VNN1

Summary

VNN1 (vanin 1, HGNC:12705) is a protein-coding gene on chromosome 6q23.2, encoding Pantetheinase (O95497). Amidohydrolase that hydrolyzes specifically one of the carboamide linkages in D-pantetheine thus recycling pantothenic acid (vitamin B5) and releasing cysteamine.

This gene encodes a member of the vanin family of proteins, which share extensive sequence similarity with each other, and also with biotinidase. The family includes secreted and membrane-associated proteins, a few of which have been reported to participate in hematopoietic cell trafficking. No biotinidase activity has been demonstrated for any of the vanin proteins, however, they possess pantetheinase activity, which may play a role in oxidative-stress response. This protein, like its mouse homolog, is likely a GPI-anchored cell surface molecule. The mouse protein is expressed by the perivascular thymic stromal cells and regulates migration of T-cell progenitors to the thymus. This gene lies in close proximity to, and in the same transcriptional orientation as, two other vanin genes on chromosome 6q23-q24.

Source: NCBI Gene 8876 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 82 total
• Druggable target: yes
• MANE Select transcript: NM_004666

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12705
Approved symbol	VNN1
Name	vanin 1
Location	6q23.2
Locus type	gene with protein product
Status	Approved
Aliases	Tiff66
Ensembl gene	ENSG00000112299
Ensembl biotype	protein_coding
OMIM	603570
Entrez	8876

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000367928, ENST00000886805, ENST00000886806, ENST00000886807, ENST00000886808

RefSeq mRNA: 1 — MANE Select: NM_004666 NM_004666

CCDS: CCDS5159

Canonical transcript exons

ENST00000367928 — 7 exons

Exon	Start	End
ENSE00000764052	132684335	132684505
ENSE00000764053	132692223	132692584
ENSE00000764054	132693024	132693315
ENSE00001445946	132680849	132683322
ENSE00001445947	132713826	132714055
ENSE00002450880	132693990	132694182
ENSE00002459486	132711709	132711839

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 99.78.

FANTOM5 (CAGE): breadth broad, TPM avg 5.1706 / max 858.5559, expressed in 424 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75611	4.5459	277
75609	0.5000	160
75608	0.0905	35
75607	0.0190	6
75610	0.0152	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.78	gold quality
duodenum	UBERON:0002114	96.71	gold quality
gall bladder	UBERON:0002110	95.00	gold quality
liver	UBERON:0002107	93.36	gold quality
right lobe of liver	UBERON:0001114	92.57	gold quality
epithelial cell of pancreas	CL:0000083	91.65	gold quality
nephron tubule	UBERON:0001231	89.68	gold quality
blood	UBERON:0000178	87.59	gold quality
pancreatic ductal cell	CL:0002079	86.68	gold quality
ileal mucosa	UBERON:0000331	85.73	gold quality
kidney epithelium	UBERON:0004819	85.64	gold quality
bone marrow	UBERON:0002371	85.44	gold quality
trabecular bone tissue	UBERON:0002483	83.66	gold quality
monocyte	CL:0000576	83.63	gold quality
renal glomerulus	UBERON:0000074	83.39	gold quality
mononuclear cell	CL:0000842	83.15	gold quality
leukocyte	CL:0000738	82.58	gold quality
metanephric glomerulus	UBERON:0004736	82.55	gold quality
bone marrow cell	CL:0002092	80.76	gold quality
endometrium	UBERON:0001295	79.44	gold quality
small intestine	UBERON:0002108	77.21	gold quality
jejunum	UBERON:0002115	77.16	gold quality
islet of Langerhans	UBERON:0000006	77.01	gold quality
bronchial epithelial cell	CL:0002328	76.99	gold quality
epithelium of bronchus	UBERON:0002031	75.68	gold quality
adult mammalian kidney	UBERON:0000082	75.43	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.19	gold quality
epithelium of nasopharynx	UBERON:0001951	74.59	gold quality
bronchus	UBERON:0002185	74.44	gold quality
kidney	UBERON:0002113	74.37	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-83139	yes	551.49
E-ENAD-27	yes	6.97
E-ANND-3	yes	5.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A, NR5A1, SOX8, SOX9

miRNA regulators (miRDB)

103 targeting VNN1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-548P	99.98	72.25	3784
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-548AZ-5P	99.83	69.94	3230

Literature-anchored findings (GeneRIF, showing 30)

• Pantetheinase (Vnn1) is critical for the host susceptibility to malaria. (PMID:17312006)
• missense SNP rs2272996 (or N131S) in the VNN1 gene was significantly associated with hypertension in African Americans and the association was replicated in Mexican Americans; a non-significant opposite association was observed in European Americans (PMID:18043751)
• vanin-1 and vanin-3 are induced at the mRNA and protein level by psoriasis-associated proinflammatory cytokines (Th17/Th1) but not by Th2 cytokines. (PMID:19322213)
• The combination of VNN1 and MMP9 may be used as a novel blood biomarker panel for the discrimination of pancreatic cancer-associated diabetes from type 2 diabetes. (PMID:20571492)
• Overexpression of VNN1, an oxidative stress sensor in epithelial cells, was most strongly associated with progression to chronic immune thrombocytopenia (PMID:21325602)
• Urinary vanin-1, an ectoenzyme pantetheinase, distinguished diabetic patients with macroalbuminuria from those with normal albuminuria. (PMID:21544065)
• data do not support a major role for the Vanin 1 T26I variant in determining blood pressure level and incident ischemic events (PMID:21550219)
• Vanin-1 is a specific and sensitive biomarker for renal tubular injury induced by organic solvents. (PMID:21907259)
• Our data suggest that VNN1 gene expression and the G-137T variant are associated with HDL-C levels in Mexican children, particularly in prepubertal girls. (PMID:23185446)
• Our results suggest that vanin-1 can distinguish between chronic responders and non-responders ITP patients as well as between newly diagnosed ITP patients and healthy controls. (PMID:23534352)
• Single-nucleotide polymorphisms in the Regulatory Regions of the VNN1 Gene Are Associated with inflammatory bowel diseases. (PMID:23949622)
• It isthe enzyme that recycles pantothenic acid (vitamin B5) generated during coenzyme A breakdown and actively involved in the progression of inflammatory reactions by generating cysteamine. (PMID:23978960)
• Microparticle internalization required the interaction of the ectoenzyme Vanin-1 (VNN1), an abundant surface protein on the microparticles, with lipid raft domains of endothelial cells. (PMID:24106341)
• Liver contributes to Vanin-1 secretion in serum and PPARalpha is a limiting factor in serum Vnn1 production. (PMID:24140347)
• Alternative Splicing in VNN1 gene is associated with colorectal cancer. (PMID:24687856)
• Serum vanin-1 levels may be low in the end-stage renal failure and transiently increase after transplant owing to transient renal function deterioration, which does not lead to elevation of serum creatinine levels in renal transplant patients. (PMID:24702142)
• show that hepatic vanin-1 is under extremely sensitive regulation by PPARalpha and that plasma vanin activity could serve as a readout of changes in PPARalpha activity in human subjects (PMID:24751833)
• Our study provides strong biological evidence for the association of the identified SNP with BP and suggests that vanin-1 misfolding and degradation are the underlying molecular mechanism. (PMID:25233454)
• The X-ray crystal structure of human vanin 1 at 2.25 A resolution is presented, which is the first reported structure from the vanin family, as well as a crystal structure of vanin 1 bound to a specific inhibitor. (PMID:25478849)
• VNN1 contributes to corticosteroid responsiveness, and changes in VNN1 nasal epithelial mRNA expression and VNN1 promoter methylation might be clinically useful biomarkers of treatment response in asthmatic children. (PMID:25910714)
• serum pantetheinas, encoded by the VNN1 gene, level regulates erythrocyte life span and modulates the risk of developing complicated malaria. (PMID:26343328)
• These data suggest that urinary vanin-1 is an early predictive biomarker for decline in eGFR in patients with urothelial carcinoma after dosing of cisplatin (PMID:27317936)
• Data show that G protein-coupled receptor, family C, group 5, member A protein (GPRC5A) regulates oxidative stress through vanin 1 protein (VNN1). (PMID:28316092)
• findings suggest that the metabolic pathway catalyzed by VNN1 pantetheinase plays a suppressive role in IAV infection in the respiratory tract, especially in severe conditions under hypercytokinemia (PMID:28576495)
• Urinary vanin-1 is a useful biomarker to detect and monitor the clinical course of obstructive nephropathy. (PMID:30791405)
• This review discusses the role of vanin 1 in the liver, kidney, intestine, and lung under physiological as well as pathophysiological conditions. [review] (PMID:31404995)
• Urinary vanin-1 for predicting acute pyelonephritis in young children with urinary tract infection: a pilot study. (PMID:33656956)
• Pancreatic ductal deletion of S100A9 alleviates acute pancreatitis by targeting VNN1-mediated ROS release to inhibit NLRP3 activation. (PMID:33754072)
• Near-Infrared Fluorescent Probe for Imaging and Evaluating the Role of Vanin-1 in Chemotherapy. (PMID:34275284)
• Urinary vanin-1 as a novel biomarker for survival in peripheral artery disease. (PMID:38607943)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Vnn1	ENSMUSG00000037440
rattus_norvegicus	Vnn1	ENSRNOG00000016219
drosophila_melanogaster	Btnd	FBGN0029848
drosophila_melanogaster	vanin-like	FBGN0040069
drosophila_melanogaster	CG32750	FBGN0052750
drosophila_melanogaster	CG32751	FBGN0052751

Paralogs (2): VNN2 (ENSG00000112303), BTD (ENSG00000169814)

Protein

Protein identifiers

Pantetheinase — O95497 (reviewed: O95497)

Alternative names: Pantetheine hydrolase, Tiff66, Vascular non-inflammatory molecule 1

All UniProt accessions (1): O95497

UniProt curated annotations — full annotation on UniProt →

Function. Amidohydrolase that hydrolyzes specifically one of the carboamide linkages in D-pantetheine thus recycling pantothenic acid (vitamin B5) and releasing cysteamine.

Subunit / interactions. Monomer.

Subcellular location. Cell membrane.

Tissue specificity. Widely expressed with higher expression in spleen, kidney and blood. Overexpressed in lesional psoriatic skin.

Induction. By Th17/Th1 type cytokines, but not by Th2-type.

Similarity. Belongs to the carbon-nitrogen hydrolase superfamily. BTD/VNN family.

RefSeq proteins (1): NP_004657* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003010	C-N_Hydrolase	Domain
IPR012101	Biotinidase-like_euk	Family
IPR036526	C-N_Hydrolase_sf	Homologous_superfamily
IPR040154	Biotinidase/VNN	Family
IPR043957	Vanin_C	Domain

Pfam: PF00795, PF19018

Enzyme classification (BRENDA):

• EC 3.5.1.92 — pantetheine hydrolase (BRENDA: 6 organisms, 31 substrates, 43 inhibitors, 6 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PANTOTHENATE-7-AMIDO-4-METHYLCOUMARIN	13–28	2
(R)-PANTETHEINE	0.02	1
PANTETHEINE	5	1
S-CYSTEAMINE-3-PYRUVATE	—	1

Catalyzed reactions (Rhea), 1 shown:

• (R)-pantetheine + H2O = cysteamine + (R)-pantothenate (RHEA:13445)

UniProt features (71 total): strand 25, helix 12, sequence variant 9, glycosylation site 6, turn 6, sequence conflict 3, active site 3, mutagenesis site 2, signal peptide 1, chain 1, propeptide 1, domain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7SLV	X-RAY DIFFRACTION	2.13
7SLY	X-RAY DIFFRACTION	2.17
4CYF	X-RAY DIFFRACTION	2.25
9IZL	X-RAY DIFFRACTION	2.28
4CYG	X-RAY DIFFRACTION	2.3
7SLX	X-RAY DIFFRACTION	2.35
4CYY	X-RAY DIFFRACTION	2.89

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95497-F1	92.68	0.89

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 79 (proton acceptor); 178 (proton donor); 211 (nucleophile)

Post-translational modifications (1): 491

Glycosylation sites (6): 200, 283, 315, 353, 38, 130

Mutagenesis-validated functional residues (2):

Position	Phenotype
79	abolishes enzyme activity.
178	abolishes enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins
R-HSA-199220	Vitamin B5 (pantothenate) metabolism
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 260 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, MODULE_255, GOBP_INFLAMMATORY_RESPONSE, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_COENZYME_A_METABOLIC_PROCESS, MODULE_317, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GRAHAM_CML_QUIESCENT_VS_NORMAL_QUIESCENT_DN, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS

GO Biological Process (10): acute inflammatory response (GO:0002526), chronic inflammatory response (GO:0002544), inflammatory response (GO:0006954), response to oxidative stress (GO:0006979), coenzyme A catabolic process (GO:0015938), pantothenate metabolic process (GO:0015939), positive regulation of T cell differentiation in thymus (GO:0033089), innate immune response (GO:0045087), cell-cell adhesion (GO:0098609), positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway (GO:1902177)

GO Molecular Function (3): pantetheine hydrolase activity (GO:0017159), hydrolase activity (GO:0016787), hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides (GO:0016811)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), membrane (GO:0016020), azurophil granule membrane (GO:0035577), side of membrane (GO:0098552)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Post-translational protein modification	1
Metabolism of water-soluble vitamins and cofactors	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
inflammatory response	2
membrane	2
defense response	1
response to stress	1
coenzyme A metabolic process	1
sulfur compound catabolic process	1
purine-containing compound catabolic process	1
nucleoside phosphate catabolic process	1
modified amino acid metabolic process	1
monocarboxylic acid metabolic process	1
T cell differentiation in thymus	1
regulation of T cell differentiation in thymus	1
positive regulation of T cell differentiation	1
immune response	1
defense response to symbiont	1
cell adhesion	1
intrinsic apoptotic signaling pathway in response to oxidative stress	1
regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	1
positive regulation of intrinsic apoptotic signaling pathway	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
catalytic activity	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	1
cell periphery	1
lysosomal membrane	1
secretory granule membrane	1
azurophil granule	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

1536 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VNN1	SERPINE2	P07093	770
VNN1	SRY	Q05066	637
VNN1	PRRG4	Q9BZD6	572
VNN1	TAAR2	Q9P1P5	521
VNN1	TAAR5	O14804	493
VNN1	STX7	O15400	474
VNN1	TAAR1	Q96RJ0	448
VNN1	CEBPA	P49715	443
VNN1	CLEC4D	Q8WXI8	438
VNN1	PCTP	Q9UKL6	437
VNN1	MYL1	P05976	436
VNN1	LPIN2	Q92539	425
VNN1	G0S2	P27469	414
VNN1	TAAR6	Q96RI8	402
VNN1	ANXA3	P12429	399

IntAct

2 interactions, top by confidence:

A	B	Type	Score
VNN1	SMAD7	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): VNN1 (Synthetic Lethality), COX18 (Affinity Capture-MS), SMAD7 (Affinity Capture-MS), XRCC1 (Affinity Capture-MS), SEMA3C (Affinity Capture-MS), DHFRL1 (Affinity Capture-MS), VNN3 (Affinity Capture-MS), PCOLCE2 (Affinity Capture-MS), TMEM205 (Affinity Capture-MS), VNN1 (Positive Genetic)

ESM2 similar proteins: A5PJN5, A6QQ07, B2RXS4, O08590, O15031, O35632, O95497, O95498, P09172, P14616, P15101, P19801, P26011, P36633, P43251, P83548, Q3SZL5, Q3V5L5, Q4R7M2, Q58CQ9, Q5FVF9, Q5R8R3, Q5XI31, Q64237, Q64716, Q6PD26, Q765H6, Q76HN1, Q8AV84, Q8BG22, Q8CIF4, Q8IRR1, Q8JZQ5, Q8NFI3, Q8SQG7, Q91ZJ9, Q9BDJ5, Q9DA79, Q9DBX3, Q9H3S1

Diamond homologs: A6QQ07, C6KYS2, O95497, O95498, P43251, Q58CQ9, Q5FVF9, Q8AV84, Q8CIF4, Q9BDJ5, Q9QZ25, Q9TSX8, Q9Z0K8, P83548, Q9UYV8, Q8IRR1, Q9NFP1, P49954

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	6
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

990 predictions. Top by Δscore:

Variant	Effect	Δscore
6:132684460:C:CT	acceptor_gain	1.0000
6:132684501:CAAAT:C	acceptor_gain	1.0000
6:132692217:TATTA:T	donor_loss	1.0000
6:132692218:ATTAC:A	donor_loss	1.0000
6:132692219:TTA:T	donor_loss	1.0000
6:132692220:TA:T	donor_loss	1.0000
6:132692222:C:CA	donor_loss	1.0000
6:132692581:CTTC:C	acceptor_gain	1.0000
6:132693238:T:TA	donor_gain	1.0000
6:132693311:TTTTG:T	acceptor_gain	1.0000
6:132693312:TTTG:T	acceptor_gain	1.0000
6:132693313:TTG:T	acceptor_gain	1.0000
6:132693314:TG:T	acceptor_gain	1.0000
6:132693315:GC:G	acceptor_loss	1.0000
6:132693316:C:A	acceptor_loss	1.0000
6:132693316:C:CC	acceptor_gain	1.0000
6:132693984:TTTTA:T	donor_loss	1.0000
6:132693985:TTTA:T	donor_loss	1.0000
6:132693986:TTACC:T	donor_loss	1.0000
6:132693987:TACC:T	donor_loss	1.0000
6:132693988:ACCT:A	donor_loss	1.0000
6:132694189:CA:C	acceptor_gain	1.0000
6:132694190:A:C	acceptor_gain	1.0000
6:132694192:G:GC	acceptor_gain	1.0000
6:132694194:T:C	acceptor_gain	1.0000
6:132694194:T:TC	acceptor_gain	1.0000
6:132694197:T:TC	acceptor_gain	1.0000
6:132692355:T:A	donor_gain	0.9900
6:132692412:AAATT:A	donor_gain	0.9900
6:132692416:T:TA	donor_gain	0.9900

AlphaMissense

3375 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:132693990:C:A	K178N	0.999
6:132693990:C:G	K178N	0.999
6:132693991:T:G	K178T	0.995
6:132692580:A:C	S277R	0.992
6:132692580:A:T	S277R	0.992
6:132692582:T:G	S277R	0.992
6:132693090:A:G	W254R	0.992
6:132693090:A:T	W254R	0.992
6:132693138:A:G	W238R	0.992
6:132693138:A:T	W238R	0.992
6:132694149:G:C	S125R	0.992
6:132694149:G:T	S125R	0.992
6:132694151:T:G	S125R	0.992
6:132693136:C:A	W238C	0.991
6:132693136:C:G	W238C	0.991
6:132693991:T:A	K178M	0.991
6:132693217:G:C	C211W	0.989
6:132693992:T:C	K178E	0.989
6:132694000:C:G	R175P	0.988
6:132694141:G:T	A128D	0.986
6:132693214:A:C	F212L	0.985
6:132693214:A:T	F212L	0.985
6:132693216:A:G	F212L	0.985
6:132694004:C:G	A174P	0.985
6:132693992:T:G	K178Q	0.984
6:132694110:A:C	N138K	0.984
6:132694110:A:T	N138K	0.984
6:132713954:C:G	A28P	0.984
6:132693052:G:C	N266K	0.983
6:132693052:G:T	N266K	0.983

dbSNP variants (sampled 300 via entrez): RS1000100142 (6:132691606 T>C), RS1000131598 (6:132691858 A>G), RS1000204424 (6:132688847 C>T), RS1000244707 (6:132696694 C>A,G), RS1000249320 (6:132691546 G>A), RS1000322579 (6:132680927 T>C), RS1000469506 (6:132696491 G>T), RS1000564689 (6:132701408 G>A), RS1000583177 (6:132692598 G>A), RS1000597363 (6:132695915 T>A), RS1000687436 (6:132706409 G>C,T), RS1000790099 (6:132687586 C>A,G), RS1000828504 (6:132682816 T>A), RS1000961907 (6:132682624 G>C), RS1000999107 (6:132697839 A>G)

Disease associations

OMIM: gene MIM:603570 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4739843 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Hydrolases & Lipases

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
example 25 [WO2018228934]	Inhibition	10.0	pIC50
larubrilstat	Inhibition	8.62	pIC50
vanin-1 inhibitor [PMID: 33196323]	Inhibition	8.47	pIC50

Binding affinities (BindingDB)

198 measured of 206 human assays (206 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[(3S)-1-(spiro[3,5-dihydro-2H-pyrido[3,2-b][1,4]oxazepine-4,1’-cyclopropane]-8-carbonyl)pyrrolidin-3-yl]pyrrolidin-2-one	IC50	0.1 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
3-[(3S)-1-(spiro[3,5-dihydro-2H-pyrido[3,2-b][1,4]oxazepine-4,1’-cyclopropane]-8-carbonyl)pyrrolidin-3-yl]-1,3-oxazolidin-2-one	IC50	0.2 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
N-methyl-N-[(3S)-1-(spiro[3,5-dihydro-2H-pyrido[3,2-b][1,4]oxazepine-4,1’-cyclopropane]-8-carbonyl)pyrrolidin-3-yl]acetamide	IC50	0.2 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
(3-pyridin-4-ylpyrrolidin-1-yl)-spiro[2,4-dihydropyrido[3,2-b][1,4]oxazine-3,1’-cyclopropane]-7-ylmethanone	IC50	0.4 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
N-methyl-N-[(3S)-1-(spiro[2,4-dihydropyrido[3,2-b][1,4]oxazine-3,1’-cyclopropane]-7-carbonyl)pyrrolidin-3-yl]acetamide	IC50	0.4 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
[2-(pyridin-3-ylmethylamino)pyrimidin-5-yl]-[3-(trifluoromethyl)phenyl]methanone	IC50	0.5 nM	US-10308615: Heterocyclic compounds as inhibitors of Vanin-1 enzyme
N-[(3S)-1-(3,3-dimethyl-2,4-dihydropyrido[3,2-b][1,4]oxazine-7-carbonyl)pyrrolidin-3-yl]-N-methylacetamide	IC50	0.5 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
3-[(3S)-1-(spiro[2,4-dihydropyrido[3,2-b][1,4]oxazine-3,1’-cyclopropane]-7-carbonyl)pyrrolidin-3-yl]-1,3-oxazolidin-2-one	IC50	0.6 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
(5S)-1-methyl-7-(spiro[3,5-dihydro-2H-pyrido[3,2-b][1,4]oxazepine-4,1’-cyclopropane]-8-carbonyl)-1,7-diazaspiro[4.4]nonan-2-one	IC50	0.6 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
1-[(3S)-1-(spiro[2,4-dihydropyrido[3,2-b][1,4]oxazine-3,1’-cyclopropane]-7-carbonyl)pyrrolidin-3-yl]pyrrolidin-2-one	IC50	0.7 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
N-methyl-N-[(3S)-1-(spiro[2,4-dihydropyrido[3,2-b][1,4]oxazine-3,1’-cyclopropane]-7-carbonyl)pyrrolidin-3-yl]cyclopropanecarboxamide	IC50	0.7 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
(3-methylsulfonylphenyl)-[2-[(1-pyrimidin-5-ylcyclopropyl)amino]pyrimidin-5-yl]methanone	IC50	0.8 nM	US-10308615: Heterocyclic compounds as inhibitors of Vanin-1 enzyme
N-methyl-N-[(3S)-1-(spiro[2,4-dihydropyrido[3,2-b][1,4]oxazine-3,1’-cyclopropane]-7-carbonyl)pyrrolidin-3-yl]oxetane-3-carboxamide	IC50	0.9 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
1-methyl-7-(spiro[3,5-dihydro-2H-pyrido[3,2-b][1,4]oxazepine-4,1’-cyclopropane]-8-carbonyl)-1,7-diazaspiro[4.4]nonan-2-one	IC50	1.09 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
N-[(3S)-1-(3,3-dimethyl-4,5-dihydro-2H-pyrido[3,2-b][1,4]oxazepine-8-carbonyl)pyrrolidin-3-yl]-N-methylacetamide	IC50	1.1 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
[2-[(6-methyl-3-pyridinyl)methylamino]pyrimidin-5-yl]-[3-(trifluoromethyl)phenyl]methanone	IC50	1.2 nM	US-10308615: Heterocyclic compounds as inhibitors of Vanin-1 enzyme
N-[(3S)-1-[(3S)-3-ethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-7-carbonyl]pyrrolidin-3-yl]-N-methylacetamide	IC50	1.3 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
N-methyl-N-[(3S)-1-[(2R)-2-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-7-carbonyl]pyrrolidin-3-yl]acetamide	IC50	1.3 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
[3-(1H-pyrazol-5-yl)pyrrolidin-1-yl]-[2-[(1-pyrimidin-5-ylcyclopropyl)amino]pyrimidin-5-yl]methanone	IC50	1.35 nM	US-10906888: Pyrimidine carboxamides as inhibitors of Vanin-1 enzyme
N-methyl-N-[(3S)-1-[(3S)-3-propan-2-yl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-7-carbonyl]pyrrolidin-3-yl]acetamide	IC50	1.5 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
[2-[(1-pyrimidin-5-ylcyclopropyl)amino]pyrimidin-5-yl]-[3-(trifluoromethyl)phenyl]methanone	IC50	1.7 nM	US-10308615: Heterocyclic compounds as inhibitors of Vanin-1 enzyme
[(3S)-3-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl]-(3-pyridin-4-ylpyrrolidin-1-yl)methanone	IC50	1.7 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
N-methyl-N-[(3S)-1-(2,3,4,5-tetrahydropyrido[3,2-b][1,4]oxazepine-8-carbonyl)pyrrolidin-3-yl]acetamide	IC50	1.7 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
[(3S)-3-phenyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl]-(3-pyridin-4-ylpyrrolidin-1-yl)methanone	IC50	1.8 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
N-methyl-N-[(3S)-1-[(3S)-3-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-7-carbonyl]pyrrolidin-3-yl]acetamide	IC50	1.8 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
[3-(5-methyl-1H-pyrazol-3-yl)pyrrolidin-1-yl]-[2-[(1-pyrimidin-5-ylcyclopropyl)amino]pyrimidin-5-yl]methanone	IC50	1.82 nM	US-10906888: Pyrimidine carboxamides as inhibitors of Vanin-1 enzyme
(3-methylsulfonylphenyl)-[2-(pyridin-3-ylmethylamino)pyrimidin-5-yl]methanone	IC50	2 nM	US-10308615: Heterocyclic compounds as inhibitors of Vanin-1 enzyme
3-[2-[(1-pyridin-3-ylcyclopropyl)amino]pyrimidine-5-carbonyl]benzonitrile	IC50	2.1 nM	US-10308615: Heterocyclic compounds as inhibitors of Vanin-1 enzyme
N-methyl-N-[(3S)-1-(spiro[2,4-dihydropyrido[3,2-b][1,4]oxazine-3,1’-cyclopropane]-7-carbonyl)pyrrolidin-3-yl]cyclopropanesulfonamide	IC50	2.3 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
[(3S)-3-propan-2-yl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl]-(3-pyridin-4-ylpyrrolidin-1-yl)methanone	IC50	2.4 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
N-methyl-N-[(3S)-1-[(3S)-3-phenyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-7-carbonyl]pyrrolidin-3-yl]acetamide	IC50	2.4 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
[(2R)-2-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl]-(3-pyridin-4-ylpyrrolidin-1-yl)methanone	IC50	2.5 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
N-[(3S)-1-[(2S)-2-(hydroxymethyl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-7-carbonyl]pyrrolidin-3-yl]-N-methylacetamide	IC50	2.5 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
[(3S)-3-ethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl]-(3-pyridin-4-ylpyrrolidin-1-yl)methanone	IC50	3.1 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
N-[(3S)-1-[(3R)-3-ethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-7-carbonyl]pyrrolidin-3-yl]-N-methylacetamide	IC50	3.3 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
N-methyl-N-[(3S)-1-[(3R)-3-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-7-carbonyl]pyrrolidin-3-yl]acetamide	IC50	3.3 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
3-[2-[(1-pyrazin-2-ylcyclopropyl)amino]pyrimidine-5-carbonyl]benzonitrile	IC50	3.4 nM	US-10308615: Heterocyclic compounds as inhibitors of Vanin-1 enzyme
[4-fluoro-3-(trifluoromethyl)phenyl]-[2-(pyridin-3-ylmethylamino)pyrimidin-5-yl]methanone	IC50	3.4 nM	US-10308615: Heterocyclic compounds as inhibitors of Vanin-1 enzyme
[(2S)-2-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl]-(3-pyridin-4-ylpyrrolidin-1-yl)methanone	IC50	3.5 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
N-methyl-N-[(3S)-1-[(3R)-3-propan-2-yl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-7-carbonyl]pyrrolidin-3-yl]acetamide	IC50	3.6 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
[(2S)-2-(hydroxymethyl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl]-(3-pyridin-4-ylpyrrolidin-1-yl)methanone	IC50	3.7 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
[(3R)-3-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl]-(3-pyridin-3-ylpyrrolidin-1-yl)methanone	IC50	3.8 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
3-[2-(1-pyridin-3-ylethylamino)pyrimidine-5-carbonyl]benzonitrile	IC50	3.9 nM	US-10308615: Heterocyclic compounds as inhibitors of Vanin-1 enzyme
3-[2-[(1-pyrimidin-5-ylcyclopropyl)amino]pyrimidine-5-carbonyl]benzonitrile	IC50	4.1 nM	US-10308615: Heterocyclic compounds as inhibitors of Vanin-1 enzyme
[2-(pyrazin-2-ylmethylamino)pyrimidin-5-yl]-[3-(trifluoromethyl)phenyl]methanone	IC50	6.4 nM	US-10308615: Heterocyclic compounds as inhibitors of Vanin-1 enzyme
(5R)-1-methyl-7-(spiro[3,5-dihydro-2H-pyrido[3,2-b][1,4]oxazepine-4,1’-cyclopropane]-8-carbonyl)-1,7-diazaspiro[4.4]nonan-2-one	IC50	8.1 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
N-[(3S)-1-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-7-carbonyl)pyrrolidin-3-yl]-N-methylacetamide	IC50	8.1 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
[(3R)-3-ethyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl]-(3-pyridin-4-ylpyrrolidin-1-yl)methanone	IC50	8.9 nM	US-10364255: Heteroaromatic compounds as Vanin inhibitors
4-[(1R)-1-[[5-(3-cyanobenzoyl)pyrimidin-2-yl]amino]ethyl]benzamide	IC50	10.3 nM	US-10308615: Heterocyclic compounds as inhibitors of Vanin-1 enzyme
[2-[(1-phenylcyclopropyl)amino]pyrimidin-5-yl]-[3-(trifluoromethyl)phenyl]methanone	IC50	10.6 nM	US-10308615: Heterocyclic compounds as inhibitors of Vanin-1 enzyme

ChEMBL bioactivities

662 potent at pChembl≥5 of 672 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.40	IC50	0.04	nM	CHEMBL5084938
10.40	IC50	0.04	nM	CHEMBL5089503
10.37	IC50	0.043	nM	CHEMBL5089503
10.22	IC50	0.06	nM	CHEMBL5085625
10.21	IC50	0.062	nM	CHEMBL5085625
10.10	IC50	0.08	nM	CHEMBL5082540
10.09	IC50	0.082	nM	CHEMBL5082540
9.96	IC50	0.11	nM	CHEMBL5072128
9.94	IC50	0.116	nM	CHEMBL5087511
9.92	IC50	0.12	nM	CHEMBL5087511
9.71	IC50	0.196	nM	CHEMBL5905017
9.70	IC50	0.2	nM	CHEMBL6051964
9.62	IC50	0.24	nM	CHEMBL5088348
9.62	IC50	0.242	nM	CHEMBL5088348
9.62	IC50	0.24	nM	CHEMBL6035635
9.56	IC50	0.277	nM	CHEMBL5087956
9.55	IC50	0.28	nM	CHEMBL5087956
9.55	IC50	0.283	nM	CHEMBL5846706
9.55	IC50	0.283	nM	CHEMBL5810596
9.53	IC50	0.293	nM	CHEMBL5883652
9.52	IC50	0.3	nM	CHEMBL6002225
9.52	IC50	0.3	nM	CHEMBL5840158
9.52	IC50	0.3	nM	CHEMBL5928597
9.52	IC50	0.3	nM	CHEMBL6022228
9.52	IC50	0.3	nM	CHEMBL6059546
9.52	IC50	0.3	nM	CHEMBL5765592
9.52	IC50	0.3	nM	CHEMBL5941530
9.46	IC50	0.35	nM	CHEMBL5081075
9.46	IC50	0.349	nM	CHEMBL5081075
9.40	IC50	0.4	nM	CHEMBL5969571
9.40	IC50	0.4	nM	CHEMBL5944189
9.40	IC50	0.4	nM	CHEMBL5773927
9.40	IC50	0.4	nM	CHEMBL6064642
9.40	IC50	0.4	nM	CHEMBL5744524
9.40	IC50	0.4	nM	CHEMBL5973759
9.40	IC50	0.4	nM	CHEMBL5960254
9.40	IC50	0.4	nM	CHEMBL5850386
9.37	IC50	0.43	nM	CHEMBL5092354
9.30	IC50	0.5	nM	CHEMBL5893875
9.30	IC50	0.504	nM	CHEMBL5780061
9.30	IC50	0.504	nM	CHEMBL5948148
9.30	IC50	0.5	nM	CHEMBL5974083
9.26	IC50	0.551	nM	CHEMBL5841268
9.23	IC50	0.582	nM	CHEMBL5984700
9.22	IC50	0.6	nM	CHEMBL5083289
9.20	IC50	0.629	nM	CHEMBL5964276
9.19	IC50	0.65	nM	CHEMBL5083289
9.17	IC50	0.68	nM	CHEMBL5082701
9.17	IC50	0.677	nM	CHEMBL5082701
9.15	IC50	0.7	nM	CHEMBL5834685

PubChem BioAssay actives

68 with measured affinity, of 78 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
8-oxa-2-azaspiro[4.5]decan-2-yl-[2-[(1-pyrazin-2-ylcyclobutyl)amino]pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	<0.0001	uM
7-oxa-2-azaspiro[3.5]nonan-2-yl-[2-[(1-pyrazin-2-ylcyclobutyl)amino]pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	<0.0001	uM
7-oxa-2-azaspiro[3.5]nonan-2-yl-[2-(2-pyrazin-2-ylpropan-2-ylamino)pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0001	uM
8-oxa-2-azaspiro[4.5]decan-2-yl-[2-(2-pyrazin-2-ylpropan-2-ylamino)pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0001	uM
8-oxa-2-azaspiro[4.5]decan-2-yl-[2-(2-pyrimidin-5-ylpropan-2-ylamino)pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0001	uM
8-oxa-2-azaspiro[4.5]decan-2-yl-[2-[(1-pyrimidin-5-ylcyclobutyl)amino]pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0001	uM
8-oxa-2-azaspiro[4.5]decan-2-yl-[2-[[(1S)-1-pyrazin-2-ylethyl]amino]pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0002	uM
8-oxa-2-azaspiro[4.5]decan-2-yl-[2-[(1-pyrimidin-5-ylcyclopropyl)amino]pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0003	uM
8-oxa-2-azaspiro[4.5]decan-2-yl-[2-[(3-pyrazin-2-yloxetan-3-yl)amino]pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0003	uM
8-oxa-2-azaspiro[4.5]decan-2-yl-[2-[(3-pyrimidin-5-yloxetan-3-yl)amino]pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0004	uM
7-oxa-2-azaspiro[3.5]nonan-2-yl-[2-[[(1S)-1-pyrazin-2-ylethyl]amino]pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0006	uM
8-oxa-2-azaspiro[4.5]decan-2-yl-[2-[[(1S)-1-pyrimidin-5-ylethyl]amino]pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0007	uM
8-oxa-2-azaspiro[4.5]decan-2-yl-[2-(pyridin-3-ylmethylamino)pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0013	uM
8-oxa-2-azaspiro[4.5]decan-2-yl-[2-[[(1R)-1-pyrazin-2-ylethyl]amino]pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0031	uM
7-oxa-2-azaspiro[3.5]nonan-2-yl-[2-(pyrazin-2-ylmethylamino)pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0034	uM
3-[2-[(1-pyrimidin-5-ylcyclopropyl)amino]pyrimidine-5-carbonyl]benzonitrile	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0041	uM
3-[2-(pyridin-3-ylmethylamino)pyrimidine-5-carbonyl]benzonitrile	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0044	uM
8-oxa-2-azaspiro[4.5]decan-2-yl-[2-(pyrazin-2-ylmethylamino)pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0069	uM
1-[2-[(1-pyrimidin-5-ylcyclopropyl)amino]pyrimidine-5-carbonyl]piperidine-3-carbonitrile	1824883: Binding affinity to recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells assessed as dissociation constant by surface plasmon resonance analysis	kd	0.0072	uM
8-oxa-2-azaspiro[4.5]decan-2-yl-[2-(pyrimidin-5-ylmethylamino)pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0077	uM
[(3R)-3-methylsulfonylpiperidin-1-yl]-[2-[(1-pyrimidin-5-ylcyclopropyl)amino]pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0106	uM
piperidin-1-yl-[2-[(1-pyrimidin-5-ylcyclopropyl)amino]pyrimidin-5-yl]methanone	1824865: Inhibition of human plasma vanin-1 using pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition	ic50	0.0123	uM
3-[2-[(1-phenylcyclopropyl)amino]pyrimidine-5-carbonyl]benzonitrile	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0220	uM
8-oxa-2-azaspiro[4.5]decan-2-yl-[2-[[(1R)-1-pyrimidin-5-ylethyl]amino]pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0279	uM
3-[2-(pyrimidin-5-ylmethylamino)pyrimidine-5-carbonyl]benzonitrile	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0330	uM
(3-methylsulfonylpiperidin-1-yl)-[2-[(1-pyrimidin-5-ylcyclopropyl)amino]pyrimidin-5-yl]methanone	1824883: Binding affinity to recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells assessed as dissociation constant by surface plasmon resonance analysis	kd	0.0370	uM
(2R)-2,4-dihydroxy-3,3-dimethyl-N-[3-oxo-4-[4-(trifluoromethoxy)phenyl]butyl]butanamide	1892118: Inhibition of human serum vanin-1 using pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 10 mins followed by substrate addition by fluorometry	ic50	0.0380	uM
(3-methylphenyl)-[2-(pyridin-3-ylmethylamino)pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0520	uM
(3R)-1-[2-[(1-pyrimidin-5-ylcyclopropyl)amino]pyrimidine-5-carbonyl]piperidine-3-carbonitrile	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0520	uM
phenyl-[2-(pyridin-3-ylmethylamino)pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0530	uM
3-[2-(benzylamino)pyrimidine-5-carbonyl]benzonitrile	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.0800	uM
(2R)-N-[4-(4-fluorophenyl)-3-oxobutyl]-2,4-dihydroxy-3,3-dimethylbutanamide	1892118: Inhibition of human serum vanin-1 using pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 10 mins followed by substrate addition by fluorometry	ic50	0.1000	uM
[2-(pyridin-3-ylmethylamino)pyrimidin-5-yl]-thiophen-2-ylmethanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	0.1600	uM
(2R)-N-[4-(3-fluorophenyl)-3-oxobutyl]-2,4-dihydroxy-3,3-dimethylbutanamide	1892118: Inhibition of human serum vanin-1 using pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 10 mins followed by substrate addition by fluorometry	ic50	0.1600	uM
N-[(3S)-1-[6-[(4-hydroxy-2-methylbutan-2-yl)amino]pyridine-3-carbonyl]pyrrolidin-3-yl]-N-methylacetamide	1724647: Inhibition of vanin-1 (unknown origin)	ic50	0.2000	uM
N-methyl-N-[(3S)-1-[6-(2-methylbutan-2-ylamino)pyridine-3-carbonyl]pyrrolidin-3-yl]acetamide	1724647: Inhibition of vanin-1 (unknown origin)	ic50	0.2000	uM
N-[(3S)-1-[6-(tert-butylamino)pyridine-3-carbonyl]pyrrolidin-3-yl]-3,3-difluoro-N-methylcyclobutane-1-carboxamide	1724647: Inhibition of vanin-1 (unknown origin)	ic50	0.2000	uM
(2R)-N-[4-(2-fluorophenyl)-3-oxobutyl]-2,4-dihydroxy-3,3-dimethylbutanamide	1892118: Inhibition of human serum vanin-1 using pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 10 mins followed by substrate addition by fluorometry	ic50	0.2300	uM
[6-(tert-butylamino)-3-pyridinyl]-(3-methyl-3-pyridin-2-ylazetidin-1-yl)methanone	1724647: Inhibition of vanin-1 (unknown origin)	ic50	0.3000	uM
(2S)-N-[(3S)-1-[6-(tert-butylamino)pyridine-3-carbonyl]pyrrolidin-3-yl]-N-methyloxolane-2-carboxamide	1724647: Inhibition of vanin-1 (unknown origin)	ic50	0.3000	uM
3-[(3S)-1-[6-(tert-butylamino)pyridine-3-carbonyl]pyrrolidin-3-yl]-1,3-oxazolidin-2-one	1724647: Inhibition of vanin-1 (unknown origin)	ic50	0.3000	uM
(2R)-2,4-dihydroxy-3,3-dimethyl-N-[3-oxo-4-[3-(trifluoromethoxy)phenyl]butyl]butanamide	1892118: Inhibition of human serum vanin-1 using pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 10 mins followed by substrate addition by fluorometry	ic50	0.4100	uM
(2R)-N-[4-(3,4-dichlorophenyl)-3-oxobutyl]-2,4-dihydroxy-3,3-dimethylbutanamide	1892118: Inhibition of human serum vanin-1 using pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 10 mins followed by substrate addition by fluorometry	ic50	0.6000	uM
(2R)-N-[4-(4-chlorophenyl)-3-oxobutyl]-2,4-dihydroxy-3,3-dimethylbutanamide	1892118: Inhibition of human serum vanin-1 using pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 10 mins followed by substrate addition by fluorometry	ic50	0.7700	uM
(2R)-2,4-dihydroxy-N-[4-(4-methoxyphenyl)-3-oxobutyl]-3,3-dimethylbutanamide	1892118: Inhibition of human serum vanin-1 using pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 10 mins followed by substrate addition by fluorometry	ic50	0.7700	uM
(2R)-2,4-dihydroxy-3,3-dimethyl-N-(3-oxo-4-phenylbutyl)butanamide	1892118: Inhibition of human serum vanin-1 using pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 10 mins followed by substrate addition by fluorometry	ic50	0.7800	uM
[(3S)-3-methylsulfonylpiperidin-1-yl]-[2-[(1-pyrimidin-5-ylcyclopropyl)amino]pyrimidin-5-yl]methanone	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	1.1000	uM
(3S)-1-[2-[(1-pyrimidin-5-ylcyclopropyl)amino]pyrimidine-5-carbonyl]piperidine-3-carbonitrile	1824860: Inhibition of recombinant N-terminal FLAG/His6-tagged human vanin-1 expressed in CHO cells using Pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins	ic50	1.2000	uM
(2R)-2,4-dihydroxy-3,3-dimethyl-N-[4-(4-methylphenyl)-3-oxobutyl]butanamide	1892118: Inhibition of human serum vanin-1 using pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 10 mins followed by substrate addition by fluorometry	ic50	1.2400	uM
(2R)-2,4-dihydroxy-3,3-dimethyl-N-(4-naphthalen-2-yl-3-oxobutyl)butanamide	1892118: Inhibition of human serum vanin-1 using pantetheine-7-amino-4-trifluoromethykournarin as substrate preincubated for 10 mins followed by substrate addition by fluorometry	ic50	2.8400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	4
Acetaminophen	affects cotreatment, decreases expression	3
Cyclosporine	decreases expression, increases expression	3
Estradiol	affects cotreatment, increases expression, decreases expression	2
Formaldehyde	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Asian ginseng	affects cotreatment, decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
fenofibric acid	affects binding, increases expression	1
allyl alcohol	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
citreoviridin	decreases expression	1
butyraldehyde	increases expression	1
ciglitazone	affects binding, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	increases expression	1
NSC 689534	increases expression	1
Rosiglitazone	increases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	decreases expression	1
Troglitazone	increases expression	1
Bosentan	affects expression	1
Leflunomide	increases expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Amphotericin B	decreases expression	1
Vehicle Emissions	increases abundance, increases expression, increases reaction	1
Azathioprine	increases expression	1

ChEMBL screening assays

20 unique, capped per target: 20 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4730318	Binding	Inhibition of vanin-1 (unknown origin)	Novel Heteroaromatic Compounds as Vanin Inhibitors. — ACS Med Chem Lett

Clinical trials (associated diseases)

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