

Exon	Start	End
ENSE00001442552	227780527	227781226
ENSE00003664029	227758995	227759485
ENSE00003719098	227766959	227767083
ENSE00003731794	227747692	227748233
ENSE00003742491	227735435	227735499

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 96.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.0167 / max 86.1217, expressed in 1796 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8903	12.7251	1786
8901	1.5774	755
8902	0.3592	196
8904	0.3550	129

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	96.23	gold quality
prefrontal cortex	UBERON:0000451	94.10	gold quality
left adrenal gland cortex	UBERON:0035825	94.10	gold quality
apex of heart	UBERON:0002098	93.87	gold quality
right frontal lobe	UBERON:0002810	93.74	gold quality
nucleus accumbens	UBERON:0001882	93.68	gold quality
left adrenal gland	UBERON:0001234	93.57	gold quality
middle temporal gyrus	UBERON:0002771	93.50	gold quality
left ovary	UBERON:0002119	93.48	gold quality
adrenal cortex	UBERON:0001235	93.26	gold quality
anterior cingulate cortex	UBERON:0009835	93.17	gold quality
right ovary	UBERON:0002118	93.16	gold quality
putamen	UBERON:0001874	93.11	gold quality
right adrenal gland cortex	UBERON:0035827	93.11	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.96	gold quality
right adrenal gland	UBERON:0001233	92.95	gold quality
tibialis anterior	UBERON:0001385	92.88	silver quality
caudate nucleus	UBERON:0001873	92.78	gold quality
cortical plate	UBERON:0005343	92.74	gold quality
neocortex	UBERON:0001950	92.58	gold quality
frontal cortex	UBERON:0001870	92.54	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.54	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.41	gold quality
primary visual cortex	UBERON:0002436	92.14	gold quality
left testis	UBERON:0004533	92.08	gold quality
adrenal gland	UBERON:0002369	92.06	gold quality
right testis	UBERON:0004534	91.61	gold quality
cerebral cortex	UBERON:0000956	91.55	gold quality
amygdala	UBERON:0001876	91.50	gold quality
ovary	UBERON:0000992	91.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-112	yes	8.03
E-ANND-3	yes	4.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting SNAP47, 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-4487	99.96	64.58	1252
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-609	99.82	64.26	505
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-548AT-3P	98.37	64.98	580
HSA-MIR-548AY-3P	98.37	65.14	562
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-4523	85.64	61.16	64

Literature-anchored findings (GeneRIF, showing 4)

• Three proteins are identified: PAI-RBP1, C1orf142, and COTL1, which are differentially expressed in non-small cell lung cancer cell lines with different metastatic potential. (PMID:22373659)
• SNAP47 Interacts with ATG14 to Promote VP1 Conjugation and CVB3 Propagation. (PMID:34440910)
• A novel identified circular RNA, circSnap47, promotes heart failure progression via regulation of miR-223-3p/MAPK axis. (PMID:35900666)
• The STX17-SNAP47-VAMP7/VAMP8 complex is the default SNARE complex mediating autophagosome-lysosome fusion. (PMID:38182888)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	snap47	ENSDARG00000063445
mus_musculus	Snap47	ENSMUSG00000009894
rattus_norvegicus	Snap47	ENSRNOG00000022472

Paralogs (3): SNAP23 (ENSG00000092531), SNAP29 (ENSG00000099940), SNAP25 (ENSG00000132639)

Protein

Protein identifiers

Synaptosomal-associated protein 47 — Q5SQN1 (reviewed: Q5SQN1)

Alternative names: Epididymis luminal protein 170, Synaptosomal-associated 47 kDa protein

All UniProt accessions (11): Q5SQN1, A0A087X0B7, A0A087X2J6, A0A7P0T899, A0A7P0T8U4, A0A7P0T9T2, A0A7P0TBK4, A0A7P0Z4P6, H0Y627, H7C3C7, U3KPT7

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in intracellular membrane fusion.

Subunit / interactions. Forms a complex containing SNAP47, VAMP2 and STX1A. Associates with the BLOC-1 complex. Interacts with BLOC1S6.

Subcellular location. Endomembrane system. Cytoplasm. Perinuclear region.

Similarity. Belongs to the SVAP1 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5SQN1-1	1	yes
Q5SQN1-2	2
Q5SQN1-3	3
Q5SQN1-4	4

RefSeq proteins (7): NP_001310859, NP_001310860, NP_001310861, NP_001310862, NP_001310863, NP_001310864, NP_444280* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000727	T_SNARE_dom	Domain
IPR004182	GRAM	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily

Pfam: PF02893

UniProt features (11 total): sequence variant 4, domain 2, splice variant 2, chain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5SQN1-F1	70.80	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 183 (showing top): GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, GOBP_MEMBRANE_FUSION, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MACROAUTOPHAGY, GOBP_CELL_CELL_SIGNALING, GOBP_EXOCYTOSIS, GOBP_VESICLE_FUSION_TO_PLASMA_MEMBRANE, GOBP_ORGANELLE_MEMBRANE_FUSION, MODULE_206, GOBP_SECRETION, GOBP_SIGNAL_RELEASE, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN

GO Biological Process (6): exocytosis (GO:0006887), synaptic vesicle priming (GO:0016082), synaptic vesicle fusion to presynaptic active zone membrane (GO:0031629), long-term synaptic potentiation (GO:0060291), exocytic insertion of neurotransmitter receptor to postsynaptic membrane (GO:0098967), vesicle-mediated transport in synapse (GO:0099003)

GO Molecular Function (3): SNAP receptor activity (GO:0005484), syntaxin binding (GO:0019905), protein binding (GO:0005515)

GO Cellular Component (16): plasma membrane (GO:0005886), endomembrane system (GO:0012505), SNARE complex (GO:0031201), perinuclear region of cytoplasm (GO:0048471), presynapse (GO:0098793), cytoplasm (GO:0005737), postsynaptic density (GO:0014069), membrane (GO:0016020), dendrite (GO:0030425), BLOC-1 complex (GO:0031083), asymmetric synapse (GO:0032279), neuronal cell body (GO:0043025), synapse (GO:0045202), presynaptic active zone (GO:0048786), hippocampal mossy fiber to CA3 synapse (GO:0098686), glutamatergic synapse (GO:0098978)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
synapse	3
vesicle-mediated transport	2
vesicle fusion to plasma membrane	2
synaptic vesicle exocytosis	2
cytoplasm	2
neuron to neuron synapse	2
secretion by cell	1
protein-containing complex assembly	1
exocytic process	1
synaptic vesicle membrane organization	1
regulation of synaptic plasticity	1
positive regulation of synaptic transmission	1
exocytosis	1
neurotransmitter receptor transport to postsynaptic membrane	1
regulation of postsynaptic membrane neurotransmitter receptor levels	1
protein-macromolecule adaptor activity	1
membrane fusion	1
fusogenic activity	1
SNARE binding	1
binding	1
membrane	1
cell periphery	1
vacuole	1
plasma membrane	1
membrane protein complex	1
intracellular anatomical structure	1
asymmetric synapse	1
postsynaptic specialization	1
neuron projection	1
dendritic tree	1
BLOC complex	1
postsynaptic density	1
somatodendritic compartment	1
cell body	1
cell junction	1
presynapse	1
thorny excrescence	1
hippocampal mossy fiber expansion	1

Protein interactions and networks

STRING

1348 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNAP47	SNAP29	O95721	818
SNAP47	VAMP2	P19065	812
SNAP47	STX3	Q13277	797
SNAP47	SNAP23	O00161	717
SNAP47	STX1A	Q16623	713
SNAP47	YKT6	O15498	676
SNAP47	STX4	Q12846	661
SNAP47	SYT2	Q8N9I0	617
SNAP47	VAMP7	P51809	595
SNAP47	AOC3	Q16853	591
SNAP47	SNAP25	P13795	536
SNAP47	TRIM67	Q6ZTA4	522
SNAP47	VAMP4	O75379	518
SNAP47	STX16	O14662	507
SNAP47	JMJD4	Q9H9V9	501

IntAct

160 interactions, top by confidence:

A	B	Type	Score
Stx1a	Stxbp1	psi-mi:“MI:0914”(association)	0.920
STX18	NBAS	psi-mi:“MI:0914”(association)	0.810
STX12	SNAP47	psi-mi:“MI:0915”(physical association)	0.740
FAM9C	SNAP29	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FAM9C	NDC80	psi-mi:“MI:0914”(association)	0.670
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
STX7	SNAP23	psi-mi:“MI:0914”(association)	0.640
STX12	SNAP23	psi-mi:“MI:0914”(association)	0.640
MAGEA6	SNAP47	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	SNAP47	psi-mi:“MI:0915”(physical association)	0.560
STX4	SNAP47	psi-mi:“MI:0915”(physical association)	0.560
KLC3	SNAP47	psi-mi:“MI:0915”(physical association)	0.560
CEP57L1	SNAP47	psi-mi:“MI:0915”(physical association)	0.560
SNAP47	FAM9B	psi-mi:“MI:0915”(physical association)	0.560
SNAP47	FATE1	psi-mi:“MI:0915”(physical association)	0.560
SPAG5	SNAP47	psi-mi:“MI:0915”(physical association)	0.560
SNAP47	MID2	psi-mi:“MI:0915”(physical association)	0.560
SNAP47	GOLGA2	psi-mi:“MI:0915”(physical association)	0.560
SNAP47	CEP57L1	psi-mi:“MI:0915”(physical association)	0.560
FATE1	SNAP47	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (213): SNAP47 (Two-hybrid), SNAP47 (Two-hybrid), SNAP47 (Two-hybrid), SNAP47 (Two-hybrid), SNAP47 (Two-hybrid), SNAP47 (Two-hybrid), KLC3 (Two-hybrid), FAM9B (Two-hybrid), CEP57L1 (Two-hybrid), SNAP47 (Affinity Capture-MS), SNAP47 (Affinity Capture-MS), SNAP47 (Affinity Capture-MS), SNAP47 (Affinity Capture-MS), SNAP47 (Affinity Capture-MS), SNAP47 (Affinity Capture-MS)

ESM2 similar proteins: A2BID5, A4D1P6, A5WW21, A6QP11, B2RYI0, E9PUQ8, E9PXF8, O14976, O15068, P0CI65, P32019, P57075, P70600, P97874, Q008S8, Q0P4A7, Q0V9N0, Q14289, Q16760, Q2HJE1, Q2I6J0, Q3U213, Q5FVC7, Q5R6T6, Q5SQN1, Q5SVR0, Q5ZK62, Q5ZLL7, Q5ZLR6, Q63406, Q64096, Q66K14, Q6IVG4, Q6NTN5, Q6P6S0, Q6TEN6, Q6ZQK5, Q7TMQ7, Q7TT49, Q7TT50

Diamond homologs: A6QP11, Q0P4A7, Q5SQN1, Q6P6S0, Q8R570

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 115 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
Intra-Golgi traffic	5	19.4×	2e-04
trans-Golgi Network Vesicle Budding	5	18.9×	2e-04
Intra-Golgi and retrograde Golgi-to-ER traffic	9	14.1×	4e-06
COPII-mediated vesicle transport	5	12.2×	6e-04
Golgi-to-ER retrograde transport	6	11.9×	2e-04
COPI-dependent Golgi-to-ER retrograde traffic	7	11.6×	8e-05
ER-Phagosome pathway	5	9.7×	1e-03
Cargo recognition for clathrin-mediated endocytosis	5	7.8×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
vesicle fusion	10	62.0×	2e-13
obsolete vesicle docking	7	55.3×	9e-09
membrane fusion	5	32.2×	5e-05
Golgi to plasma membrane protein transport	5	27.1×	9e-05
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	5	17.4×	6e-04
exocytosis	8	12.5×	3e-05
cellular response to type II interferon	5	10.7×	4e-03
intracellular protein transport	13	8.7×	7e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2354 predictions. Top by Δscore:

Variant	Effect	Δscore
1:227732675:ACC:A	acceptor_loss	1.0000
1:227732677:C:CC	acceptor_gain	1.0000
1:227733023:TCATC:T	acceptor_gain	1.0000
1:227733024:CATC:C	acceptor_gain	1.0000
1:227733024:CATCC:C	acceptor_gain	1.0000
1:227733025:ATCCT:A	acceptor_loss	1.0000
1:227733026:TC:T	acceptor_gain	1.0000
1:227733026:TCCTG:T	acceptor_loss	1.0000
1:227733027:CC:C	acceptor_gain	1.0000
1:227733028:C:A	acceptor_loss	1.0000
1:227733028:C:CC	acceptor_gain	1.0000
1:227733029:T:A	acceptor_loss	1.0000
1:227733408:CATTA:C	donor_loss	1.0000
1:227733409:ATTAC:A	donor_loss	1.0000
1:227733410:TTAC:T	donor_loss	1.0000
1:227733411:TACCA:T	donor_loss	1.0000
1:227733412:A:C	donor_loss	1.0000
1:227733469:T:TA	donor_gain	1.0000
1:227733642:CCAG:C	acceptor_gain	1.0000
1:227733643:CAGC:C	acceptor_gain	1.0000
1:227733901:CCTCA:C	donor_loss	1.0000
1:227733902:CTCA:C	donor_loss	1.0000
1:227733905:A:AC	donor_gain	1.0000
1:227733905:ACCAG:A	donor_loss	1.0000
1:227733906:C:CC	donor_gain	1.0000
1:227733906:CCAG:C	donor_gain	1.0000
1:227734721:T:A	donor_gain	1.0000
1:227734977:T:A	donor_gain	1.0000
1:227735015:AGGT:A	donor_gain	1.0000
1:227735024:G:C	donor_gain	1.0000

AlphaMissense

2744 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:227747975:T:C	F125S	0.992
1:227747800:T:A	W67R	0.985
1:227747800:T:C	W67R	0.985
1:227759213:T:A	I284K	0.984
1:227759300:T:A	I313N	0.984
1:227747842:T:C	F81L	0.983
1:227747844:C:A	F81L	0.983
1:227747844:C:G	F81L	0.983
1:227747764:T:A	W55R	0.981
1:227747764:T:C	W55R	0.981
1:227747802:G:C	W67C	0.980
1:227747802:G:T	W67C	0.980
1:227747843:T:C	F81S	0.980
1:227759357:T:G	M332R	0.980
1:227747776:T:G	Y59D	0.977
1:227759213:T:G	I284R	0.975
1:227759357:T:A	M332K	0.974
1:227748025:T:C	F142L	0.973
1:227748027:C:A	F142L	0.973
1:227748027:C:G	F142L	0.973
1:227759186:T:C	L275P	0.972
1:227759270:T:A	I303N	0.970
1:227747929:T:C	F110L	0.969
1:227747931:C:A	F110L	0.969
1:227747931:C:G	F110L	0.969
1:227747977:A:C	S126R	0.969
1:227747979:C:A	S126R	0.969
1:227747979:C:G	S126R	0.969
1:227759192:T:A	V277D	0.969
1:227747816:T:C	L72P	0.968

dbSNP variants (sampled 300 via entrez): RS1000063862 (1:227779384 G>A), RS1000114768 (1:227765252 A>G), RS1000119087 (1:227765460 A>G), RS1000195863 (1:227765942 T>G), RS1000199559 (1:227767934 C>T), RS1000252452 (1:227765000 G>A), RS1000272274 (1:227736405 C>A), RS1000462676 (1:227763943 G>C), RS1000483316 (1:227768210 A>C,T), RS1000489218 (1:227749149 C>T), RS1000541743 (1:227758119 C>T), RS1000598162 (1:227763728 T>C), RS1000628627 (1:227746578 G>C), RS1000713555 (1:227752477 G>A), RS1000727486 (1:227773437 A>T)

Disease associations

OMIM: gene MIM:619659 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST003542_210	Night sleep phenotypes	7.000000e-06
GCST008163_362	Height	2.000000e-09
GCST012227_1221	Hip circumference adjusted for BMI	2.000000e-09
GCST90020025_1288	Waist-to-hip ratio adjusted for BMI	5.000000e-08
GCST90020027_1588	Waist-hip index	4.000000e-09
GCST90020028_419	Hip circumference adjusted for BMI	4.000000e-08
GCST90020029_635	Waist circumference adjusted for body mass index	3.000000e-09
GCST90020029_636	Waist circumference adjusted for body mass index	8.000000e-13
GCST90020029_637	Waist circumference adjusted for body mass index	3.000000e-13
GCST90020029_638	Waist circumference adjusted for body mass index	8.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference
EFO:0007788	BMI-adjusted waist-hip ratio
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

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
Cisplatin	affects cotreatment, increases expression, decreases expression, decreases response to substance	2
alpha-pinene	affects cotreatment, affects expression, increases abundance	1
pirinixic acid	increases activity, affects binding, decreases expression	1
aflatoxin B2	increases methylation	1
methacrylaldehyde	increases abundance, affects cotreatment, affects expression	1
jinfukang	affects cotreatment, increases expression	1
Arsenic Trioxide	decreases expression	1
Leflunomide	decreases expression	1
Acrolein	affects cotreatment, affects expression, increases abundance	1
Air Pollutants	affects cotreatment, affects expression, increases abundance	1
Ozone	affects cotreatment, affects expression, increases abundance	1
Smoke	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Volatile Organic Compounds	affects cotreatment, affects expression	1

Clinical trials (associated diseases)

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