ALPI

Summary

ALPI (alkaline phosphatase, intestinal, HGNC:437) is a protein-coding gene on chromosome 2q37.1, encoding Intestinal-type alkaline phosphatase (P09923). Alkaline phosphatase that can hydrolyze various phosphate compounds.

There are at least four distinct but related alkaline phosphatases: intestinal, placental, placental-like, and liver/bone/kidney (tissue non-specific). The intestinal alkaline phosphatase gene encodes a digestive brush-border enzyme. This enzyme is a component of the gut mucosal defense system and is thought to function in the detoxification of lipopolysaccharide, and in the prevention of bacterial translocation in the gut.

Source: NCBI Gene 248 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inflammatory bowel disease (Moderate, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 123 total — 1 likely-pathogenic
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001631

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:437
Approved symbol	ALPI
Name	alkaline phosphatase, intestinal
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Aliases	IAP
Ensembl gene	ENSG00000163295
Ensembl biotype	protein_coding
OMIM	171740
Entrez	248

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 nonsense_mediated_decay

ENST00000295463, ENST00000457560

RefSeq mRNA: 1 — MANE Select: NM_001631 NM_001631

CCDS: CCDS2492

Canonical transcript exons

ENST00000295463 — 11 exons

Exon	Start	End
ENSE00001073088	232456349	232456465
ENSE00001073090	232456153	232456266
ENSE00001145790	232458860	232460753
ENSE00003474912	232456580	232456695
ENSE00003480239	232457998	232458132
ENSE00003483714	232456899	232457073
ENSE00003486558	232458217	232458408
ENSE00003527884	232457565	232457699
ENSE00003558780	232457795	232457867
ENSE00003584240	232458632	232458748
ENSE00003648365	232457150	232457322

Expression profiles

Bgee: expression breadth broad, 41 present calls, max score 99.17.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.7352 / max 1670.0332, expressed in 44 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25970	2.6030	31
25969	1.1123	39
25971	0.0199	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.17	gold quality
duodenum	UBERON:0002114	95.89	gold quality
ileal mucosa	UBERON:0000331	93.41	gold quality
ileum	UBERON:0002116	93.34	silver quality
small intestine	UBERON:0002108	83.64	gold quality
small intestine Peyer’s patch	UBERON:0003454	82.72	gold quality
endometrium epithelium	UBERON:0004811	78.23	gold quality
mucosa of transverse colon	UBERON:0004991	77.52	gold quality
jejunum	UBERON:0002115	76.20	gold quality
tendon of biceps brachii	UBERON:0008188	75.76	gold quality
paraflocculus	UBERON:0005351	72.06	gold quality
rectum	UBERON:0001052	72.03	gold quality
frontal pole	UBERON:0002795	71.87	gold quality
middle frontal gyrus	UBERON:0002702	71.24	gold quality
olfactory bulb	UBERON:0002264	70.01	gold quality
parotid gland	UBERON:0001831	68.54	gold quality
buccal mucosa cell	CL:0002336	67.93	gold quality
Brodmann (1909) area 10	UBERON:0013541	65.84	gold quality
colonic mucosa	UBERON:0000317	64.99	gold quality
transverse colon	UBERON:0001157	63.80	gold quality
cerebellar vermis	UBERON:0004720	63.13	gold quality
secondary oocyte	CL:0000655	62.82	gold quality
oocyte	CL:0000023	62.27	gold quality
mucosa of sigmoid colon	UBERON:0004993	62.27	gold quality
quadriceps femoris	UBERON:0001377	61.18	gold quality
intestine	UBERON:0000160	61.09	gold quality
vastus lateralis	UBERON:0001379	61.02	gold quality
triceps brachii	UBERON:0001509	60.76	gold quality
gluteal muscle	UBERON:0002000	60.18	gold quality
gingival epithelium	UBERON:0001949	59.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX1, CDX2, FOXO1, GATA4, HNF4A, KLF4, SMAD2, SMAD3, SMAD4

miRNA regulators (miRDB)

74 targeting ALPI, 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-4455	100.00	65.48	1587
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6756-5P	99.82	67.97	2466
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
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306

Literature-anchored findings (GeneRIF, showing 29)

• the structural differences in human AP isoforms are demonstrated through models (PMID:12372831)
• intestinal alkaline transactivation by Kruppel-like factor-4 is likely mediated through a critical region located within the proximal IAP promoter region (PMID:12919939)
• Northern blotting detected expression of two IAP transcripts, which were increased approximately 3-fold in response to thyroid hormone (PMID:15143152)
• receptor for Aeromonas sobria hemolysin (PMID:15715171)
• Cdx1 activates the IAP gene via a novel cis element, whereas Cdx2 inhibits the Cdx1 effects (PMID:15774940)
• Cotransfection with an HNF-4alpha expression vector demonstrated a direct activation of the ALPI promoter through -94 to -82 element (PMID:15831710)
• Crohn’s disease increases the alkaline phosphatase activity in the intestine. Use histochemistry to differentiate Crohn’s disease/ulcerative colitis. (PMID:17498884)
• has the ability to detoxify lipopolysaccharide and prevent bacterial invasion across the gut mucosal barrier. IAP expression and function are lost with starvation and maintained by enteral feeding (PMID:18292227)
• Cathepsin C propeptide interacts with intestinal alkaline phosphatase (IAP) and heat shock cognate protein 70. The propeptide of cathepsin C may stimulate the sorting to the lysosome contributing to the degradation of IAP in Caco-2 cells. (PMID:18307834)
• Suggest role for lysophosphatidylcholine in brush-border intestinal alkaline phosphatase release and restoration. (PMID:19407215)
• Mechanism of IAP action appears to be through dephosphorylation of specific bacterial components, including LPS, CpG DNA, and flagellin, and not on live bacteria. IAP likely targets these bacterially derived molecules as gut mucosal defense factor. (PMID:20489044)
• we are the first to demonstrate the alteration of protein expression of iAP in the duodenal mucosa of children with newly diagnosed coeliac disease (PMID:22262031)
• Report lowered intestinal alkaline phosphatase in the colonic mucosa of children with inflammatory bowel disease. (PMID:22783049)
• Data indicate that histone deacetylase inhibitors (HDACi) induce intestinal alkaline phosphatase (ALPi) in a subset of colon cancer cell lines in a Kruppel-like factor 5 (KLF5)-dependent manner. (PMID:25037223)
• The expression of ALPi and MUC5AC in cocultures of Caco-2 and HT29 cells developed for permeability studies is reported. (PMID:26299896)
• A High Level of Intestinal Alkaline Phosphatase Is Protective Against Type 2 Diabetes Mellitus Irrespective of Obesity (PMID:26844282)
• Review of the role of intestinal alkaline phosphatase in inflammatory diseases. Loss of IAP expression or function is associated with increased intestinal inflammation, dysbiosis, bacterial translocation and subsequently systemic inflammation. (PMID:27083970)
• Intestinal alkaline phosphatase is a major regulator of gut mucosal permeability and appears to work at least partly through improving tight junction protein levels and localization. (PMID:27106638)
• Data indicate alkaline phosphatase (AP) as the primary soluble ectonucleotidase in infants undergoing cardiopulmonary bypass and show decreased capacity to clear AMP when AP activity decreases post-bypass. (PMID:27384524)
• Expressions of human intestinal alkaline phosphatase and sucrase-isomaltase, which are intestinal differentiation markers, were highly enhanced in Caco-2 cells by menaquinone-4. (PMID:27865621)
• Data confirm that, in enterocytes (Caco-2 cells), 1-alpha,25-dihydroxy-vitamin-D3 up-regulates expression of 2 isoforms of IAP, alternative splicing variants. (PMID:28931466)
• Study establishes that IAP deficiency in stool is associated with ischemic heart disease (IHD), and a high level of IAP might play a protective role against IHD. (PMID:31915470)
• A role for intestinal alkaline phosphatase in preventing liver fibrosis. (PMID:33391458)
• Role of Intestinal Alkaline Phosphatase in Innate Immunity. (PMID:34944428)
• Intestinal alkaline phosphatase deficiency increases the risk of diabetes. (PMID:35082135)
• Intestinal Alkaline Phosphatase Prevents Sulfate Reducing Bacteria-Induced Increased Tight Junction Permeability by Inhibiting Snail Pathway. (PMID:35694541)
• Characterization and Structure of Alternatively Spliced Transcript Variant of Human Intestinal Alkaline Phosphatase (ALPI) Gene. (PMID:36047100)
• The role of intestinal alkaline phosphatase in the development of necrotizing enterocolitis. (PMID:37300991)
• Effect of Surgery on Postoperative Levels of the Gut Homeostasis-Regulating Enzyme Intestinal Alkaline Phosphatase. (PMID:37870235)

Cross-species orthologs

21 orthologs

Organism	Symbol	Gene ID
danio_rerio	alpi.2	ENSDARG00000053774
mus_musculus	Alppl2	ENSMUSG00000026246
mus_musculus	Akp3	ENSMUSG00000036500
mus_musculus	Alpi	ENSMUSG00000079440
rattus_norvegicus	Alpi	ENSRNOG00000030020
rattus_norvegicus	Alpp	ENSRNOG00000033672
rattus_norvegicus	Alpg	ENSRNOG00000042889
rattus_norvegicus	Akp3	ENSRNOG00000058652
drosophila_melanogaster	Alp4	FBGN0016123
drosophila_melanogaster	Alp11	FBGN0030661
drosophila_melanogaster	Alp12	FBGN0032779
drosophila_melanogaster	Alp6	FBGN0033423
drosophila_melanogaster	Alp7	FBGN0034710
drosophila_melanogaster	Alp8	FBGN0034712
drosophila_melanogaster	Alp10	FBGN0035619
drosophila_melanogaster	Alp9	FBGN0035620
drosophila_melanogaster	Alp13	FBGN0037786
drosophila_melanogaster	Alp5	FBGN0038845
drosophila_melanogaster	phu	FBGN0043791
drosophila_melanogaster	Alp1	FBGN0283479
drosophila_melanogaster	Alp2	FBGN0283480

Paralogs (3): ALPL (ENSG00000162551), ALPP (ENSG00000163283), ALPG (ENSG00000163286)

Protein

Protein identifiers

Intestinal-type alkaline phosphatase — P09923 (reviewed: P09923)

All UniProt accessions (2): P09923, F8WEQ0

UniProt curated annotations — full annotation on UniProt →

Function. Alkaline phosphatase that can hydrolyze various phosphate compounds.

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane.

Cofactor. Binds 1 Mg(2+) ion. Binds 2 Zn(2+) ions.

Miscellaneous. In most mammals there are four different isozymes: placental (ALPP), germ cell (ALPG), intestinal (ALPI) and tissue non-specific (liver/bone/kidney) (ALPL/TNAP).

Similarity. Belongs to the alkaline phosphatase family.

RefSeq proteins (1): NP_001622* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001952	Alkaline_phosphatase	Family
IPR017850	Alkaline_phosphatase_core_sf	Homologous_superfamily
IPR018299	Alkaline_phosphatase_AS	Active_site

Pfam: PF00245

Catalyzed reactions (Rhea), 1 shown:

• a phosphate monoester + H2O = an alcohol + phosphate (RHEA:15017)

UniProt features (29 total): binding site 14, glycosylation site 3, sequence conflict 3, disulfide bond 2, sequence variant 2, signal peptide 1, chain 1, lipid moiety-binding region 1, propeptide 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09923-F1	93.46	0.90

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 (1): 111 (phosphoserine intermediate)

Ligand- & substrate-binding residues (14): 289; 304; 330; 335; 339; 376; 377; 451; 61; 61; 111; 174 …

Post-translational modifications (1): 503

Disulfide bonds (2): 140–202, 486–493

Glycosylation sites (3): 141, 268, 429

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1483166	Synthesis of PA
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins
R-HSA-8935690	Digestion

MSigDB gene sets: 75 (showing top): GCM_PRKCG, PPAR_DR1_Q2, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_DEPHOSPHORYLATION, SABATES_COLORECTAL_ADENOMA_DN, GOCC_SIDE_OF_MEMBRANE, GOMF_MAGNESIUM_ION_BINDING, ER_Q6_02, GOMF_PROTEASE_BINDING, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_PHOSPHORIC_ESTER_HYDROLASE_ACTIVITY, COUP_DR1_Q6, YOSHIMURA_MAPK8_TARGETS_UP, MODULE_7, MIKKELSEN_MCV6_ICP_WITH_H3K27ME3

GO Biological Process (1): dephosphorylation (GO:0016311)

GO Molecular Function (8): magnesium ion binding (GO:0000287), protease binding (GO:0002020), alkaline phosphatase activity (GO:0004035), zinc ion binding (GO:0008270), protein binding (GO:0005515), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791), metal ion binding (GO:0046872)

GO Cellular Component (4): extracellular region (GO:0005576), plasma membrane (GO:0005886), side of membrane (GO:0098552), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1
Post-translational protein modification	1
Digestion and absorption	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
membrane	2
phosphate-containing compound metabolic process	1
metal ion binding	1
enzyme binding	1
phosphatase activity	1
transition metal ion binding	1
binding	1
catalytic activity	1
phosphoric ester hydrolase activity	1
cation binding	1
cell periphery	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

1428 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALPI	CHRND	Q07001	780
ALPI	INHA	P05111	778
ALPI	COL4A3	Q01955	695
ALPI	GGT6	Q6P531	670
ALPI	PAX3	P23760	669
ALPI	GOT1L1	Q8NHS2	660
ALPI	GGT7	Q9UJ14	657
ALPI	GGT2P	P36268	612
ALPI	GGT5	P36269	591
ALPI	GOT1	P17174	576
ALPI	PAX7	P23759	546
ALPI	GGT1	P19440	541
ALPI	GOT2	P00505	519
ALPI	LDHAL6B	Q9BYZ2	514
ALPI	LDHAL6A	Q6ZMR3	512

IntAct

36 interactions, top by confidence:

A	B	Type	Score
ALPI	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.670
NOTCH2NLA	ALPI	psi-mi:“MI:0915”(physical association)	0.670
ALPI		psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	ALPI	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	ALPI	psi-mi:“MI:0915”(physical association)	0.560
	ALPI	psi-mi:“MI:0915”(physical association)	0.560
ALPI	ALPP	psi-mi:“MI:0914”(association)	0.530
ALPG	ALPP	psi-mi:“MI:0914”(association)	0.530
ALPI	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
Actb		psi-mi:“MI:0914”(association)	0.350
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
METTL14	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
SCARB2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
VMP1	TPM3	psi-mi:“MI:0914”(association)	0.350
MOSPD2	FLNA	psi-mi:“MI:0914”(association)	0.350
ALPG	POTEF	psi-mi:“MI:0914”(association)	0.350
ALPI	RTCA	psi-mi:“MI:0914”(association)	0.350

BioGRID (84): KRTAP10-9 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), ALPI (Two-hybrid), ALPI (Affinity Capture-MS), ALPI (Affinity Capture-MS), ALPP (Affinity Capture-MS), ARL2 (Affinity Capture-MS), TUBB1 (Affinity Capture-MS), ARF5 (Affinity Capture-MS), DDX19B (Affinity Capture-MS), RAB39B (Affinity Capture-MS), RDH13 (Affinity Capture-MS), ARL8B (Affinity Capture-MS)

ESM2 similar proteins: A0A2I4HXH5, B6EWW8, F8S0Z7, O35409, O77564, P04062, P04068, P05106, P05186, P05187, P07099, P08289, P09242, P09487, P09923, P10696, P15693, P17439, P19111, P21588, P21589, P24822, P24823, P28492, P51740, P58242, P70627, P83456, Q04609, Q05927, Q13822, Q17QK3, Q29486, Q2KHZ8, Q3TIW9, Q571F8, Q5EZ72, Q5R8E3, Q5RDN7, Q61503

Diamond homologs: O60109, P00634, P05186, P05187, P08289, P09242, P09487, P09923, P10696, P11491, P15693, P19111, P21948, P24822, P24823, P29523, P51740, P83456, Q24238, Q29486, Q92058, P19405, P19147, P35483, Q02QC9, P09401, P19406

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	89
Likely benign	21
Benign	11

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1335447	NM_001631.5(ALPI):c.1315C>T (p.Gln439Ter)	Likely pathogenic

SpliceAI

952 predictions. Top by Δscore:

Variant	Effect	Δscore
2:232456342:T:TA	acceptor_gain	1.0000
2:232456343:G:A	acceptor_gain	1.0000
2:232456347:A:AG	acceptor_gain	1.0000
2:232456348:G:GA	acceptor_gain	1.0000
2:232456348:GCT:G	acceptor_gain	1.0000
2:232456348:GCTGA:G	acceptor_gain	1.0000
2:232456462:GATG:G	donor_gain	1.0000
2:232456463:ATGG:A	donor_loss	1.0000
2:232456464:TG:T	donor_gain	1.0000
2:232456465:GG:G	donor_gain	1.0000
2:232456466:GTGA:G	donor_gain	1.0000
2:232456468:GA:G	donor_gain	1.0000
2:232456470:G:GG	donor_gain	1.0000
2:232456575:TTCAG:T	acceptor_loss	1.0000
2:232456576:TCAG:T	acceptor_loss	1.0000
2:232456577:CAGG:C	acceptor_loss	1.0000
2:232456578:A:AG	acceptor_gain	1.0000
2:232456579:G:GG	acceptor_gain	1.0000
2:232456579:GGGTT:G	acceptor_gain	1.0000
2:232456693:AAGGT:A	donor_loss	1.0000
2:232456695:GGTAA:G	donor_loss	1.0000
2:232456696:G:GA	donor_loss	1.0000
2:232456697:T:A	donor_loss	1.0000
2:232456894:CGCA:C	acceptor_loss	1.0000
2:232456896:CAGA:C	acceptor_loss	1.0000
2:232456897:A:AG	acceptor_gain	1.0000
2:232456898:G:GA	acceptor_gain	1.0000
2:232456898:GAC:G	acceptor_gain	1.0000
2:232456898:GACA:G	acceptor_gain	1.0000
2:232456898:GACAT:G	acceptor_gain	1.0000

AlphaMissense

3423 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:232458229:A:T	D335V	0.998
2:232456929:A:C	S111R	0.996
2:232456931:C:A	S111R	0.996
2:232456931:C:G	S111R	0.996
2:232458229:A:C	D335A	0.996
2:232458230:C:A	D335E	0.996
2:232458230:C:G	D335E	0.996
2:232458922:G:C	D455H	0.996
2:232456465:G:T	G62W	0.995
2:232456463:A:T	D61V	0.994
2:232458352:A:T	D376V	0.994
2:232456610:G:T	R72M	0.993
2:232458228:G:C	D335H	0.993
2:232458240:C:G	H339D	0.993
2:232456604:C:A	A70D	0.992
2:232456967:G:C	K123N	0.992
2:232456967:G:T	K123N	0.992
2:232458223:G:C	R333P	0.992
2:232458356:C:A	H377Q	0.992
2:232458356:C:G	H377Q	0.992
2:232458360:C:G	H379D	0.992
2:232458114:T:C	F325L	0.991
2:232458116:C:A	F325L	0.991
2:232458116:C:G	F325L	0.991
2:232458229:A:G	D335G	0.991
2:232458241:A:C	H339P	0.991
2:232458265:T:C	L347P	0.991
2:232458349:C:A	A375D	0.991
2:232458351:G:C	D376H	0.991
2:232458353:C:A	D376E	0.991

dbSNP variants (sampled 300 via entrez): RS1000641323 (2:232460134 A>G), RS1000844879 (2:232457372 C>T), RS1001975867 (2:232455605 C>T), RS1002881305 (2:232460453 A>C), RS1003171992 (2:232454159 G>A), RS1004196955 (2:232457256 T>A), RS1004662106 (2:232457482 G>A), RS1005252356 (2:232454643 A>G), RS1005259093 (2:232458683 A>G), RS1005312451 (2:232459185 G>A), RS1005350424 (2:232458910 C>T), RS1005404443 (2:232459463 A>C,T), RS1005590311 (2:232454801 C>A,T), RS1006206819 (2:232459582 C>T), RS1006368349 (2:232454649 C>G)

Disease associations

OMIM: gene MIM:171740 | disease phenotypes: MIM:266600, MIM:253290

GenCC curated gene-disease

Disease	Classification	Inheritance
inflammatory bowel disease	Moderate	Autosomal recessive

Mondo (2): inflammatory bowel disease (MONDO:0005265), lethal multiple pterygium syndrome (MONDO:0009668)

Orphanet (2): Rare inflammatory bowel disease (Orphanet:104012), Lethal multiple pterygium syndrome (Orphanet:33108)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003944_12	Hepcidin/ferritin ratio	7.000000e-07
GCST003944_13	Hepcidin/ferritin ratio	2.000000e-06
GCST010002_411	Refractive error	1.000000e-123

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007901	hepcidin:ferritin ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D015212	Inflammatory Bowel Diseases	C06.405.205.731; C06.405.469.432

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5573 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 686,790 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1454	LEVAMISOLE	4	56,423
CHEMBL140	CURCUMIN	3	93,882
CHEMBL301523	PHENYLALANINE	3	530,828
CHEMBL250450	ISOQUERCETIN	2	1,626
CHEMBL442687	TIOXOLONE	2	4,031

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

Binding affinities (BindingDB)

230 measured of 406 human assays (454 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-chloranyl-N-(3,4-dihydro-2H-thiochromen-4-yl)-3-sulfamoyl-benzamide	IC50	121 nM
(2-anilinopyrimidin-4-yl)-phenyl-amine	IC50	423 nM	US-9249124: Aurora kinase inhibitors and methods of making and using thereof
6-(2-fluorophenyl)-2-[4-(2-hydroxyethyl)-3-methyl-5-oxo-2,5-dihydro-1H-pyrazol-1-yl]-4(3H)-pyrimidinone	IC50	1070 nM
2-[2-oxidanylidene-2-[2-[(Z)-(3-oxidanyl-4-oxidanylidene-cyclohexa-2,5-dien-1-ylidene)methyl]hydrazinyl]ethoxy]-N’’-[(Z)-(3-oxidanyl-4-oxidanylidene-cyclohexa-2,5-dien-1-ylidene)methyl]benzohydrazide	IC50	1070 nM
2-[5-[(Z)-(3-bromanyl-8-oxidanylidene-[1,3]thiazolo[4,5]imidazo[1,2-b]pyridin-7-ylidene)methyl]furan-2-yl]benzoic acid	IC50	1250 nM
Cephalochromin	IC50	1490 nM
2-[[5-(1,3-benzothiazol-2-ylsulfanylmethyl)-4-ethyl-1,2,4-triazol-3-yl]sulfanyl]-1-(3,4-dihydroxyphenyl)ethanone	IC50	1520 nM
(5Z)-3-[[(E)-(6-keto-3-nitro-cyclohexa-2,4-dien-1-ylidene)methyl]amino]-5-[(5-methyl-2-furyl)methylene]-2-thioxo-thiazolidin-4-one	IC50	1530 nM
(2Z)-2-(3,4-dihydroxybenzylidene)-6-hydroxy-coumaran-3-one	IC50	1530 nM
3-[6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-5-phenyl-pentanoic acid	IC50	1610 nM
(5Z)-5-[(E)-3-(2-furanyl)prop-2-enylidene]-3-(4-hydroxyphenyl)-2-sulfanylidene-4-thiazolidinone	IC50	1720 nM
4-[5-[(Z)-[3-(1,1-diketothiolan-3-yl)-4-keto-2-thioxo-thiazolidin-5-ylidene]methyl]-2-furyl]benzenesulfonamide	IC50	1850 nM
MLS000102658	EC50	1910 nM
3-(4-methoxyphenyl)-6-methyl-2H-1,4-benzoxazine	EC50	1950 nM
4-(2-benzylsulfanylethyl)pyridine;phosphoric acid	IC50	2010 nM
2-[5-(2-furanyl)-1H-1,2,4-triazol-3-yl]-1,3-dioxo-5-isoindolecarboxylic acid	IC50	2060 nM
MLS001224314	IC50	2080 nM
SMR000369921	IC50	2350 nM
MLS000778637	IC50	2420 nM
MLS000550779	EC50	2670 nM
(1S)-1,5-anhydro-1-(1,3,6,7-tetrahydroxy-9-oxo-9H-xanthen-2-yl)-D-glucitol	IC50	2710 nM
5,6-Dimethyl-2-[1-(1-thiophen-2-ylmethyl-1H-tetrazol-5-ylmethyl)-piperidin-4-yl]-1H-benzoimidazole	IC50	2730 nM
MLS000720395	IC50	2820 nM
3-[5-(methylamino)-1,3,4-thiadiazol-2-yl]-1-benzopyran-2-one	IC50	2850 nM
2-(3,4-dihydroxyphenyl)-7,8-dihydroxy-2,3-dihydrochromen-4-one	IC50	2990 nM
2-amino-3-hydroxy-N’-(2,3,4-trihydroxybenzyl)propionohydrazide;hydrochloride	IC50	3050 nM
MLS000778639	IC50	3100 nM
5-amino-6-[(Z)-(3-hydroxy-4-keto-cyclohexa-2,5-dien-1-ylidene)methyl]-3-phenyl-thiazolo[3,2-a]pyrimidin-7-one	IC50	3100 nM
(+)-haematoxylin	IC50	3440 nM
2-[(2-keto-1H-benzo[cd]indol-6-yl)sulfonyl-methyl-amino]benzoic acid	IC50	3850 nM
(5E)-5-[(5-methyl-2-furanyl)methylidene]-4-sulfanylidene-2-thiazolidinone	IC50	4160 nM
1-(3,4-dihydroxyphenyl)-2-[[4-ethyl-5-(2-methoxyphenyl)-1,2,4-triazol-3-yl]sulfanyl]ethanone	IC50	4360 nM
3-[1-(3,4-Dihydroxy-phenyl)-meth-(E)-ylidene]-4-imino-7-methanesulfonyl-3,4-dihydro-9-thia-1,4a-diaza -fluoren-2-one	IC50	4570 nM
MLS000762704	IC50	5080 nM
1-(4-hydroxyphenyl)-3-oxidanyl-propan-1-one	IC50	5160 nM
N-[(5Z)-4-oxo-5-(2-oxo-1H-indol-3-ylidene)-2-sulfanylidene-3-thiazolidinyl]benzamide	IC50	5310 nM
9-bromanyl-4-oxidanyl-6H-chromeno[2,3-b]indol-3-one	IC50	5380 nM
SMR000496526	EC50	5730 nM
SMR000339621	IC50	5950 nM
3-(1,3-benzodioxol-5-yl)-N’-[(E)-(6-oxocyclohexa-2,4-dien-1-ylidene)methyl]-1H-pyrazole-5-carbohydrazide	EC50	6030 nM
(E)-3-(2-furanyl)-N-[(4-sulfamoylanilino)-sulfanylidenemethyl]-2-propenamide	IC50	6460 nM
4-Methyl-5-oxo-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2-hydroxy-3-methoxy-benzylidene)-hydrazide	EC50	6470 nM
SMR001522428	IC50	6580 nM
8,9-bis(oxidanyl)-[1]benzofuro[3,2-c]chromen-6-one	IC50	6690 nM
SMR000612865	IC50	6940 nM
4-Methyl-5-oxo-4,5-dihydro-1H-pyrazole-3-carboxylic acid (2,4-dihydroxy-benzylidene)-hydrazide	IC50	7720 nM
MLS001158749	IC50	7780 nM
4-oxidanylidene-N-(quinolin-7-ylmethylideneamino)-1H-quinazoline-2-carboxamide	EC50	7780 nM
(2E)-3-(3,4-dihydroxyphenyl)-2-[(3,4-dihydroxyphenyl)carbonyl]prop-2-enenitrile	EC50	8030 nM
5-(5-methylfuran-2-yl)-N’-[(E)-(6-oxidanylidenecyclohexa-2,4-dien-1-ylidene)methyl]-1H-pyrazole-3-carbohydrazide	EC50	8040 nM

ChEMBL bioactivities

159 potent at pChembl≥5 of 361 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.62	IC50	240	nM	CHEMBL4286917
6.58	IC50	262	nM	CHEMBL1329826
6.51	IC50	310	nM	CHEMBL4292485
6.44	IC50	360	nM	CHEMBL4292054
6.37	IC50	430	nM	CHEMBL4284174
6.36	IC50	440	nM	CHEMBL4283860
6.34	IC50	460	nM	CHEMBL4286723
6.32	IC50	480	nM	CHEMBL4291826
6.32	IC50	480	nM	CHEMBL4279537
6.25	IC50	565	nM	THUNBERGINOL B
6.17	IC50	680	nM	CHEMBL4294808
6.15	IC50	710	nM	CHEMBL4289799
6.15	IC50	710	nM	CHEMBL4281863
6.13	IC50	740	nM	CHEMBL4281616
6.12	IC50	760	nM	CHEMBL4277341
6.12	IC50	760	nM	CHEMBL4288407
6.10	IC50	790	nM	CHEMBL4292887
6.05	IC50	890	nM	CHEMBL4281930
6.05	IC50	891	nM	CHEMBL1506682
5.98	IC50	1040	nM	CHEMBL4283809
5.97	IC50	1070	nM	CHEMBL3144928
5.96	IC50	1110	nM	CHEMBL4069435
5.95	IC50	1120	nM	CHEMBL4287459
5.92	IC50	1210	nM	CHEMBL4289564
5.92	IC50	1190	nM	CHEMBL1329826
5.91	IC50	1240	nM	CHEMBL4294381
5.91	IC50	1230	nM	CHEMBL1420033
5.89	IC50	1290	nM	CHEMBL1529932
5.88	IC50	1330	nM	CHEMBL4105082
5.82	IC50	1530	nM	CHEMBL4290987
5.78	IC50	1670	nM	CHEMBL4284091
5.76	IC50	1750	nM	CHEMBL4281206
5.76	IC50	1740	nM	CHEMBL3198600
5.75	IC50	1780	nM	CHEMBL4287165
5.75	IC50	1760	nM	CHEMBL1529932
5.71	IC50	1970	nM	CHEMBL1578178
5.70	IC50	2020	nM	CHEMBL4295150
5.68	IC50	2100	nM	CHEMBL1733511
5.67	IC50	2130	nM	CHEMBL4103420
5.67	IC50	2120	nM	CHEMBL1549540
5.66	IC50	2170	nM	THUNBERGINOL B
5.65	IC50	2260	nM	CHEMBL4080152
5.65	IC50	2220	nM	CHEMBL4280737
5.63	IC50	2360	nM	CHEMBL3144972
5.59	IC50	2550	nM	CHEMBL4287568
5.57	IC50	2720	nM	CHEMBL4093867
5.57	IC50	2680	nM	CHEMBL56393
5.55	IC50	2810	nM	CHEMBL4090465
5.55	IC50	2820	nM	CHEMBL3144972
5.54	IC50	2870	nM	CHEMBL4075025

PubChem BioAssay actives

64 with measured affinity, of 124 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
2-[4-(trifluoromethoxy)phenyl]-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	0.2400	uM
2-(propylamino)-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	0.3100	uM
2-(4-methylphenyl)-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	0.3600	uM
2-phenyl-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	0.4300	uM
2-(3-methoxyanilino)-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	0.4400	uM
2-(3,5-dimethylphenyl)-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	0.4600	uM
2-(3-nitrophenyl)-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	0.4800	uM
2-(4-methoxyphenyl)-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	0.4800	uM
7-(trifluoromethyl)-2-[3-(trifluoromethyl)phenyl]-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	0.6800	uM
2-(butylamino)-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	0.7100	uM
2-(4-aminoanilino)-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	0.7100	uM
2-(3-fluorophenyl)-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	0.7400	uM
2-(pentylamino)-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	0.7600	uM
2-(3,5-dimethoxyphenyl)-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	0.7600	uM
2-(4-ethoxyphenyl)-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	0.7900	uM
2-(prop-2-enylamino)-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	0.8900	uM
(3Z)-3-[(3-methoxyphenyl)methylidene]-1,1-dioxo-1lambda6,2-benzothiazin-4-one	1422553: Inhibition of human IAP expressed in African green monkey COS7 cell membranes using CDP-star as substrate pretreated for 5 to 10 mins followed by substrate addition and measured after 15 to 20 mins by spectrophotometric method	ic50	1.0400	uM
(3-cyano-4-methyl-2-oxochromen-7-yl) 4-nitrobenzenesulfonate	1444566: Inhibition of human IAP using CDP-star as substrate pretreated for 10 mins followed by substrate addition measured after 10 mins by spectrophotometric method	ic50	1.1100	uM
3-[5-oxo-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-2-yl]benzonitrile	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	1.1200	uM
(3Z)-3-[(3-hydroxyphenyl)methylidene]-1,1-dioxo-1lambda6,2-benzothiazin-4-one	1422553: Inhibition of human IAP expressed in African green monkey COS7 cell membranes using CDP-star as substrate pretreated for 5 to 10 mins followed by substrate addition and measured after 15 to 20 mins by spectrophotometric method	ic50	1.2100	uM
(3Z)-3-[(2-methoxyphenyl)methylidene]-1,1-dioxo-1lambda6,2-benzothiazin-4-one	1422553: Inhibition of human IAP expressed in African green monkey COS7 cell membranes using CDP-star as substrate pretreated for 5 to 10 mins followed by substrate addition and measured after 15 to 20 mins by spectrophotometric method	ic50	1.2400	uM
(4-methyl-2-oxochromen-7-yl) 2,4,5-trichlorobenzenesulfonate	1444566: Inhibition of human IAP using CDP-star as substrate pretreated for 10 mins followed by substrate addition measured after 10 mins by spectrophotometric method	ic50	1.3300	uM
(3Z)-3-[(4-methoxyphenyl)methylidene]-1,1-dioxo-1lambda6,2-benzothiazin-4-one	1422553: Inhibition of human IAP expressed in African green monkey COS7 cell membranes using CDP-star as substrate pretreated for 5 to 10 mins followed by substrate addition and measured after 15 to 20 mins by spectrophotometric method	ic50	1.5300	uM
2-(3-phenylphenyl)-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	1.6700	uM
2-(3,4-dimethylphenyl)-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	1.7500	uM
(3Z)-3-benzylidene-1,1-dioxo-1lambda6,2-benzothiazin-4-one	1422553: Inhibition of human IAP expressed in African green monkey COS7 cell membranes using CDP-star as substrate pretreated for 5 to 10 mins followed by substrate addition and measured after 15 to 20 mins by spectrophotometric method	ic50	1.7800	uM
2-(4-ethoxyanilino)-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	2.0200	uM
(3-chloro-4-methyl-2-oxochromen-7-yl) 4-methoxybenzenesulfonate	1444566: Inhibition of human IAP using CDP-star as substrate pretreated for 10 mins followed by substrate addition measured after 10 mins by spectrophotometric method	ic50	2.1300	uM
2-[amino(methyl)amino]-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	2.2200	uM
(3-cyano-4-methyl-2-oxochromen-7-yl) 2,5-dichlorobenzenesulfonate	1444566: Inhibition of human IAP using CDP-star as substrate pretreated for 10 mins followed by substrate addition measured after 10 mins by spectrophotometric method	ic50	2.2600	uM
(3Z)-3-[(3-bromophenyl)methylidene]-1,1-dioxo-1lambda6,2-benzothiazin-4-one	1422553: Inhibition of human IAP expressed in African green monkey COS7 cell membranes using CDP-star as substrate pretreated for 5 to 10 mins followed by substrate addition and measured after 15 to 20 mins by spectrophotometric method	ic50	2.5500	uM
(4-methyl-2-oxochromen-7-yl) 4-chloro-3-nitrobenzenesulfonate	1444566: Inhibition of human IAP using CDP-star as substrate pretreated for 10 mins followed by substrate addition measured after 10 mins by spectrophotometric method	ic50	2.7200	uM
(3-cyano-4-methyl-2-oxochromen-7-yl) octane-1-sulfonate	1444566: Inhibition of human IAP using CDP-star as substrate pretreated for 10 mins followed by substrate addition measured after 10 mins by spectrophotometric method	ic50	2.8100	uM
(8-ethylsulfonyloxy-4-methyl-2-oxochromen-7-yl) ethanesulfonate	1444566: Inhibition of human IAP using CDP-star as substrate pretreated for 10 mins followed by substrate addition measured after 10 mins by spectrophotometric method	ic50	2.8700	uM
(4-methyl-8-nitro-2-oxochromen-7-yl) 4-octylbenzenesulfonate	1444566: Inhibition of human IAP using CDP-star as substrate pretreated for 10 mins followed by substrate addition measured after 10 mins by spectrophotometric method	ic50	3.0600	uM
(3Z)-3-[(4-fluorophenyl)methylidene]-1,1-dioxo-1lambda6,2-benzothiazin-4-one	1422553: Inhibition of human IAP expressed in African green monkey COS7 cell membranes using CDP-star as substrate pretreated for 5 to 10 mins followed by substrate addition and measured after 15 to 20 mins by spectrophotometric method	ic50	3.0600	uM
(3-chloro-4-methyl-2-oxochromen-7-yl) octane-1-sulfonate	1444566: Inhibition of human IAP using CDP-star as substrate pretreated for 10 mins followed by substrate addition measured after 10 mins by spectrophotometric method	ic50	3.1200	uM
[8-(2,5-dichlorophenyl)sulfonyloxy-4-methyl-2-oxochromen-7-yl] 2,5-dichlorobenzenesulfonate	1444566: Inhibition of human IAP using CDP-star as substrate pretreated for 10 mins followed by substrate addition measured after 10 mins by spectrophotometric method	ic50	3.2100	uM
(3-chloro-4-methyl-2-oxochromen-7-yl) butane-1-sulfonate	1444566: Inhibition of human IAP using CDP-star as substrate pretreated for 10 mins followed by substrate addition measured after 10 mins by spectrophotometric method	ic50	3.2200	uM
(3-chloro-4-methyl-2-oxochromen-7-yl) methanesulfonate	1444566: Inhibition of human IAP using CDP-star as substrate pretreated for 10 mins followed by substrate addition measured after 10 mins by spectrophotometric method	ic50	3.5800	uM
(3-cyano-4-methyl-2-oxochromen-7-yl) 4-methoxybenzenesulfonate	1444566: Inhibition of human IAP using CDP-star as substrate pretreated for 10 mins followed by substrate addition measured after 10 mins by spectrophotometric method	ic50	3.5900	uM
(3Z)-3-[(4-bromophenyl)methylidene]-1,1-dioxo-1lambda6,2-benzothiazin-4-one	1422553: Inhibition of human IAP expressed in African green monkey COS7 cell membranes using CDP-star as substrate pretreated for 5 to 10 mins followed by substrate addition and measured after 15 to 20 mins by spectrophotometric method	ic50	3.6900	uM
(3Z)-3-[(2-methylphenyl)methylidene]-1,1-dioxo-1lambda6,2-benzothiazin-4-one	1422553: Inhibition of human IAP expressed in African green monkey COS7 cell membranes using CDP-star as substrate pretreated for 5 to 10 mins followed by substrate addition and measured after 15 to 20 mins by spectrophotometric method	ic50	3.7500	uM
2-[2-(dimethylamino)ethylamino]-7-(trifluoromethyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one	1402702: Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	ic50	3.7500	uM
(3Z)-3-[(3-chlorophenyl)methylidene]-1,1-dioxo-1lambda6,2-benzothiazin-4-one	1422553: Inhibition of human IAP expressed in African green monkey COS7 cell membranes using CDP-star as substrate pretreated for 5 to 10 mins followed by substrate addition and measured after 15 to 20 mins by spectrophotometric method	ic50	3.7700	uM
(4-methyl-2-oxochromen-7-yl) 2-methyl-5-nitrobenzenesulfonate	1444566: Inhibition of human IAP using CDP-star as substrate pretreated for 10 mins followed by substrate addition measured after 10 mins by spectrophotometric method	ic50	3.9100	uM
(3-chloro-4-methyl-2-oxochromen-7-yl) 4-chloro-3-nitrobenzenesulfonate	1444566: Inhibition of human IAP using CDP-star as substrate pretreated for 10 mins followed by substrate addition measured after 10 mins by spectrophotometric method	ic50	4.0600	uM
(3-cyano-4-methyl-2-oxochromen-7-yl) ethanesulfonate	1444566: Inhibition of human IAP using CDP-star as substrate pretreated for 10 mins followed by substrate addition measured after 10 mins by spectrophotometric method	ic50	4.0600	uM
(3-chloro-4-methyl-2-oxochromen-7-yl) ethanesulfonate	1444566: Inhibition of human IAP using CDP-star as substrate pretreated for 10 mins followed by substrate addition measured after 10 mins by spectrophotometric method	ic50	4.1800	uM
(3Z)-3-[(4-chlorophenyl)methylidene]-1,1-dioxo-1lambda6,2-benzothiazin-4-one	1422553: Inhibition of human IAP expressed in African green monkey COS7 cell membranes using CDP-star as substrate pretreated for 5 to 10 mins followed by substrate addition and measured after 15 to 20 mins by spectrophotometric method	ic50	4.3500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	2
lasiocarpine	decreases expression	1
bisphenol A	increases methylation	1
deoxynivalenol	decreases activity, decreases expression	1
kojic acid	decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	increases expression	1
coumarin	decreases phosphorylation	1
5,6,7,8-tetrahydrofolic acid	decreases reaction, increases activity	1
cyanoginosin LR	decreases expression	1
fipronil	increases expression, affects cotreatment	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	increases activity, increases reaction	1
Wortmannin	increases activity, increases reaction	1
Adenosine	decreases reaction, increases activity	1
Air Pollutants	increases abundance, increases expression	1
Ascorbic Acid	affects cotreatment, decreases expression	1
Atrazine	increases expression	1
Butyrates	increases expression	1
Cadmium	affects cotreatment, increases expression	1
Cycloheximide	decreases activity	1
DEET	increases expression, affects cotreatment	1
Dietary Fats	increases activity	1
Estradiol	increases expression	1
Formaldehyde	decreases expression	1
Colforsin	decreases reaction, increases activity	1
Lead	increases expression, affects cotreatment	1
Methotrexate	increases activity, increases reaction, decreases reaction	1
Quercetin	affects cotreatment, decreases expression	1
Thymidine	increases activity, increases reaction	1
Tobacco Smoke Pollution	increases methylation	1

ChEMBL screening assays

21 unique, capped per target: 12 binding, 6 functional, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1054563	Binding	Inhibition of IAP by luminescent assay	Discovery and validation of a series of aryl sulfonamides as selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP). — J Med Chem
CHEMBL1738087	Functional	PUBCHEM_BIOASSAY: Dose Response confirmation of uHTS hits from a small molecule inhibitors of human intestinal alkaline phosphatase via a luminescent assay - Set 2. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):	PubChem BioAssay data set
CHEMBL4253711	ADMET	Inhibition of human IAP expressed in COS7 cells preincubated for 5 to 7 mins followed by CDP-star substrate addition measured after 15 to 20 mins by luminescence assay	2-Substituted 7-trifluoromethyl-thiadiazolopyrimidones as alkaline phosphatase inhibitors. Synthesis, structure activity relationship and molecular docking study. — Eur J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00167882	PHASE4	COMPLETED	The Influence of 5-Aminosalicylates on Thiopurine Metabolite Levels
NCT00205062	PHASE4	TERMINATED	Positron Emission Tomography (PET)-Computed Tomography (CT) in Inflammatory Bowel Disease (IBD)
NCT00567593	PHASE4	COMPLETED	Gene Regulation by Thiazolidinediones
NCT00746395	PHASE4	COMPLETED	Randomized, Placebo-controlled Trial of Lubiprostone as a Preparation for Capsule Endoscopy
NCT01034358	PHASE4	COMPLETED	Immune Response to the Human Papillomavirus Vaccine in Young Women With Inflammatory Bowel Disease
NCT01056913	PHASE4	COMPLETED	NITI CAR27 (ColonRing) Compression Anastomosis in Colorectal Surgery
NCT01067547	PHASE4	COMPLETED	A Trial of Iron Replacement in Patients With Iron Deficiency.
NCT01341808	PHASE4	COMPLETED	Immunogenicity of Hepatitis A Vaccine in Inflammatory Bowel Disease (IBD) Patients
NCT01908283	PHASE4	COMPLETED	Induction of Immunity Against Streptococcus Pneumoniae in Adults With Inflammatory Bowel Disease
NCT01934088	PHASE4	COMPLETED	Satisfaction With Nurse Administered Propofol Sedation vs. Midazolam With Fentanyl Sedation for Endoscopy
NCT02162862	PHASE4	COMPLETED	Treating Disrupted Sleep in Individuals With Inflammatory Bowel Disease
NCT02248337	PHASE4	COMPLETED	Low Volume Colon Preparation for IBD
NCT02281799	PHASE4	WITHDRAWN	Thiopurine Induced Pancreatitis in IBD Patients
NCT02392286	PHASE4	TERMINATED	Corticosteroid Dosage for Crohn’s Disease Flare
NCT02437591	PHASE4	COMPLETED	Study to Evaluate the Pharmacokinetics of Fidaxomicin in Inflammatory Bowel Disease (IBD) Subjects With Clostridium Difficile Infection (CDI)
NCT02453776	PHASE4	COMPLETED	Precision Dosing of Infliximab Versus Conventional Dosing of Infliximab
NCT02461758	PHASE4	COMPLETED	Trial of High Dose vs. Standard Dose Influenza Vaccine in Inflammatory Bowel Disease Patients
NCT02566889	PHASE4	TERMINATED	An Efficacy and Safety Study of Infliximab Dose Escalation in Pediatric Participants With Inflammatory Bowel Disease
NCT02774057	PHASE4	UNKNOWN	Trial of Captafer® vs. Oral Iron Sulfate in the Treatment of Iron Deficiency Anemia in Patients With IBD
NCT02806206	PHASE4	UNKNOWN	Prucalopride Prior to Small Bowel Capsule Endoscopy
NCT02946203	PHASE4	COMPLETED	Comparison of VoLumen and Breeza Oral Contrast Agents in Pediatric Patients
NCT02994836	PHASE4	COMPLETED	GIS-SUSANTI-TNF-2015 (Anti-TNF Discontinuation )
NCT03220841	PHASE4	UNKNOWN	Stricture Definition and Treatment (STRIDENT) Drug Therapy Study
NCT03351972	PHASE4	COMPLETED	Differences in Preparation for Small Bowel Capsule Endoscopy
NCT03466983	PHASE4	COMPLETED	A Trial Comparing the Incidence of Hypophosphatemia in Relation to Treatment With Iron Isomaltoside and Ferric Carboxymaltose in Subjects With Iron Deficiency Anaemia Due to Inflammatory Bowel Disease
NCT03591770	PHASE4	TERMINATED	Shingrix Vaccine in Patients With Moderate to Severe Ulcerative Colitis on Tofacitinib
NCT03629379	PHASE4	COMPLETED	Response to Ustekinumab for Anti-tnf Induced Psoriasiform Skin Lesions
NCT03723447	PHASE4	COMPLETED	Intraoperative TAP Block With Bupivacaine/Dexamethasone Against Liposomal Bupivacaine (Exparel®)
NCT03798691	PHASE4	COMPLETED	Immunogenicity of Herpes Zoster Subunit Vaccine in Inflammatory Bowel Disease Patients Treated With Vedolizumab
NCT03860012	PHASE4	UNKNOWN	Folic Acid in Pediatric Inflammatory Bowel Disease
NCT03885713	PHASE4	COMPLETED	Identification of Predictive Biomarkers for Response to Biologic Therapies and Tofacitinib in Inflammatory Bowel Disease
NCT03917303	PHASE4	RECRUITING	Control Crohn Safe Trial
NCT04045782	PHASE4	COMPLETED	Evaluation of the Safety and Effectiveness of Switching From Humira® to Imraldi® in Flanders
NCT04304950	PHASE4	COMPLETED	Chronotherapy in Inflammatory Bowel Disease
NCT04626947	PHASE4	TERMINATED	Prevention of Recurrent Clostridium Difficile Infection (CDI) in Patients With Inflammatory Bowel Disease (IBD).
NCT04646187	PHASE4	ENROLLING_BY_INVITATION	De-escalation of Anti-TNF Therapy in Inflammatory Bowel Disease
NCT04835506	PHASE4	ACTIVE_NOT_RECRUITING	Proactive Infliximab Optimization Using a Pharmacokinetic Dashboard Versus Standard of Care in Patients With Inflammatory Bowel Disease: The OPTIMIZE Trial
NCT04982172	PHASE4	COMPLETED	Model-informed Dose De-escalation of Infliximab in Patients With Inflammatory Bowel Diseases
NCT05180175	PHASE4	COMPLETED	The Nordic IBD Treatment Strategy Trial
NCT05280405	PHASE4	UNKNOWN	Early Proactive Therapeutic Drug Monitoring of Infliximab in Children: EPIC Study