CHI3L1

Summary

CHI3L1 (chitinase 3 like 1, HGNC:1932) is a protein-coding gene on chromosome 1q32.1, encoding Chitinase-3-like protein 1 (P36222). Carbohydrate-binding lectin with a preference for chitin.

Chitinases catalyze the hydrolysis of chitin, which is an abundant glycopolymer found in insect exoskeletons and fungal cell walls. The glycoside hydrolase 18 family of chitinases includes eight human family members. This gene encodes a glycoprotein member of the glycosyl hydrolase 18 family. The protein lacks chitinase activity and is secreted by activated macrophages, chondrocytes, neutrophils and synovial cells. The protein is thought to play a role in the process of inflammation and tissue remodeling.

Source: NCBI Gene 1116 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schizophrenia (No Known Disease Relationship, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 106 total
• Phenotypes (HPO): 7
• Druggable target: yes
• MANE Select transcript: NM_001276

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1932
Approved symbol	CHI3L1
Name	chitinase 3 like 1
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	GP39, YKL40, YK-40
Ensembl gene	ENSG00000133048
Ensembl biotype	protein_coding
OMIM	601525
Entrez	1116

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 3 retained_intron

ENST00000255409, ENST00000404436, ENST00000472064, ENST00000473185, ENST00000478742, ENST00000874774, ENST00000874776, ENST00000874777, ENST00000874778, ENST00000874779, ENST00000874780, ENST00000874781, ENST00000946568, ENST00000946569, ENST00000946570

RefSeq mRNA: 1 — MANE Select: NM_001276 NM_001276

CCDS: CCDS1435

Canonical transcript exons

ENST00000255409 — 10 exons

Exon	Start	End
ENSE00001045180	203178931	203179585
ENSE00001045185	203179761	203179877
ENSE00001045187	203180470	203180652
ENSE00001918937	203186599	203186704
ENSE00002206594	203186316	203186345
ENSE00002219779	203183641	203183791
ENSE00002314206	203185184	203185385
ENSE00002314519	203182731	203182852
ENSE00002317562	203184576	203184632
ENSE00003563608	203181162	203181285

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 99.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 307.5544 / max 34189.0090, expressed in 1015 samples.

FANTOM5 promoters (32 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16805	266.3193	963
16806	31.8144	596
16800	1.5195	256
16773	0.8864	198
16772	0.8723	198
16774	0.7944	193
201886	0.6953	183
201887	0.3778	194
16780	0.3483	121
16783	0.3328	129

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pericardium	UBERON:0002407	99.62	gold quality
cartilage tissue	UBERON:0002418	99.06	gold quality
upper leg skin	UBERON:0004262	97.99	gold quality
mammalian vulva	UBERON:0000997	97.71	gold quality
renal glomerulus	UBERON:0000074	97.64	gold quality
inferior olivary complex	UBERON:0002127	97.53	gold quality
metanephric glomerulus	UBERON:0004736	97.25	gold quality
lateral globus pallidus	UBERON:0002476	97.04	gold quality
medial globus pallidus	UBERON:0002477	96.94	gold quality
bone marrow	UBERON:0002371	96.87	gold quality
globus pallidus	UBERON:0001875	96.76	gold quality
upper arm skin	UBERON:0004263	96.74	gold quality
trabecular bone tissue	UBERON:0002483	96.68	gold quality
tendon of biceps brachii	UBERON:0008188	96.61	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	95.77	gold quality
skin of leg	UBERON:0001511	95.74	gold quality
skin of abdomen	UBERON:0001416	95.62	gold quality
synovial joint	UBERON:0002217	95.57	gold quality
zone of skin	UBERON:0000014	95.53	gold quality
amniotic fluid	UBERON:0000173	95.52	gold quality
substantia nigra	UBERON:0002038	95.29	gold quality
pons	UBERON:0000988	95.14	gold quality
midbrain	UBERON:0001891	94.92	gold quality
blood	UBERON:0000178	94.89	gold quality
caudate nucleus	UBERON:0001873	94.84	gold quality
bone element	UBERON:0001474	94.52	gold quality
putamen	UBERON:0001874	94.29	gold quality
bone marrow cell	CL:0002092	94.17	gold quality
vermiform appendix	UBERON:0001154	94.11	gold quality
nipple	UBERON:0002030	94.11	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-9435	yes	12909.42
E-MTAB-9801	yes	7181.82
E-HCAD-11	yes	1236.40
E-CURD-114	yes	24.55
E-CURD-46	yes	15.58
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MAX, MYC, NFIX, NFKB, PITX2, SP1, STAT3, STAT6

miRNA regulators (miRDB)

27 targeting CHI3L1, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-3161	98.71	67.14	816
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-1265	98.36	66.46	598
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-3670	97.88	64.39	763
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-6824-5P	97.41	68.43	583
HSA-MIR-6835-5P	95.81	64.27	500
HSA-MIR-6732-5P	93.97	64.65	422

Literature-anchored findings (GeneRIF, showing 40)

• YKL-40 is elevated in cerebrospinal fluid from patients with purulent meningitis (PMID:11986266)
• elevated serum levels in patients with Streptococcus pneumoniae bacteremia and associated with the outcome of the disease (PMID:12069012)
• The chitinase 3-like protein human cartilage glycoprotein 39 (HC-gp39) stimulates proliferation of human connective-tissue cells and activates both extracellular signal-regulated kinase- and protein kinase B-mediated signalling pathways. (PMID:12071845)
• human chitinase 3-like 2 gene (YKL-39) but not chitinase 3-like 1 gene (YKL-40) is upregulated in osteoarthritic cartilage (PMID:12435396)
• HC-GP39 complexed with HLA-DR alpha beta 1*0401 is localized and presented on dendritic cells in the synovial tissue of rheumatoid arthritis patients. (PMID:12759455)
• CHI3L1 has profound effects on vascular smooth muscle cell (VSMC) migration but no effect on fibroblast migration. In addition, CHI3L1 adsorbed to polystyrene surfaces directly promotes VSMC attachment and spreading. (PMID:12799184)
• chitin or a closely related oligosaccharide could act as the physiological ligand for HCgp-39. (PMID:12851408)
• results indicated a predominant role for a single Sp1 binding site in regulating human cartilage-gp39 promoter activity in macrophages (PMID:12933821)
• upregulgated in glioblstoma multiforme. (PMID:12957359)
• High levels of serum YKL-40 reflect aggressiveness of metastatic breast cancer (PMID:14555515)
• the presence of HC gp-39-specific immune responses in healthy individuals may have an inhibitory effect on inflammatory responses in areas where HC gp-39 is present, and the response in rheumatoid arthritis has shifted toward a proinflammatory phenotype (PMID:15569925)
• Down-regulation of YKL-40 is associated with gliomas (PMID:15788675)
• YKL-40 may have role in neoplasm invasiveness; protein could stimulate fibroblast proliferation, promote angiogenesis, and protect cancer and/or stromal cells against apoptosis (PMID:15829322)
• Findings implicate YKL-40 as an important marker of therapeutic response and genetic subtype in glioblastomas and suggest that it may play an oncogenic role in these tumors. (PMID:15867231)
• induction and continued secretion of CHI3L1 in chondrocytes require sustained activation of NF-kappaB (PMID:16234240)
• The YKL-40 expression was associated with the expressions of p-MAPK, p-mTOR, and p-p70S6K (all P < 0.02), with a trend toward association with p-Akt expression (P = 0.095). (PMID:16818690)
• This article reviews the studies of YKL-40 with focus on a possible role of YKL-40 in insulin resistance, endothelial dysfunction and atherosclerosis. (PMID:16955240)
• Once-weekly intranasal treatment with Org39141 was well tolerated, and no serious or severe AE were reported. (PMID:16960935)
• High YKL40 is associated with high-grade gliomas (PMID:17020973)
• CHI3L1 as a potential schizophrenia-susceptibility gene and suggest that the genes involved in the biological response to adverse environmental conditions are likely to play roles in the predisposition to schizophrenia. (PMID:17160890)
• YKL-40 may be used as a sarcoidosis disease marker, but it is unsuitable as a marker to predict the course of the disease. (PMID:17236752)
• conformational comparison of MGP40 and HUMGP39 (PMID:17543889)
• YKL-40 has a role in success of hormonal treatment for metastatic prostate cancer (PMID:17545529)
• Data suggest that measuring YKL-40 in nipple aspirate fluid may improve the identification of women at increased breast cancer risk. (PMID:17565739)
• A candidate autoantigen in rheumatoid arthritis found in synovial fluid cells. (PMID:17599744)
• YKL-40 release by intervertebral disc culture may better clarify its role in the pathophysiology of discal degeneration and inflammation and its relationships with COX-2 and NO in disc tissue culture. (PMID:17631744)
• YKL-40 is associated with cell proliferation, differentiation, and tissue morphogenesis during development of the human musculoskeletal system (PMID:17712177)
• High serum levels of YKL-40 is associated with squamous cell carcinoma of the head and neck (PMID:17957792)
• concentration in cord serum significantly higher in pre-eclamptic pregnancies but no significant difference in maternal serum levels between the case and control groups (PMID:18054022)
• High levels of CHI3L1 is associated with glioblastoma (PMID:18092325)
• YKL-40 protein may not have a role in progression of primary breast cancer (PMID:18157633)
• potential role for YKL-40 in myeloma-related bone disease must be considered (PMID:18182077)
• High serum YKL-40 levels in patients with primary prostate cancer indicate that YKL-40 may have a function in the progression of malignant diseases. (PMID:18190830)
• YKL-40 does not seem to have a role in liver fibrosis in children with chronic hepatitis B (PMID:18217402)
• We show that elevated YKL-40 levels are not correlated with the severity of subarachnoid haemorrhage and cannot be used as a serological marker of inflammation in patients with an aneurysm rupture. (PMID:18280741)
• We identified significant association with the same risk allele at the promoter single nucleotide polymorphism (SNP) associated in the original study (rs10399805; p = .018) and with another SNP at intron 7 of CHI3L1 (rs2275351; p = .008). (PMID:18281018)
• CHI3L1 is a susceptibility gene for asthma, bronchial hyperresponsiveness, and reduced lung function, and elevated circulating YKL-40 levels are a biomarker for asthma and decline in lung function. (PMID:18403759)
• serum concentrations of YKL-40 (chitinase 3-like 1) are greatly increased in AMI patients with and without thrombolytic therapy (PMID:18480670)
• involved in the enhancement of chitin binding protein-expressing bacterial adhesion to colonic epithelial cells (PMID:18490894)
• YKL-40 protein expression was redistributed in carcinoma versus normal glandular tissue of the breast. (PMID:18570155)

Cross-species orthologs

43 orthologs

Organism	Symbol	Gene ID
mus_musculus	Chi3l1	ENSMUSG00000064246
rattus_norvegicus	Chi3l1	ENSRNOG00000053272
drosophila_melanogaster	Idgf6	FBGN0013763
drosophila_melanogaster	Idgf3	FBGN0020414
drosophila_melanogaster	Idgf2	FBGN0020415
drosophila_melanogaster	Idgf1	FBGN0020416
drosophila_melanogaster	Cht4	FBGN0022700
drosophila_melanogaster	Idgf4	FBGN0026415
drosophila_melanogaster	Cht8	FBGN0034580
drosophila_melanogaster	Cht9	FBGN0034582
drosophila_melanogaster	Cht7	FBGN0035398
drosophila_melanogaster	Cht12	FBGN0050293
drosophila_melanogaster	Cda4	FBGN0052499
drosophila_melanogaster	Idgf5	FBGN0064237
drosophila_melanogaster	Cht10	FBGN0250907
caenorhabditis_elegans		WBGENE00000503
caenorhabditis_elegans		WBGENE00007465
caenorhabditis_elegans		WBGENE00007466
caenorhabditis_elegans		WBGENE00007467
caenorhabditis_elegans		WBGENE00007469
caenorhabditis_elegans		WBGENE00007470
caenorhabditis_elegans		WBGENE00007471
caenorhabditis_elegans		WBGENE00007472
caenorhabditis_elegans		WBGENE00007473
caenorhabditis_elegans		WBGENE00010799
caenorhabditis_elegans		WBGENE00010945
caenorhabditis_elegans		WBGENE00011157
caenorhabditis_elegans		WBGENE00011158
caenorhabditis_elegans		WBGENE00011159
caenorhabditis_elegans		WBGENE00011161
caenorhabditis_elegans		WBGENE00011162
caenorhabditis_elegans		WBGENE00011164
caenorhabditis_elegans		WBGENE00011166
caenorhabditis_elegans		WBGENE00011167
caenorhabditis_elegans		WBGENE00011170
caenorhabditis_elegans		WBGENE00011846
caenorhabditis_elegans		WBGENE00014162
caenorhabditis_elegans		WBGENE00016665
caenorhabditis_elegans		WBGENE00017233
caenorhabditis_elegans		WBGENE00020141
caenorhabditis_elegans		WBGENE00020407
caenorhabditis_elegans		WBGENE00044546
caenorhabditis_elegans		WBGENE00044807

Paralogs (6): CHI3L2 (ENSG00000064886), OVGP1 (ENSG00000085465), CTBS (ENSG00000117151), CHIT1 (ENSG00000133063), CHIA (ENSG00000134216), CHID1 (ENSG00000177830)

Protein

Protein identifiers

Chitinase-3-like protein 1 — P36222 (reviewed: P36222)

Alternative names: 39 kDa synovial protein, Cartilage glycoprotein 39, YKL-40

All UniProt accessions (2): P36222, H0Y3U8

UniProt curated annotations — full annotation on UniProt →

Function. Carbohydrate-binding lectin with a preference for chitin. Has no chitinase activity. May play a role in tissue remodeling and in the capacity of cells to respond to and cope with changes in their environment. Plays a role in T-helper cell type 2 (Th2) inflammatory response and IL-13-induced inflammation, regulating allergen sensitization, inflammatory cell apoptosis, dendritic cell accumulation and M2 macrophage differentiation. Facilitates invasion of pathogenic enteric bacteria into colonic mucosa and lymphoid organs. Mediates activation of AKT1 signaling pathway and subsequent IL8 production in colonic epithelial cells. Regulates antibacterial responses in lung by contributing to macrophage bacterial killing, controlling bacterial dissemination and augmenting host tolerance. Also regulates hyperoxia-induced injury, inflammation and epithelial apoptosis in lung.

Subunit / interactions. Monomer.

Subcellular location. Secreted. Extracellular space. Cytoplasm. Perinuclear region. Endoplasmic reticulum.

Tissue specificity. Present in activated macrophages, articular chondrocytes, synovial cells as well as in liver. Very low or undetectable expression in non-inflammatory colon. Undetectable in muscle tissues, lung, pancreas, mononuclear cells, or fibroblasts.

Post-translational modifications. Glycosylated.

Disease relevance. Asthma-related traits 7 (ASRT7) [MIM:611960] Asthma-related traits include clinical symptoms of asthma, such as coughing, wheezing, dyspnea, bronchial hyperresponsiveness as assessed by methacholine challenge test, serum IgE levels, atopy and atopic dermatitis. Disease susceptibility is associated with variants affecting the gene represented in this entry. Schizophrenia (SCZD) [MIM:181500] A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Induction. Up-regulated in colon under several inflammatory conditions. Down-regulated by hyperoxia in bronchial epithelial cells.

Similarity. Belongs to the glycosyl hydrolase 18 family.

RefSeq proteins (1): NP_001267* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001223	Glyco_hydro18_cat	Domain
IPR011583	Chitinase_II/V-like_cat	Domain
IPR017853	GH_hydrolase_sf	Homologous_superfamily
IPR029070	Chitinase_insertion_sf	Homologous_superfamily
IPR050314	Glycosyl_Hydrlase_18	Family

Pfam: PF00704

UniProt features (58 total): helix 19, strand 18, turn 6, binding site 6, disulfide bond 2, sequence variant 2, signal peptide 1, chain 1, glycosylation site 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
8R4X	X-RAY DIFFRACTION	1.54
1HJX	X-RAY DIFFRACTION	1.85
1NWU	X-RAY DIFFRACTION	2.2
8R41	X-RAY DIFFRACTION	2.25
1HJW	X-RAY DIFFRACTION	2.3
8ZAZ	X-RAY DIFFRACTION	2.31
8R42	X-RAY DIFFRACTION	2.32
1NWT	X-RAY DIFFRACTION	2.5
1NWR	X-RAY DIFFRACTION	2.7
1NWS	X-RAY DIFFRACTION	2.7
7CJ2	X-RAY DIFFRACTION	2.7
1HJV	X-RAY DIFFRACTION	2.75
8DF1	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P36222-F1	95.08	0.92

Antibody-complex structures (SAbDab): 2 — 7CJ2, 8DF1

Functional residue map

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

Ligand- & substrate-binding residues (6): 70–71; 97–100; 141; 204–207; 263; 352

Disulfide bonds (2): 26–51, 300–364

Glycosylation sites (1): 60

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 287 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, REACTOME_INNATE_IMMUNE_SYSTEM, MCLACHLAN_DENTAL_CARIES_UP, GOBP_CARTILAGE_DEVELOPMENT, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOBP_RESPONSE_TO_PEPTIDE, GOCC_SECRETORY_GRANULE, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, YANG_BREAST_CANCER_ESR1_LASER_DN, GOBP_ACTIVATION_OF_NF_KAPPAB_INDUCING_KINASE_ACTIVITY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS

GO Biological Process (17): carbohydrate metabolic process (GO:0005975), chitin catabolic process (GO:0006032), apoptotic process (GO:0006915), inflammatory response (GO:0006954), activation of NF-kappaB-inducing kinase activity (GO:0007250), response to mechanical stimulus (GO:0009612), positive regulation of peptidyl-threonine phosphorylation (GO:0010800), lung development (GO:0030324), positive regulation of interleukin-8 production (GO:0032757), response to tumor necrosis factor (GO:0034612), positive regulation of angiogenesis (GO:0045766), cartilage development (GO:0051216), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of ERK1 and ERK2 cascade (GO:0070374), response to interleukin-1 (GO:0070555), response to interleukin-6 (GO:0070741), cellular response to tumor necrosis factor (GO:0071356)

GO Molecular Function (4): extracellular matrix structural constituent (GO:0005201), chitin binding (GO:0008061), carbohydrate binding (GO:0030246), protein binding (GO:0005515)

GO Cellular Component (8): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), extracellular matrix (GO:0031012), specific granule lumen (GO:0035580), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to cytokine	3
cellular anatomical structure	3
animal organ development	2
binding	2
cytoplasm	2
primary metabolic process	1
aminoglycan catabolic process	1
chitin metabolic process	1
glucosamine-containing compound catabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
defense response	1
activation of protein kinase activity	1
non-canonical NF-kappaB signal transduction	1
response to external stimulus	1
response to abiotic stimulus	1
positive regulation of protein phosphorylation	1
regulation of peptidyl-threonine phosphorylation	1
peptidyl-threonine phosphorylation	1
respiratory tube development	1
respiratory system development	1
positive regulation of cytokine production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
angiogenesis	1
regulation of angiogenesis	1
positive regulation of vasculature development	1
skeletal system development	1
connective tissue development	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
response to tumor necrosis factor	1
cellular response to cytokine stimulus	1
structural molecule activity	1
extracellular matrix	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

59 interactions, top by confidence:

A	B	Type	Score
CHI3L1	IL13RA2	psi-mi:“MI:0915”(physical association)	0.800
CHI3L1	IL13RA2	psi-mi:“MI:0407”(direct interaction)	0.800
IL13RA2	CHI3L1	psi-mi:“MI:0915”(physical association)	0.800
BABAM2	SHMT2	psi-mi:“MI:0914”(association)	0.640
DDHD2	CHI3L1	psi-mi:“MI:0914”(association)	0.530
LGALS3	CHI3L1	psi-mi:“MI:0915”(physical association)	0.520
CHI3L1	AKT1	psi-mi:“MI:2364”(proximity)	0.470
CHI3L1	BRAF	psi-mi:“MI:2364”(proximity)	0.470
CHI3L1	AKT1	psi-mi:“MI:0915”(physical association)	0.470
BRAF	CHI3L1	psi-mi:“MI:0915”(physical association)	0.470
CD55	CHI3L1	psi-mi:“MI:0915”(physical association)	0.400
CHI3L1	UBLCP1	psi-mi:“MI:0915”(physical association)	0.400
Il13ra2	CHI3L1	psi-mi:“MI:0914”(association)	0.350
CHI3L1	HSPA8	psi-mi:“MI:0914”(association)	0.350
MTRF1L	CHI3L1	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
IDH3B	DCX	psi-mi:“MI:0914”(association)	0.350
BABAM2	DCX	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): CHI3L1 (Affinity Capture-MS), CHI3L1 (Affinity Capture-MS), CHI3L1 (Affinity Capture-MS), CHI3L1 (Affinity Capture-MS), CHI3L1 (Affinity Capture-MS), CHI3L1 (Affinity Capture-MS), CHI3L1 (Affinity Capture-MS), CALR (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), CHI3L1 (Co-localization), CHI3L1 (Affinity Capture-RNA), CHI3L1 (Affinity Capture-MS), UBLCP1 (Affinity Capture-MS), CHI3L1 (Affinity Capture-MS), CHI3L1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0W0FPC8, A1CRV0, A1D4Q5, A2RAR6, A6N6J0, B0XN12, B3A0S5, C5P230, D4AJL7, E9ERT9, E9QRF2, G0RA32, G4MPQ7, G4NI45, G5EAZ3, I1S3C6, M4MEY9, O14456, O60206, O93983, P0CB51, P23360, P29060, P29717, P32470, P36222, P46239, P48827, P79046, P83692, Q0CR35, Q0CTQ7, Q12713, Q12725, Q13231, Q1E3R8, Q29411, Q2PGV8, Q4P902, Q4WK60

Diamond homologs: A0A072UR65, A0A072VEP0, A0A1B1J8Z2, O81862, P36222, P36718, Q12889, Q28990, Q29411, Q5RBP6, Q60557, Q61362, Q9WTV1, U5N4E3, A6N6J0, E9ERT9, O35744, P29030, P36362, P48827, Q13231, Q15782, Q28042, Q28542, Q62010, Q6RY07, Q91XA9, Q91Z98, Q95M17, Q9BZP6, Q9W092, Q9W5U2, O14456, P20533, P30922, P36909, Q6TMG6, Q8SPQ0, A0A0A2JVV3, C5P230

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
STAT6	“up-regulates quantity by expression”	CHI3L1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 39 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of ERK1 and ERK2 cascade	5	11.2×	8e-03
negative regulation of apoptotic process	8	7.3×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	84
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1716 predictions. Top by Δscore:

Variant	Effect	Δscore
1:203179756:CCTA:C	donor_loss	1.0000
1:203179757:CTACC:C	donor_loss	1.0000
1:203179758:TA:T	donor_loss	1.0000
1:203179760:C:CG	donor_loss	1.0000
1:203179760:CCTTG:C	donor_gain	1.0000
1:203179873:CAGAT:C	acceptor_gain	1.0000
1:203179876:ATC:A	acceptor_loss	1.0000
1:203179877:TCTG:T	acceptor_loss	1.0000
1:203179878:C:CC	acceptor_gain	1.0000
1:203179883:C:CT	acceptor_gain	1.0000
1:203179884:A:T	acceptor_gain	1.0000
1:203181160:A:AC	donor_gain	1.0000
1:203181161:C:CC	donor_gain	1.0000
1:203181161:CA:C	donor_gain	1.0000
1:203181161:CAGTG:C	donor_gain	1.0000
1:203182727:TCAC:T	donor_loss	1.0000
1:203182728:CA:C	donor_loss	1.0000
1:203182729:A:AC	donor_gain	1.0000
1:203182729:ACTGG:A	donor_loss	1.0000
1:203182730:C:CT	donor_gain	1.0000
1:203182730:CTG:C	donor_gain	1.0000
1:203182730:CTGGG:C	donor_gain	1.0000
1:203182754:G:C	donor_gain	1.0000
1:203182851:TCCTA:T	acceptor_loss	1.0000
1:203182853:CT:C	acceptor_loss	1.0000
1:203179464:T:TA	donor_gain	0.9900
1:203179759:A:AC	donor_gain	0.9900
1:203179760:C:CC	donor_gain	0.9900
1:203179777:T:A	donor_gain	0.9900
1:203179875:GAT:G	acceptor_gain	0.9900

AlphaMissense

2527 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:203181213:A:C	S220R	0.988
1:203181213:A:T	S220R	0.988
1:203181215:T:G	S220R	0.988
1:203179761:C:A	K337N	0.985
1:203179761:C:G	K337N	0.985
1:203179799:A:G	W325R	0.984
1:203179799:A:T	W325R	0.984
1:203179797:C:A	W325C	0.982
1:203179797:C:G	W325C	0.982
1:203182793:G:C	S175R	0.981
1:203182793:G:T	S175R	0.981
1:203182795:T:G	S175R	0.981
1:203179817:C:G	A319P	0.977
1:203183710:A:C	F132L	0.977
1:203183710:A:T	F132L	0.977
1:203183712:A:G	F132L	0.977
1:203180569:G:C	F265L	0.976
1:203180569:G:T	F265L	0.976
1:203180571:A:G	F265L	0.976
1:203185270:G:C	S57R	0.975
1:203185270:G:T	S57R	0.975
1:203185272:T:G	S57R	0.975
1:203183691:A:G	W139R	0.973
1:203183691:A:T	W139R	0.973
1:203183711:A:G	F132S	0.973
1:203185267:A:C	F58L	0.973
1:203185267:A:T	F58L	0.973
1:203185269:A:G	F58L	0.973
1:203180580:C:A	G262W	0.972
1:203185286:G:A	T52I	0.970

dbSNP variants (sampled 300 via entrez): RS1000050282 (1:203182124 C>T), RS1000445136 (1:203186388 C>A,T), RS1000652636 (1:203179910 G>A), RS1000654536 (1:203180946 G>A), RS1001140950 (1:203184192 C>T), RS1001444842 (1:203183826 A>C,T), RS1001997339 (1:203186021 G>A), RS1002016645 (1:203180410 C>A,T), RS1002039786 (1:203180114 G>A,T), RS1002456083 (1:203186254 C>T), RS1003019596 (1:203179393 C>A,T), RS1003407946 (1:203184781 G>A,C), RS1003711522 (1:203182647 C>T), RS1004104290 (1:203188186 C>T), RS1004194161 (1:203180835 C>A)

Disease associations

OMIM: gene MIM:601525 | disease phenotypes: MIM:181500, MIM:611960

GenCC curated gene-disease

Disease	Classification	Inheritance
schizophrenia	No Known Disease Relationship	Unknown

Mondo (2): schizophrenia (MONDO:0005090), asthma-related traits, susceptibility to, 7 (MONDO:0012771)

Orphanet (1): NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000738	Hallucinations
HP:0000746	Delusion
HP:0002353	EEG abnormality
HP:0007086	Social and occupational deterioration
HP:0100753	Schizophrenia
HP:0410291	Negativism

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000177_1	YKL-40 levels	1.000000e-13
GCST002595_27	Clozapine-induced agranulocytosis	9.000000e-06
GCST009391_490	Metabolite levels	2.000000e-06
GCST009391_614	Metabolite levels	1.000000e-06
GCST009731_39	Blood protein levels in cardiovascular risk	2.000000e-236
GCST009798_35	Asthma	8.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004869	YKL40 measurement
EFO:0005001	phenylalanine measurement
EFO:0009793	isoleucine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724768 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — Chitinase-like proteins

Binding affinities (BindingDB)

79 measured of 172 human assays (172 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[(2R,5S)-5-[(4-chlorophenyl)methyl]-4-(1-pyridin-2-ylpiperidin-4-yl)morpholin-2-yl]methyl 3-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoate	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-4-[1-(5-chloro-2-pyridinyl)piperidin-4-yl]-2-methylmorpholine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-4-[1-(3-fluoro-2-pyridinyl)piperidin-4-yl]-2-methylmorpholine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-methyl-4-(1-pyridin-2-ylpiperidin-4-yl)morpholine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
2-[4-[(2S,5S)-5-[(4-chlorophenyl)methyl]-2-methylmorpholin-4-yl]piperidin-1-yl]pyridine-3-carbonitrile	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-4-[1-(4-methoxy-2-pyridinyl)piperidin-4-yl]-2-methylmorpholine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-4-[1-(4-chloro-2-pyridinyl)-2-methylpiperidin-4-yl]-2-methylmorpholine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-methyl-4-[1-(4-methylpyrimidin-2-yl)piperidin-4-yl]morpholine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(3S,7R,8aS)-3-[(4-chlorophenyl)methyl]-2-(1-pyrimidin-2-ylpiperidin-4-yl)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-7-ol	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(3S,7R,8aS)-3-[(4-chlorophenyl)methyl]-2-[1-(4-methylpyrimidin-2-yl)piperidin-4-yl]-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-7-ol	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(3S,7S,8aS)-3-[(4-chlorophenyl)methyl]-2-(1-pyrimidin-2-ylpiperidin-4-yl)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-7-ol	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(3S,7S,8aS)-3-[(4-chlorophenyl)methyl]-2-[1-(4-methylpyrimidin-2-yl)piperidin-4-yl]-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-7-ol	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
2-[4-[(2S,5S)-5-[(4-chlorophenyl)methyl]-2-methylmorpholin-4-yl]piperidin-1-yl]-4-methylpyridine-3-carbonitrile	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,4S)-2-[(4-chlorophenyl)methyl]-1-(1-pyridin-2-ylpiperidin-4-yl)piperidin-4-ol	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-1-methyl-2-(2-methylpropyl)-4-(1-pyridin-2-ylpiperidin-4-yl)piperazine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(3S,9aS)-3-[(4-chlorophenyl)methyl]-2-(1-pyridin-2-ylpiperidin-4-yl)-1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-2-[(4-chlorophenyl)methyl]-1-[(3R)-3-methoxy-1-pyridin-2-ylpiperidin-4-yl]-4,5-dimethylpiperazine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S)-2-[(4-chlorophenyl)methyl]-4-methyl-1-(1-pyridin-2-ylpiperidin-4-yl)piperazine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-cyclopentyl-1-methyl-4-(1-pyridin-2-ylpiperidin-4-yl)piperazine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-cyclopropyl-1-methyl-4-(1-pyridin-2-ylpiperidin-4-yl)piperazine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-4-[1-(4-chloro-2-pyridinyl)piperidin-4-yl]-2-propan-2-ylmorpholine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
N-[[(2S)-5-[(4-chlorophenyl)methyl]-4-(1-pyrimidin-2-ylpiperidin-4-yl)morpholin-2-yl]methyl]acetamide	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(3S,5S)-5-[(4-chlorophenyl)methyl]-1-(1-pyridin-2-ylpiperidin-4-yl)pyrrolidin-3-ol	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-methyl-1-(2-methylpropyl)-4-(1-pyridin-2-ylpiperidin-4-yl)piperazine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-propan-2-yl-4-(1-pyridin-2-ylpiperidin-4-yl)morpholine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(3S)-3-[(4-chlorophenyl)methyl]-4-(1-pyridin-2-ylpiperidin-4-yl)morpholine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2R)-1-[(2S,5S)-5-[(4-chlorophenyl)methyl]-2-methyl-4-(1-pyridin-2-ylpiperidin-4-yl)piperazin-1-yl]propan-2-ol	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
2-[(2S,5S)-5-[(4-chlorophenyl)methyl]-2-ethyl-4-(1-pyridin-2-ylpiperidin-4-yl)piperazin-1-yl]-N-cyclopropylacetamide	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-1-[(2R)-2-methoxypropyl]-2-methyl-4-(1-pyridin-2-ylpiperidin-4-yl)piperazine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
2-[4-[(2S,4S)-2-[(4-chlorophenyl)methyl]-4-methoxypiperidin-1-yl]piperidin-1-yl]pyridine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-4-[1-(3-fluoro-4-methyl-2-pyridinyl)piperidin-4-yl]-2-methylmorpholine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-4-[1-(4-bromo-2-pyridinyl)piperidin-4-yl]-5-[(4-chlorophenyl)methyl]-2-methylmorpholine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-methyl-4-(1-pyrimidin-5-ylpiperidin-4-yl)morpholine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-methyl-4-(1-pyrimidin-2-ylpiperidin-4-yl)morpholine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
[(2R)-5-[(4-chlorophenyl)methyl]-4-(1-pyridin-2-ylpiperidin-4-yl)morpholin-2-yl]methyl acetate	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2R)-5-[(4-chlorophenyl)methyl]-2-(methoxymethyl)-4-(1-pyridin-2-ylpiperidin-4-yl)morpholine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2R)-5-[(4-chlorophenyl)methyl]-2-(propan-2-yloxymethyl)-4-(1-pyridin-2-ylpiperidin-4-yl)morpholine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
[(2R)-5-[(4-chlorophenyl)methyl]-4-(1-pyridin-2-ylpiperidin-4-yl)morpholin-2-yl]methyl N-cyclopropylcarbamate	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(7S)-7-[(4-chlorophenyl)methyl]-5-methyl-8-(1-pyridin-2-ylpiperidin-4-yl)-5,8-diazaspiro[3.5]nonane	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2R,5S)-5-[(4-chlorophenyl)methyl]-2-(2-methoxypropan-2-yl)-4-(1-pyridin-2-ylpiperidin-4-yl)morpholine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2R,5S)-5-[(4-chlorophenyl)methyl]-N-methyl-4-(1-pyridin-2-ylpiperidin-4-yl)morpholine-2-carboxamide	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-methyl-4-(4-pyridin-2-ylphenyl)morpholine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(3S,8aS)-3-[(4-chlorophenyl)methyl]-2-[1-(4-chloro-2-pyridinyl)piperidin-4-yl]-7,7-difluoro-1,3,4,6,8,8a-hexahydropyrrolo[1,2-a]pyrazine	IC50	550 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-4-[1-(5-fluoro-2-pyridinyl)piperidin-4-yl]-2-methylmorpholine	IC50	5500 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-4-[1-(6-fluoro-2-pyridinyl)piperidin-4-yl]-2-methylmorpholine	IC50	5500 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-methyl-4-(1-pyrazin-2-ylpiperidin-4-yl)morpholine	IC50	5500 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-4-[1-(6-chloro-2-pyridinyl)piperidin-4-yl]-2-methylmorpholine	IC50	5500 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-4-[1-(2-fluoro-4-pyridinyl)piperidin-4-yl]-2-methylmorpholine	IC50	5500 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-methyl-4-[1-[4-(trifluoromethyl)-2-pyridinyl]piperidin-4-yl]morpholine	IC50	5500 nM	US-12325701: YKL-40 inhibitors and their therapeutic
(2S,5S)-5-[(4-chlorophenyl)methyl]-4-[1-(3-chloro-2-pyridinyl)piperidin-4-yl]-2-methylmorpholine	IC50	5500 nM	US-12325701: YKL-40 inhibitors and their therapeutic

ChEMBL bioactivities

32 potent at pChembl≥5 of 36 total, top 32 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.60	IC50	25	nM	CHEMBL5568901
7.58	IC50	26	nM	CHEMBL5573764
7.52	IC50	30	nM	CHEMBL5542422
7.50	IC50	32	nM	CHEMBL5572500
7.47	IC50	34	nM	CHEMBL6067702
7.44	IC50	36	nM	CHEMBL5574339
7.43	IC50	37	nM	CHEMBL5542749
7.42	IC50	38	nM	CHEMBL5568720
7.32	IC50	48	nM	CHEMBL5595737
7.30	IC50	50	nM	CHEMBL5542749
7.23	Kd	59	nM	CHEMBL5563255
7.11	IC50	78	nM	CHEMBL5592069
7.09	IC50	82	nM	CHEMBL5565054
6.96	IC50	111	nM	CHEMBL5573764
6.96	IC50	109	nM	CHEMBL5568901
6.93	IC50	118	nM	CHEMBL5592069
6.89	IC50	130	nM	CHEMBL5592069
6.88	IC50	131	nM	CHEMBL5572262
6.84	IC50	144	nM	CHEMBL5562544
6.82	IC50	150	nM	CHEMBL5572352
6.75	IC50	180	nM	CHEMBL5570010
6.72	IC50	190	nM	CHEMBL5563081
6.72	IC50	191	nM	CHEMBL5573117
6.72	IC50	190	nM	CHEMBL5572352
6.71	IC50	194	nM	CHEMBL6067702
6.69	IC50	203	nM	CHEMBL5569707
6.43	IC50	375	nM	CHEMBL5572500
6.36	IC50	440	nM	CHEMBL5570939
6.31	IC50	486	nM	CHEMBL5562985
6.21	IC50	611	nM	CHEMBL5556012
5.29	IC50	5100	nM	CHEMBL5575916
5.09	Kd	8200	nM	CHEMBL5563081

PubChem BioAssay actives

32 with measured affinity, of 48 total; 23 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
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-cyclopropyl-1-methyl-4-(1-pyridin-2-ylpiperidin-4-yl)piperazine	2090850: Displacement of biotinylated HSIII from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells by competitive AlphaScreen assay	ic50	0.0250	uM
(2S,5S)-5-[(4-chlorophenyl)methyl]-1-methyl-2-(2-methylpropyl)-4-(1-pyridin-2-ylpiperidin-4-yl)piperazine	2090850: Displacement of biotinylated HSIII from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells by competitive AlphaScreen assay	ic50	0.0260	uM
2-[(2R,5S)-5-[(4-chlorophenyl)methyl]-4-(1-pyridin-2-ylpiperidin-4-yl)morpholin-2-yl]propan-2-ol	2090833: Displacement of biotinylated ((2R,5S)-5-(4-chlorobenzyl)-4-(1-(pyridin-2-yl)piperidin-4-yl)morpholin-2-yl)methyl 41-oxo-45-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol4-yl)-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azapentatetracontanoate from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells incubated for 1 hr by competitive AlphaScreen assay	ic50	0.0300	uM
(2R,5S)-5-[(4-chlorophenyl)methyl]-2-(propan-2-yloxymethyl)-4-(1-pyridin-2-ylpiperidin-4-yl)morpholine	2090850: Displacement of biotinylated HSIII from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells by competitive AlphaScreen assay	ic50	0.0320	uM
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-cyclopentyl-1-methyl-4-(1-pyridin-2-ylpiperidin-4-yl)piperazine	2090850: Displacement of biotinylated HSIII from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells by competitive AlphaScreen assay	ic50	0.0340	uM
(2S,5S)-5-[(4-chlorophenyl)methyl]-4-[1-(4-fluoro-2-pyridinyl)piperidin-4-yl]-2-methylmorpholine	2090833: Displacement of biotinylated ((2R,5S)-5-(4-chlorobenzyl)-4-(1-(pyridin-2-yl)piperidin-4-yl)morpholin-2-yl)methyl 41-oxo-45-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol4-yl)-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azapentatetracontanoate from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells incubated for 1 hr by competitive AlphaScreen assay	ic50	0.0360	uM
(2S,5S)-5-[(4-chlorophenyl)methyl]-4-[1-(4-chloro-2-pyridinyl)piperidin-4-yl]-2-methylmorpholine	2090850: Displacement of biotinylated HSIII from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells by competitive AlphaScreen assay	ic50	0.0370	uM
(3S,7S,8aS)-3-[(4-chlorophenyl)methyl]-2-(1-pyridin-2-ylpiperidin-4-yl)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-7-ol	2090833: Displacement of biotinylated ((2R,5S)-5-(4-chlorobenzyl)-4-(1-(pyridin-2-yl)piperidin-4-yl)morpholin-2-yl)methyl 41-oxo-45-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol4-yl)-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azapentatetracontanoate from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells incubated for 1 hr by competitive AlphaScreen assay	ic50	0.0380	uM
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-methyl-4-[1-(4-methyl-2-pyridinyl)piperidin-4-yl]morpholine	2090833: Displacement of biotinylated ((2R,5S)-5-(4-chlorobenzyl)-4-(1-(pyridin-2-yl)piperidin-4-yl)morpholin-2-yl)methyl 41-oxo-45-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol4-yl)-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azapentatetracontanoate from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells incubated for 1 hr by competitive AlphaScreen assay	ic50	0.0480	uM
[(2R,5S)-5-[(4-chlorophenyl)methyl]-4-(1-pyridin-2-ylpiperidin-4-yl)morpholin-2-yl]methyl 3-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoate	2090852: Binding affinity to human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells assessed as dissociation constant by bio-layer interferometry streptavidin sensor based assay	kd	0.0590	uM
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-methyl-4-(1-pyridin-2-ylpiperidin-4-yl)morpholine	2090850: Displacement of biotinylated HSIII from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells by competitive AlphaScreen assay	ic50	0.0780	uM
(2R,5S)-5-[(4-chlorophenyl)methyl]-4-[1-(4-chloro-2-pyridinyl)piperidin-4-yl]-2-(methylsulfonylmethyl)morpholine	2090833: Displacement of biotinylated ((2R,5S)-5-(4-chlorobenzyl)-4-(1-(pyridin-2-yl)piperidin-4-yl)morpholin-2-yl)methyl 41-oxo-45-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol4-yl)-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azapentatetracontanoate from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells incubated for 1 hr by competitive AlphaScreen assay	ic50	0.0820	uM
(2S,5S)-5-[(4-chlorophenyl)methyl]-4-[1-(3-fluoro-2-pyridinyl)piperidin-4-yl]-2-methylmorpholine	2090833: Displacement of biotinylated ((2R,5S)-5-(4-chlorobenzyl)-4-(1-(pyridin-2-yl)piperidin-4-yl)morpholin-2-yl)methyl 41-oxo-45-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol4-yl)-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azapentatetracontanoate from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells incubated for 1 hr by competitive AlphaScreen assay	ic50	0.1310	uM
[(2R,5S)-5-[(4-chlorophenyl)methyl]-4-(1-pyridin-2-ylpiperidin-4-yl)morpholin-2-yl]methanol	2090833: Displacement of biotinylated ((2R,5S)-5-(4-chlorobenzyl)-4-(1-(pyridin-2-yl)piperidin-4-yl)morpholin-2-yl)methyl 41-oxo-45-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol4-yl)-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azapentatetracontanoate from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells incubated for 1 hr by competitive AlphaScreen assay	ic50	0.1440	uM
(2S,5S)-5-[(4-chlorophenyl)methyl]-1,2-dimethyl-4-(1-pyridin-2-ylpiperidin-4-yl)piperazine	2090833: Displacement of biotinylated ((2R,5S)-5-(4-chlorobenzyl)-4-(1-(pyridin-2-yl)piperidin-4-yl)morpholin-2-yl)methyl 41-oxo-45-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol4-yl)-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azapentatetracontanoate from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells incubated for 1 hr by competitive AlphaScreen assay	ic50	0.1500	uM
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-methyl-4-[1-(1,3-thiazol-2-yl)piperidin-4-yl]morpholine	2090833: Displacement of biotinylated ((2R,5S)-5-(4-chlorobenzyl)-4-(1-(pyridin-2-yl)piperidin-4-yl)morpholin-2-yl)methyl 41-oxo-45-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol4-yl)-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azapentatetracontanoate from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells incubated for 1 hr by competitive AlphaScreen assay	ic50	0.1800	uM
N-[2-(4-chlorophenyl)ethyl]-N-methyl-4-(3-methyl-1,2-oxazol-5-yl)cyclohexan-1-amine	2090833: Displacement of biotinylated ((2R,5S)-5-(4-chlorobenzyl)-4-(1-(pyridin-2-yl)piperidin-4-yl)morpholin-2-yl)methyl 41-oxo-45-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol4-yl)-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azapentatetracontanoate from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells incubated for 1 hr by competitive AlphaScreen assay	ic50	0.1900	uM
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-propan-2-yl-4-(1-pyridin-2-ylpiperidin-4-yl)morpholine	2090833: Displacement of biotinylated ((2R,5S)-5-(4-chlorobenzyl)-4-(1-(pyridin-2-yl)piperidin-4-yl)morpholin-2-yl)methyl 41-oxo-45-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol4-yl)-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azapentatetracontanoate from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells incubated for 1 hr by competitive AlphaScreen assay	ic50	0.1910	uM
(2R,5S)-5-[(4-chlorophenyl)methyl]-2-(methoxymethyl)-4-(1-pyridin-2-ylpiperidin-4-yl)morpholine	2090833: Displacement of biotinylated ((2R,5S)-5-(4-chlorobenzyl)-4-(1-(pyridin-2-yl)piperidin-4-yl)morpholin-2-yl)methyl 41-oxo-45-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol4-yl)-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azapentatetracontanoate from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells incubated for 1 hr by competitive AlphaScreen assay	ic50	0.2030	uM
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-methyl-4-(1-pyrimidin-5-ylpiperidin-4-yl)morpholine	2090833: Displacement of biotinylated ((2R,5S)-5-(4-chlorobenzyl)-4-(1-(pyridin-2-yl)piperidin-4-yl)morpholin-2-yl)methyl 41-oxo-45-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol4-yl)-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azapentatetracontanoate from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells incubated for 1 hr by competitive AlphaScreen assay	ic50	0.4400	uM
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-methyl-1-(2-methylpropyl)-4-(1-pyridin-2-ylpiperidin-4-yl)piperazine	2090833: Displacement of biotinylated ((2R,5S)-5-(4-chlorobenzyl)-4-(1-(pyridin-2-yl)piperidin-4-yl)morpholin-2-yl)methyl 41-oxo-45-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol4-yl)-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azapentatetracontanoate from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells incubated for 1 hr by competitive AlphaScreen assay	ic50	0.4860	uM
(2S,5S)-5-[(4-chlorophenyl)methyl]-2-methyl-4-(1-pyrimidin-2-ylpiperidin-4-yl)morpholine	2090833: Displacement of biotinylated ((2R,5S)-5-(4-chlorobenzyl)-4-(1-(pyridin-2-yl)piperidin-4-yl)morpholin-2-yl)methyl 41-oxo-45-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol4-yl)-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azapentatetracontanoate from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells incubated for 1 hr by competitive AlphaScreen assay	ic50	0.6110	uM
(2S,5S)-5-[(4-chlorophenyl)methyl]-4-[1-(6-fluoro-2-pyridinyl)piperidin-4-yl]-2-methylmorpholine	2090833: Displacement of biotinylated ((2R,5S)-5-(4-chlorobenzyl)-4-(1-(pyridin-2-yl)piperidin-4-yl)morpholin-2-yl)methyl 41-oxo-45-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol4-yl)-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azapentatetracontanoate from human His-tagged CHI3L1 (1 to 383 residues) expressed in HEK293F cells incubated for 1 hr by competitive AlphaScreen assay	ic50	5.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression, increases methylation	8
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	7
Cyclosporine	decreases expression, affects cotreatment	4
bisphenol A	decreases expression, affects cotreatment, increases methylation, increases expression	3
Arsenic Trioxide	decreases expression, increases expression, affects cotreatment	3
Dexamethasone	decreases expression, affects cotreatment	3
Doxorubicin	decreases response to substance, decreases expression, increases expression	3
Tretinoin	affects cotreatment, decreases expression, increases expression	3
trichostatin A	decreases expression	2
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Air Pollutants	increases abundance, increases expression, affects cotreatment	2
Cisplatin	decreases response to substance, increases expression	2
Diethylhexyl Phthalate	decreases expression, decreases reaction	2
Estradiol	affects cotreatment, decreases expression	2
Ozone	increases abundance, affects cotreatment, increases expression	2
Progesterone	affects cotreatment, decreases expression, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Asian ginseng	decreases expression, decreases reaction	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
cobaltous chloride	decreases secretion	1
triadimefon	increases expression	1
pentanal	increases expression	1
nefazodone	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5531564	Binding	Displacement of biotinylated ((2R,5S)-5-(4-chlorobenzyl)-4-(1-(pyridin-2-yl)piperidin-4-yl)morpholin-2-yl)methyl 41-oxo-45-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol4-yl)-4,7,10,13,16,19,22,25,28,31,34,37-dodecaoxa-40-azapentatet	Structure-Based Discovery of High-Affinity Small Molecule Ligands and Development of Tool Probes to Study the Role of Chitinase-3-Like Protein 1. — J Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1AB	Abcam THP-1 CHI3L1 KO	Cancer cell line	Male
CVCL_B6SF	HEK293 CHI3L1	Transformed cell line	Female
CVCL_D1RW	Abcam U-87MG CHI3L1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety