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): 167 total — 1 likely-pathogenic
• GTEx eGene: eQTL in 1 tissue, sQTL in 0 (q < 0.05)
• ChEMBL bioactivity: 5 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.16 (unconstrained)
• MANE Select transcript: NM_001631
• Notable: 167 clinical variants but no curated precision-oncology (CIViC) evidence yet

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

MANE Select: ENST00000295463

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 5: 1

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.

Highest expression (Bgee): jejunal mucosa, duodenum, ileal mucosa, ileum, small intestine.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ALPI is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 1 tissue and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

1 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Colon Transverse	eqtl	5.1e-04	-0.19	2:232456931:C:T

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

showing 100 of 278 tissues 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
biceps brachii	UBERON:0001507	59.35	gold quality
medial globus pallidus	UBERON:0002477	57.85	gold quality
gingiva	UBERON:0001828	57.75	gold quality
inferior olivary complex	UBERON:0002127	57.67	gold quality
lateral nuclear group of thalamus	UBERON:0002736	57.55	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	57.51	gold quality
heart right ventricle	UBERON:0002080	57.50	gold quality
trabecular bone tissue	UBERON:0002483	57.17	gold quality
myocardium	UBERON:0002349	57.13	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	56.77	gold quality
substantia nigra pars compacta	UBERON:0001965	56.71	gold quality
endothelial cell	CL:0000115	56.25	gold quality
globus pallidus	UBERON:0001875	56.00	gold quality
cartilage tissue	UBERON:0002418	55.99	gold quality
seminal vesicle	UBERON:0000998	55.51	gold quality
vena cava	UBERON:0004087	55.50	gold quality
nasal cavity epithelium	UBERON:0005384	55.42	gold quality
squamous epithelium	UBERON:0006914	54.93	gold quality
adult mammalian kidney	UBERON:0000082	54.44	gold quality
large intestine	UBERON:0000059	53.79	gold quality
epithelium of esophagus	UBERON:0001976	53.74	gold quality
esophagus squamous epithelium	UBERON:0006920	53.61	gold quality
oviduct epithelium	UBERON:0004804	53.34	gold quality
colon	UBERON:0001155	53.28	gold quality
lateral globus pallidus	UBERON:0002476	53.06	gold quality
decidua	UBERON:0002450	52.50	gold quality
Brodmann (1909) area 23	UBERON:0013554	52.45	gold quality
entorhinal cortex	UBERON:0002728	52.14	gold quality
substantia nigra pars reticulata	UBERON:0001966	51.94	gold quality
postcentral gyrus	UBERON:0002581	51.64	gold quality
kidney	UBERON:0002113	51.48	gold quality
skeletal muscle tissue	UBERON:0001134	51.44	gold quality
middle temporal gyrus	UBERON:0002771	51.39	gold quality
muscle tissue	UBERON:0002385	51.00	gold quality
deltoid	UBERON:0001476	50.82	gold quality
metanephric glomerulus	UBERON:0004736	50.76	gold quality
cauda epididymis	UBERON:0004360	50.58	gold quality
renal glomerulus	UBERON:0000074	50.00	gold quality
corpus epididymis	UBERON:0004359	50.00	gold quality
parietal lobe	UBERON:0001872	49.86	gold quality
caput epididymis	UBERON:0004358	49.52	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.52	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
orbitofrontal cortex	UBERON:0004167	49.27	gold quality
kidney epithelium	UBERON:0004819	49.26	gold quality
colonic epithelium	UBERON:0000397	49.22	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
smooth muscle tissue	UBERON:0001135	48.99	gold quality
body of tongue	UBERON:0011876	48.94	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
male germ cell	CL:0000015	48.86	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
epithelium of bronchus	UBERON:0002031	48.80	gold quality
epithelial cell of pancreas	CL:0000083	48.74	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
nephron tubule	UBERON:0001231	48.52	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
bronchus	UBERON:0002185	48.48	gold quality
thymus	UBERON:0002370	48.38	gold quality
sperm	CL:0000019	48.37	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
superior frontal gyrus	UBERON:0002661	48.15	gold quality
amniotic fluid	UBERON:0000173	48.14	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
adult organism	UBERON:0007023	48.04	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
bronchial epithelial cell	CL:0002328	47.40	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

HPA expression

RNA tissue specificity: Tissue enriched

7 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Duodenum	tissue	133.1	high
Small intestine	tissue	120.6	high
Colon	tissue	4.1	medium
Rectum	tissue	3.6	high
Kidney	tissue	0.9	not detected
Smooth muscle	tissue	0.5	not detected
Stomach 1	tissue	0.3	not detected

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

Targeting ALPI by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 74 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 3.42e-16, LOEUF 1.16, missense Z 0.529 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000295463 — one region, missense o/e 0.96.

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)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	P09487	91.0%	Diamond
Felis catus	Q29486	91.0%	Diamond
Gallus gallus	Q92058	78.0%	Diamond
Gadus morhua	P83456	76.8%	Diamond
Bacillus subtilis subsp. subtilis str. 168	P19405	59.7%	Diamond
Bombyx mori	P29523	48.1%	Diamond
Saccharomyces cerevisiae S288C	P11491	47.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ALPG	protein-coding	251
CHRND	protein-coding	1144
PRSS56	protein-coding	646960
ECEL1	protein-coding	9427

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

Enzyme classification (BRENDA)

• EC 3.1.3.1 — alkaline phosphatase (BRENDA: 134 organisms, 346 substrates, 667 inhibitors, 331 Km, 180 kcat entries)

Substrate kinetics (BRENDA)

32 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-NITROPHENYL PHOSPHATE	—	218
P-NITROPHENYL PHOSPHATE	0.0094–5.02	37
PHENYL PHOSPHATE	6.1–101.2	13
3-(4-METHOXYSPIRO [1,2-DIOXETANE-3,2’-(5’-CHLORO	0.037–0.1159	7
BETA-GLYCEROPHOSPHATE	0.3–3.35	7
ATP	0.1–5.7	5
DIPHOSPHATE	0.12–4	5
2-CHLORO-5-(4-METHOXYSPIRO (1,2-DIOXETANE-3,2’-(	0.01–0.177	3
2-NAPHTHYL PHOSPHATE	0.026–0.078	2
ADP	2.26–4.4	2
GLUCOSE 1-PHOSPHATE	2.22–4.8	2
PHOSPHO-DL-THR	0.39–0.9	2
PHOSPHO-DL-TYR	0.4–0.72	2
PHOSPHO-L-SER	0.38–0.68	2
PYRIDOXAL PHOSPHATE	0.2–0.37	2

Catalyzed reactions (Rhea)

• 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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane

Antibody reliability (HPA): IH supported · IF approved

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)

Position	Role
111	phosphoserine intermediate

Ligand- & substrate-binding residues (14)

Position	Role
289	Ca(2+)
304	Ca(2+)
330	Mg(2+)
335	Zn(2+)
339	Zn(2+)
376	Zn(2+)
377	Zn(2+)
451	Zn(2+)
61	Mg(2+)
61	Zn(2+)
111	Zn(2+)
174	Mg(2+)
235	Ca(2+)
288	Ca(2+)

Post-translational modifications (1)

Type	Positions
Gpi-anchor amidated aspartate	503

Disulfide bonds (2)

Type	Positions
Disulfide bond	140–202, 486–493

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	141, 268, 429

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 10; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

10 pathways:

ID	Pathway	Evidence
R-HSA-8935690	Digestion	curated
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins	curated
R-HSA-1483166	Synthesis of PA	curated
R-HSA-8963743	Digestion and absorption	—
R-HSA-1483206	Glycerophospholipid biosynthesis	—
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-1483257	Phospholipid metabolism	—
R-HSA-597592	Post-translational protein modification	—

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 (3): extracellular region (GO:0005576), plasma membrane (GO:0005886), side of membrane (GO:0098552)

Reactome top-level categories

7 top-level categories:

Category	Pathways
Glycerophospholipid biosynthesis	1
Post-translational protein modification	1
Digestion and absorption	1
Phospholipid metabolism	1
Metabolism of lipids	1
Metabolism	1
Metabolism of proteins	1

GO top-level categories

13 GO namespaces:

Category	Terms
cellular anatomical structure	2
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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 12 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
protease binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,628 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALPI	CHRND	Q07001	772
ALPI	INHA	P05111	758
ALPI	BGLAP	P02818	715
ALPI	PAX3	P23760	700
ALPI	COL4A3	Q01955	676
ALPI	GPT	P24298	674
ALPI	RUNX2	Q13950	655
ALPI	ALB	P02768	651
ALPI	GAPDH	P00354	600
ALPI	GOT1L1	Q8NHS2	600
ALPI	EXO1	Q9UQ84	596
ALPI	PAX7	P23759	585
ALPI	NANOG	Q9H9S0	552
ALPI	SPP1	P10451	549
ALPI	SP7	Q8TDD2	548

IntAct

Human interaction partners of ALPI in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

7 partners by confidence:

Partner	Interaction type	MIscore	Records
NOTCH2NLA	physical association	0.670	4
KRTAP10-8	physical association	0.560	3
KRTAP10-9	physical association	0.560	3
ALPP	association	0.530	2
HSPB1	physical association	0.370	1
RTCA	association	0.350	1
EIF4A2	physical association	0.000	1

BioGRID (85 interactions; top human partners by supporting records): IRF5 (Affinity Capture-MS; 4 records), ALPP (Affinity Capture-MS; 3 records), ALPPL2 (Affinity Capture-MS; 2 records), ARF5 (Affinity Capture-MS; 2 records), ARL2 (Affinity Capture-MS; 2 records), DDX19B (Affinity Capture-MS; 2 records), RAB39B (Affinity Capture-MS; 2 records), RDH13 (Affinity Capture-MS; 2 records), TUBB1 (Affinity Capture-MS; 2 records), ABCB6 (Affinity Capture-MS), ABCF2 (Affinity Capture-MS), ARL8A (Affinity Capture-MS), ARL8B (Affinity Capture-MS), ART5 (Affinity Capture-MS), AURKB (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for ALPI: 167 ClinVar records (1 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	92
Likely benign	60
Benign	12

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1335447	NM_001631.5(ALPI):c.1315C>T (p.Gln439Ter)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ALPI’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 513):

Position(s)	Effect	Δscore	Sites
2:232456466–232456467	donor_loss	1.0000	5
2:232456696–232456697	donor_loss	1.0000	5
2:232456897	acceptor_loss	1.0000	2
2:232457074–232457075	donor_loss	1.0000	5
2:232457563	acceptor_loss	1.0000	2
2:232457564	acceptor_gain	1.0000
2:232457680	donor_gain	1.0000
2:232457700–232457701	donor_loss	1.0000	5
2:232457793–232457794	acceptor_loss	1.0000	2
2:232457996–232457997	acceptor_loss	1.0000	6

AlphaMissense

1,209 missense substitutions predicted likely pathogenic (of 3,423 scored), across 314 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D335	8	0.991	0.998
H339	8	0.983	0.993
D376	8	0.983	0.994
H377	8	0.982	0.992
D61	8	0.977	0.994
H379	8	0.976	0.992
H451	8	0.975	0.991
D455	8	0.967	0.996
S111	8	0.958	0.996
D204	8	0.953	0.987
H338	8	0.944	0.987
F288	8	0.923	0.973
D110	8	0.919	0.984
D403	8	0.915	0.976
H172	8	0.887	0.979
F58	8	0.878	0.977
D233	8	0.858	0.920
F381	8	0.848	0.963
F328	8	0.838	0.922
D91	8	0.837	0.971

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Kidney Renal Clear Cell Carcinoma, Liver Hepatocellular Carcinoma)

Disease associations

OMIM: gene MIM:171740 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
inflammatory bowel disease	Moderate	Autosomal recessive

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
COVID-19 research	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green

Mondo (1): inflammatory bowel disease (MONDO:0005265)

GWAS associations

3 associations:

Study	Trait	p-value
GCST010002_411	Refractive error	1e-123
GCST003944_11	Hepcidin/ferritin ratio	7e-7
GCST003944_26	Hepcidin/ferritin ratio	2e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0007901	hepcidin:ferritin ratio

MeSH disease descriptors

1 disease descriptors:

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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 694,844 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

5 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1454	LEVAMISOLE	4	56,923
CHEMBL140	CURCUMIN	3	95,185
CHEMBL301523	PHENYLALANINE	3	537,013
CHEMBL250450	ISOQUERCETIN	2	1,676
CHEMBL442687	TIOXOLONE	2	4,047

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

314 measured of 514 human assays (547 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
CHEMBL4284174	IC50	210 nM
CHEMBL4282304	IC50	250 nM
CHEMBL4291826	IC50	280 nM
CHEMBL4281930	IC50	290 nM
CHEMBL4289799	IC50	330 nM
CHEMBL4283860	IC50	380 nM
(2-anilinopyrimidin-4-yl)-phenyl-amine	IC50	423 nM	US-9249124: Aurora kinase inhibitors and methods of making and using thereof
CHEMBL4285299	IC50	450 nM
CHEMBL4286723	IC50	520 nM
CHEMBL4294808	IC50	520 nM
CHEMBL4281206	IC50	540 nM
CHEMBL4287459	IC50	560 nM
CHEMBL4103223	IC50	580 nM
CHEMBL4277341	IC50	610 nM
CHEMBL4279537	IC50	620 nM
CHEMBL4287165	IC50	660 nM
cid_25199559	EC50	663 nM
cid_4879299	EC50	718 nM
CHEMBL4060753	IC50	850 nM
CHEMBL4281863	IC50	880 nM
CHEMBL4095459	IC50	920 nM
CHEMBL4090465	IC50	920 nM
CHEMBL4292887	IC50	930 nM
CHEMBL4292054	IC50	1060 nM
6-(2-fluorophenyl)-2-[4-(2-hydroxyethyl)-3-methyl-5-oxo-2,5-dihydro-1H-pyrazol-1-yl]-4(3H)-pyrimidinone	IC50	1070 nM
CHEMBL4284091	IC50	1120 nM
CHEMBL4288407	IC50	1150 nM
CHEMBL4077330	IC50	1170 nM
1-(3,4-dihydroxyphenyl)-2-(4,6-dimethylpyrimidin-2-ylthio)ethanone	IC50	1210 nM
CHEMBL4079164	IC50	1250 nM
CHEMBL4069435	IC50	1330 nM
CHEMBL4087225	IC50	1330 nM
CHEMBL4287104	IC50	1350 nM
CHEMBL4281616	IC50	1390 nM
CHEMBL4068298	IC50	1420 nM
CHEMBL4276925	IC50	1430 nM
CHEMBL4292485	IC50	1440 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
CHEMBL4288640	IC50	1530 nM
CHEMBL4276768	IC50	1530 nM
CHEMBL4295150	IC50	1580 nM
3-[6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-5-phenyl-pentanoic acid	IC50	1610 nM
CHEMBL4084312	IC50	1640 nM
1,8-Dihydroxy-3-hydroxymethyl-anthraquinone	IC50	1770 nM
MLS000102658	EC50	1910 nM
CHEMBL4075025	IC50	1940 nM
CHEMBL4287221	IC50	1980 nM
4-(2-benzylsulfanylethyl)pyridine;phosphoric acid	IC50	2010 nM
CHEMBL4280737	IC50	2020 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 126 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 expression, decreases activity	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	affects cotreatment, increases expression	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 expression, increases abundance	1
Ascorbic Acid	affects cotreatment, decreases expression	1
Atrazine	increases expression	1
Butyrates	increases expression	1
Cadmium	increases expression, affects cotreatment	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	affects cotreatment, increases expression	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00167882	Phase 4	COMPLETED	The Influence of 5-Aminosalicylates on Thiopurine Metabolite Levels
NCT00205062	Phase 4	TERMINATED	Positron Emission Tomography (PET)-Computed Tomography (CT) in Inflammatory Bowel Disease (IBD)
NCT00567593	Phase 4	COMPLETED	Gene Regulation by Thiazolidinediones
NCT00746395	Phase 4	COMPLETED	Randomized, Placebo-controlled Trial of Lubiprostone as a Preparation for Capsule Endoscopy
NCT01034358	Phase 4	COMPLETED	Immune Response to the Human Papillomavirus Vaccine in Young Women With Inflammatory Bowel Disease
NCT01056913	Phase 4	COMPLETED	NITI CAR27 (ColonRing) Compression Anastomosis in Colorectal Surgery
NCT01067547	Phase 4	COMPLETED	A Trial of Iron Replacement in Patients With Iron Deficiency.
NCT01341808	Phase 4	COMPLETED	Immunogenicity of Hepatitis A Vaccine in Inflammatory Bowel Disease (IBD) Patients
NCT01908283	Phase 4	COMPLETED	Induction of Immunity Against Streptococcus Pneumoniae in Adults With Inflammatory Bowel Disease
NCT01934088	Phase 4	COMPLETED	Satisfaction With Nurse Administered Propofol Sedation vs. Midazolam With Fentanyl Sedation for Endoscopy
NCT02162862	Phase 4	COMPLETED	Treating Disrupted Sleep in Individuals With Inflammatory Bowel Disease
NCT02248337	Phase 4	COMPLETED	Low Volume Colon Preparation for IBD
NCT02281799	Phase 4	WITHDRAWN	Thiopurine Induced Pancreatitis in IBD Patients
NCT02392286	Phase 4	TERMINATED	Corticosteroid Dosage for Crohn’s Disease Flare
NCT02437591	Phase 4	COMPLETED	Study to Evaluate the Pharmacokinetics of Fidaxomicin in Inflammatory Bowel Disease (IBD) Subjects With Clostridium Difficile Infection (CDI)
NCT02453776	Phase 4	COMPLETED	Precision Dosing of Infliximab Versus Conventional Dosing of Infliximab
NCT02461758	Phase 4	COMPLETED	Trial of High Dose vs. Standard Dose Influenza Vaccine in Inflammatory Bowel Disease Patients
NCT02566889	Phase 4	TERMINATED	An Efficacy and Safety Study of Infliximab Dose Escalation in Pediatric Participants With Inflammatory Bowel Disease
NCT02774057	Phase 4	UNKNOWN	Trial of Captafer® vs. Oral Iron Sulfate in the Treatment of Iron Deficiency Anemia in Patients With IBD
NCT02806206	Phase 4	UNKNOWN	Prucalopride Prior to Small Bowel Capsule Endoscopy
NCT02946203	Phase 4	COMPLETED	Comparison of VoLumen and Breeza Oral Contrast Agents in Pediatric Patients
NCT02994836	Phase 4	COMPLETED	GIS-SUSANTI-TNF-2015 (Anti-TNF Discontinuation )
NCT03220841	Phase 4	UNKNOWN	Stricture Definition and Treatment (STRIDENT) Drug Therapy Study
NCT03351972	Phase 4	COMPLETED	Differences in Preparation for Small Bowel Capsule Endoscopy
NCT03466983	Phase 4	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	Phase 4	TERMINATED	Shingrix Vaccine in Patients With Moderate to Severe Ulcerative Colitis on Tofacitinib
NCT03629379	Phase 4	COMPLETED	Response to Ustekinumab for Anti-tnf Induced Psoriasiform Skin Lesions
NCT03723447	Phase 4	COMPLETED	Intraoperative TAP Block With Bupivacaine/Dexamethasone Against Liposomal Bupivacaine (Exparel®)
NCT03798691	Phase 4	COMPLETED	Immunogenicity of Herpes Zoster Subunit Vaccine in Inflammatory Bowel Disease Patients Treated With Vedolizumab
NCT03860012	Phase 4	UNKNOWN	Folic Acid in Pediatric Inflammatory Bowel Disease
NCT03885713	Phase 4	COMPLETED	Identification of Predictive Biomarkers for Response to Biologic Therapies and Tofacitinib in Inflammatory Bowel Disease
NCT03917303	Phase 4	RECRUITING	Control Crohn Safe Trial
NCT04045782	Phase 4	COMPLETED	Evaluation of the Safety and Effectiveness of Switching From Humira® to Imraldi® in Flanders
NCT04304950	Phase 4	COMPLETED	Chronotherapy in Inflammatory Bowel Disease
NCT04626947	Phase 4	TERMINATED	Prevention of Recurrent Clostridium Difficile Infection (CDI) in Patients With Inflammatory Bowel Disease (IBD).
NCT04646187	Phase 4	ENROLLING_BY_INVITATION	De-escalation of Anti-TNF Therapy in Inflammatory Bowel Disease
NCT04835506	Phase 4	ACTIVE_NOT_RECRUITING	Proactive Infliximab Optimization Using a Pharmacokinetic Dashboard Versus Standard of Care in Patients With Inflammatory Bowel Disease: The OPTIMIZE Trial
NCT04982172	Phase 4	COMPLETED	Model-informed Dose De-escalation of Infliximab in Patients With Inflammatory Bowel Diseases
NCT05180175	Phase 4	COMPLETED	The Nordic IBD Treatment Strategy Trial
NCT05280405	Phase 4	UNKNOWN	Early Proactive Therapeutic Drug Monitoring of Infliximab in Children: EPIC Study
NCT05340764	Phase 4	COMPLETED	Safety of Reduced Infliximab Infusion Time
NCT05439772	Phase 4	COMPLETED	Examining the Effect of Ondansetron on Bowel Prep Success
NCT05456932	Phase 4	UNKNOWN	Predicting Response to Iron Supplementation in Patients With Active Inflammatory Bowel Disease
NCT06055543	Phase 4	UNKNOWN	Impact of a New Plant-based High-energy Oral Nutritional Supplement on Nutritional Outcomes in Malnourished Patients
NCT06113913	Phase 4	RECRUITING	Subcutaneous Infliximab After A Previous Intravenous Dose Optimization
NCT06224270	Phase 4	WITHDRAWN	Study of Response to Zoster Vaccine in Adults with Inflammatory Bowel Disease Treated with Medications
NCT06346288	Phase 4	COMPLETED	A Study to Assess the Concentrations of Risankizumab in the Breast Milk of Adult Lactating Women With Inflammatory Bowel Disease
NCT06584162	Phase 4	RECRUITING	Subcutaneous Interval Lengthening of Vedolizumab for Economic Research
NCT06788340	Phase 4	NOT_YET_RECRUITING	MOdel-Informed Precision Dosing of Ustekinumab and VEdolizumab in Inflammatory Bowel Disease
NCT06794944	Phase 4	NOT_YET_RECRUITING	Use of Fidaxomicin Compared to Vancomycin for Decolonization of C. Difficile in Patients With Inflammatory Bowel Disease
NCT07161297	Phase 4	NOT_YET_RECRUITING	Remimazolam for Colonoscopy in IBD Patients
NCT07612267	Phase 4	RECRUITING	A Study to Measure Mirikizumab Levels in Breast Milk of Lactating Participants Receiving Mirikizumab Therapeutically for an Approved Indication
NCT07673497	Phase 4	COMPLETED	Can Vitamin D Replacement Correct Chronic Disease Anemia?
NCT07737665	Phase 4	RECRUITING	Efficacy of Melatonin Treatment on Sleep Quality Improvement in Inflammatory Bowel Disease Patients With Clinical Remission
NCT00175292	Phase 3	COMPLETED	A Randomized Controlled Trial of VSL#3 for the Prevention of Endoscopic Recurrence Following Surgery for Crohn’s Disease.
NCT00237653	Phase 3	TERMINATED	MICI-CMV:Valganciclovir in Recurrent Bouts of Cryptogenic Inflammatory Bowel Diseases With an Infection by Cytomegalovirus
NCT00321412	Phase 3	COMPLETED	Safety and Efficacy of AST-120 in Mild to Moderate Crohn’s Patients With Fistulas
NCT00408174	Phase 3	COMPLETED	Balsalazide Disodium vs. Mesalamine in Mildly to Moderately Active Ulcerative Colitis
NCT00486031	Phase 3	COMPLETED	Open-Label, Long-term Balsalziade Disodium Tablet Ulcerative Colitis Study
NCT00620126	Phase 3	COMPLETED	The Home Telemanagement (UC HAT) Trial for Patients With Ulcerative Colitis

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ALPI across ~30M SureChEMBL compounds — explore on Sugi Predict.