Top ▲

vanin 1

Click here for help

Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 3063

Nomenclature: vanin 1

Family: Hydrolases & Lipases

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 513 6q23.2 VNN1 vanin 1 7
Mouse - 512 10 A4 Vnn1 vanin 1
Rat - 512 Vnn1 vanin 1
Previous and Unofficial Names Click here for help
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Enzyme Reaction Click here for help
EC Number:
Description Reaction Reference
Hydrolysis of pantothenic acid (vitamin B5) to release cysteamine (R)-pantetheine + H(2)O <=> (R)-pantothenate + 2-aminoethanethiol

Download all structure-activity data for this target as a CSV file go icon to follow link

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
example 25 [WO2018228934] Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 10.0 pIC50 5
pIC50 10.0 (IC50 1x10-10 M) [5]
Description: Measuring inhibition of pantothenic acid formation by test compound, as detected by RapidFire mass spectrometry.
vanin-1 inhibitor [PMID: 33196323] Small molecule or natural product Immunopharmacology Ligand Mm Inhibition 8.8 pIC50 14
pIC50 8.8 (IC50 1.5x10-9 M) [14]
vanin-1 inhibitor [PMID: 33196323] Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 8.5 pIC50 14
pIC50 8.5 (IC50 3.4x10-9 M) [14]
View species-specific inhibitor tables
Immunopharmacology Comments
Mounting evidence indicates that vanin 1 is involved in inflammation associated with diseases including systemic lupus erythematosus [13], systemic sclerosis [10] and colitis [3,9,12]. In murine models increased vanin 1 activity in the gut epithelium has been implicated in promoting tissue damage and inflammation by reducing resistance to oxidative stress [2-3,11-12]. Elevated vanin 1 expression has been detected in intestinal epithelium in tissue biopsies from ulcerative colitis and Crohn's disease patients and a gain-of-function polymorphism in VNN1 is associated with increased susceptibility to irritable bowel syndrome [8]. Based on this (and other) evidence pharmacological inhibition of vanin 1 is being explored as a novel mechanism for the treatment of inflammatory diseases [5-6].
Immuno Process Associations
Immuno Process:  Cellular signalling
Immuno Process:  Chemotaxis & migration
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  Inflammation
Immuno Process:  T cell (activation)
Tissue Distribution Click here for help
Expressed in spleen, thymus, peripheral blood lymphocytes and small intestine
Species:  Human
Technique:  Northern blot
References:  7
Thymic perivascular cells (pericytes)
Species:  Mouse
References:  1
Physiological Consequences of Altering Gene Expression Click here for help
Vanin-1 null mice exhibit a glutathione-mediated tissue resistance to oxidative stress.
Species:  Mouse
References:  2
Gene Expression and Pathophysiology Comments
Vanin-1 expression is significantly increased in the colonic mucosa from IBD patients [8].
Biologically Significant Variants Click here for help
Type:  Naturally occurring SNPs
Species:  Human
Description:  Three SNPs in hVNN1 are statistically associated to IBD.
References:  8
General Comments
Vanin 1 is a GPI-anchored enzyme that involved in leukocyte homing to the thymus [1] and links metabolic disease to inflammation [4,15]. Vanin 1-catalysed production of cysteamine has been linked to increased oxidative stress in tissues resulting from decreased glutathione levels. In murine models increased vanin 1 activity in the gut epithelium has been implicated in promoting tissue damage and inflammation by reducing resistance to oxidative stress [2-3,11-12].


Show »

1. Aurrand-Lions M, Galland F, Bazin H, Zakharyev VM, Imhof BA, Naquet P. (1996) Vanin-1, a novel GPI-linked perivascular molecule involved in thymus homing. Immunity, 5 (5): 391-405. [PMID:8934567]

2. Berruyer C, Martin FM, Castellano R, Macone A, Malergue F, Garrido-Urbani S, Millet V, Imbert J, Duprè S, Pitari G et al.. (2004) Vanin-1-/- mice exhibit a glutathione-mediated tissue resistance to oxidative stress. Mol Cell Biol, 24 (16): 7214-24. [PMID:15282320]

3. Berruyer C, Pouyet L, Millet V, Martin FM, LeGoffic A, Canonici A, Garcia S, Bagnis C, Naquet P, Galland F. (2006) Vanin-1 licenses inflammatory mediator production by gut epithelial cells and controls colitis by antagonizing peroxisome proliferator-activated receptor gamma activity. J Exp Med, 203 (13): 2817-27. [PMID:17145956]

4. Boersma YL, Newman J, Adams TE, Cowieson N, Krippner G, Bozaoglu K, Peat TS. (2014) The structure of vanin 1: a key enzyme linking metabolic disease and inflammation. Acta Crystallogr D Biol Crystallogr, 70 (Pt 12): 3320-9. [PMID:25478849]

5. Bosanac T, Burke MJ, Cook BN, DiSalvo DT, Kirrane Jr TM, Shen Y. (2018) HETEROAROMATIC COMPOUNDS AS VANIN INHIBITORS. Patent number: WO2018228934. Assignee: BOEHRINGER INGELHEIM INTERNATIONAL GMBH. Priority date: 12/06/2017. Publication date: 20/12/2018.

6. Casimiro-Garcia A, Condon JS, Flick AC, Gopalsamy A, Kirincich SJ, Mathias JP, Strobach JW, Xiang JS, Xing LH, Wang X. (2018) Novel heterocyclic compounds as inhibitors of vanin-1 enzyme. Patent number: US20180148420A1. Assignee: Pfizer Inc. Priority date: 29/05/2015. Publication date: 31/05/2018.

7. Galland F, Malergue F, Bazin H, Mattei MG, Aurrand-Lions M, Theillet C, Naquet P. (1998) Two human genes related to murine vanin-1 are located on the long arm of human chromosome 6. Genomics, 53 (2): 203-13. [PMID:9790769]

8. Gensollen T, Bourges C, Rihet P, Rostan A, Millet V, Noguchi T, Bourdon V, Sobol H, Dubuquoy L, Bertin B et al.. (2013) Functional polymorphisms in the regulatory regions of the VNN1 gene are associated with susceptibility to inflammatory bowel diseases. Inflamm Bowel Dis, 19 (11): 2315-25. [PMID:23949622]

9. Hosohata K, Ando H, Fujimura A. (2014) Early detection of renal injury using urinary vanin-1 in rats with experimental colitis. J Appl Toxicol, 34 (2): 184-90. [PMID:23307618]

10. Kavian N, Mehlal S, Marut W, Servettaz A, Giessner C, Bourges C, Nicco C, Chéreau C, Lemaréchal H, Dutilh MF et al.. (2016) Imbalance of the Vanin-1 Pathway in Systemic Sclerosis. J Immunol, 197 (8): 3326-3335. [PMID:27647831]

11. Naquet P, Pitari G, Duprè S, Galland F. (2014) Role of the Vnn1 pantetheinase in tissue tolerance to stress. Biochem Soc Trans, 42 (4): 1094-100. [PMID:25110008]

12. Pouyet L, Roisin-Bouffay C, Clément A, Millet V, Garcia S, Chasson L, Issaly N, Rostan A, Hofman P, Naquet P et al.. (2010) Epithelial vanin-1 controls inflammation-driven carcinogenesis in the colitis-associated colon cancer model. Inflamm Bowel Dis, 16 (1): 96-104. [PMID:19572375]

13. Sánchez-Muñoz F, Amezcua-Guerra LM, Macías-Palacios M, Márquez-Velasco R, Bojalil R. (2013) Vanin-1 as a potential novel biomarker for active nephritis in systemic lupus erythematosus. Lupus, 22 (3): 333-5. [PMID:23390193]

14. Unterschemmann K, Ehrmann A, Herzig I, Andreevski AL, Lustig K, Schmeck C, Eitner F, Grundmann M. (2021) Pharmacological inhibition of Vanin-1 is not protective in models of acute and chronic kidney disease. Am J Physiol Renal Physiol, 320 (1): F61-F73. [PMID:33196323]

15. van Diepen JA, Jansen PA, Ballak DB, Hijmans A, Rutjes FP, Tack CJ, Netea MG, Schalkwijk J, Stienstra R. (2016) Genetic and pharmacological inhibition of vanin-1 activity in animal models of type 2 diabetes. Sci Rep, 6: 21906. [PMID:26932716]

How to cite this page