WNT1

Summary

WNT1 (Wnt family member 1, HGNC:12774) is a protein-coding gene on chromosome 12q13.12, encoding Proto-oncogene Wnt-1 (P04628). Ligand for members of the frizzled family of seven transmembrane receptors.

The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It is very conserved in evolution, and the protein encoded by this gene is known to be 98% identical to the mouse Wnt1 protein at the amino acid level. The studies in mouse indicate that the Wnt1 protein functions in the induction of the mesencephalon and cerebellum. This gene was originally considered as a candidate gene for Joubert syndrome, an autosomal recessive disorder with cerebellar hypoplasia as a leading feature. However, further studies suggested that the gene mutations might not have a significant role in Joubert syndrome. This gene is clustered with another family member, WNT10B, in the chromosome 12q13 region.

Source: NCBI Gene 7471 — RefSeq curated summary.

At a glance

• Gene–disease (curated): osteogenesis imperfecta type 15 (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 296 total — 22 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 18
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_005430

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12774
Approved symbol	WNT1
Name	Wnt family member 1
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000125084
Ensembl biotype	protein_coding
OMIM	164820
Entrez	7471

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000293549

RefSeq mRNA: 1 — MANE Select: NM_005430 NM_005430

CCDS: CCDS8776

Canonical transcript exons

ENST00000293549 — 4 exons

Exon	Start	End
ENSE00001114101	48981152	48982620
ENSE00001163542	48979468	48979721
ENSE00001187250	48980424	48980689
ENSE00001187256	48978322	48978754

Expression profiles

Bgee: expression breadth broad, 73 present calls, max score 73.15.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9966 / max 76.7488, expressed in 178 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125287	0.5335	132
125285	0.4079	118
125286	0.0552	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	73.15	gold quality
nucleus accumbens	UBERON:0001882	69.20	gold quality
superior frontal gyrus	UBERON:0002661	64.77	gold quality
frontal cortex	UBERON:0001870	62.33	gold quality
right frontal lobe	UBERON:0002810	61.67	gold quality
bone marrow cell	CL:0002092	60.98	gold quality
prefrontal cortex	UBERON:0000451	60.66	gold quality
putamen	UBERON:0001874	60.26	gold quality
vastus lateralis	UBERON:0001379	59.82	gold quality
quadriceps femoris	UBERON:0001377	59.78	gold quality
blood	UBERON:0000178	59.36	gold quality
caudate nucleus	UBERON:0001873	59.35	gold quality
bone marrow	UBERON:0002371	59.08	gold quality
Brodmann (1909) area 9	UBERON:0013540	58.94	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	58.59	gold quality
epithelium of bronchus	UBERON:0002031	58.19	gold quality
cerebral cortex	UBERON:0000956	57.86	gold quality
cerebellar vermis	UBERON:0004720	57.59	gold quality
lymph node	UBERON:0000029	55.98	gold quality
metanephric glomerulus	UBERON:0004736	55.97	gold quality
spleen	UBERON:0002106	54.24	gold quality
primary visual cortex	UBERON:0002436	54.19	gold quality
anterior cingulate cortex	UBERON:0009835	53.88	gold quality
duodenum	UBERON:0002114	52.92	gold quality
thymus	UBERON:0002370	52.59	silver quality
vermiform appendix	UBERON:0001154	52.25	gold quality
brain	UBERON:0000955	51.58	gold quality
central nervous system	UBERON:0001017	51.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	50.80	gold quality
small intestine	UBERON:0002108	50.65	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.76

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
EN1	Activation
FGF20	Unknown
LEF1	Unknown
LMX1A	Unknown
PITX3	Activation

Upstream regulators (CollecTRI, top): AR, ASCL1, DLX1, DLX2, DLX4, EMX2, EN1, ERG, FGF8, GBX2, HNF4A, HOXD3, LMX1A, LMX1B, MSX1, MTA1, NEUROD1, NFKB1, NFKBIA, NKX6-1, NKX6-2, OTX2, PAX2, PAX3, PAX5, PGR, POU3F1, POU3F3, POU4F1, RARA, SIX3, SUZ12, YY1, ZIC1

miRNA regulators (miRDB)

108 targeting WNT1, 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-4533	100.00	69.48	2758
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-6785-5P	99.82	68.68	4428

Literature-anchored findings (GeneRIF, showing 40)

• Wnt-1 but not epidermal growth factor induces beta-catenin/T-cell factor-dependent transcription in esophageal cancer cells. (PMID:11782388)
• Synergistic induction of tumor antigens by Wnt-1 signaling and retinoic acid revealed by gene expression profiling (PMID:11832495)
• The potential role of the WNT-1 gene in basal cell carcinoma seems to correlate with its ability to induce elevated cytoplasmic beta-catenin levels. (PMID:12014624)
• Data show that Wnt-1 induces expression of antiapoptotic genes in 3T3-L1 preadipocytes such as IGF-I and IGF-II, which allows these cells to resist apoptosis in response to serum deprivation. (PMID:12154096)
• Role of Wnt pathway in medulloblastoma oncogenesis: accumulation of beta-catenin in tumor cells was immunohistochemically proven in 5 cases; 2 cases showed positive immunoreactivity for Wnt-1 and another 2 showed mutation of either CTNNB1 or AXIN1 (PMID:12209999)
• Wnt signaling has a role in endothelial cell growth control and this is mediated through cell-cell contact (PMID:14644163)
• Wnt signal transduction through the Tak1 pathway phosphorylates and inhibits TCF, which might function as a feedback mechanism (PMID:14960582)
• CTNNB strongly increased activity of the eN/Nt5 promoter and this increase depended on the presence of TCF-1; demonstrated a link between Wnt signaling and the regulation of eN and ADA, which control the metabolism of adenosine (PMID:15149841)
• Wnt regulation of the Lef-1 promoter at the WRE may play an important role during airway submucosal glandular bud formation. (PMID:15194563)
• Oncogenic activation of the WNT/beta-catenin signaling pathway is common in hepatocellular carcinoma. (PMID:15580286)
• Causal relationship exists between aberrant Wnt-1 signaling and estrogen receptor+ mammary tumors (PMID:15824740)
• HCV core protein induces Huh-7 cell proliferation whether alone or in the context of HCV replication, which is at least partly mediated by transcriptional upregulation of growth-related genes, in particular wnt-1 (PMID:15841445)
• Wnt-1 blockade by either monoclonal antibody or siRNA induces cell death in sarcoma cells (PMID:15913453)
• Wnt-1, beta-catenin and APC expressions were related to the differentiation of oral squamous cell carcinoma. (PMID:16329837)
• aberrant Wnt signaling is a common event in NPC carcinogenesis linked with WIF-1 silencing (PMID:16427602)
• hAR is a direct target of LEF-1/TCF transcriptional regulation in PCa cells; expression of the hAR protein is suppressed by a degradation pathway regulated by cross-talk of Wnt, Akt, and PP2A (PMID:16474850)
• EGCG blocks Wnt signaling by inducing the HBP1 transcriptional repressor and inhibits aspects of invasive breast cancer (PMID:16495219)
• increased Wnt signaling, as achieved by ectopic expression of Wnt-1, triggers the DNA damage response and an ensuing cascade of events resulting in tumorigenic conversion of primary breast epithelial cells (PMID:16501043)
• the MED12 interface within Mediator is a new component in the Wnt/beta-catenin pathway (PMID:16565090)
• Wnt/beta-catenin activation was observed in 65% of pancreatic adenocarcinomas, independently of beta-catenin gene mutations in most tumors (PMID:16756720)
• beta-catenin level depends on the way and level of Wnt pathway activation (PMID:16760136)
• Wnt signaling activation significantly decreases the viability of retinoblastoma cell lines by inducing cell cycle arrest, which was associated with upregulated p53 (PMID:16930536)
• sFRP-1, a target gene of the hedgehog pathway, is involved in cross-talk between the hedgehog pathway and the Wnt pathway (PMID:17035233)
• The identification of a beta-catenin-T-cell factor-regulated Axin2-GSK3beta-Snail1 axis provides new mechanistic insights into cancer-associated epithelial-mesenchymal transition programmes. (PMID:17072303)
• Wnt/beta-catenin signaling has a role in neurodevelopment as well as in neurodegenerative diseases [review] (PMID:17143299)
• Wnt1 is critical for protection in the SH-SY5Y neuronal cell line against genomic DNA degradation, membrane phosphatidylserine (PS) exposure, and microglial activation. (PMID:17289346)
• Wnt1 signaling inhibits interfollicular progenitor cell growth and promotes terminal differentiation of keratinocytes. (PMID:17306035)
• importance of canonical Wnt signaling to mediate development of early hematoendothelial progenitors during human development (PMID:17875805)
• Wnt and epidermal growth factor receptor signaling pathways are altered through aberrant methylation and mutation in non small cell lung cancer (PMID:17947472)
• vascular Bmp Msx2 Wnt signaling and oxidative stress have roles in arterial calcification [review] (PMID:18056036)
• Silencing of WNT1 by siRNA induces apoptosis of MCF-7 human breast cancer cells. (PMID:18059186)
• Wnt1 overexpression affects the tumor proliferation in NSCLCs, partly via the upregulation of c-Myc (PMID:18097596)
• Wnt-1 strongly induced the expression of matricellular protein osteopontin, and modestly enhanced the expression of type I collagen in DPSCs. Unexpectedly, Wnt-1 inhibited alkaline phosphatase activity and the formation of mineralized nodules in DPSCs. (PMID:18218837)
• MesP1 drives vertebrate cardiovascular differentiation through Dkk-1-mediated blockade of Wnt-signalling (PMID:18297060)
• direct binding of NF-kappaB-p50 to the Wnt-1 promoter (PMID:18461473)
• A positive feedback stimulation of the Wnt pathway by activation of snail. (PMID:18469861)
• HIF-1alpha was found to inactivate the Wnt signaling by binding to hARD1 or beta-catenin, which may contribute to the hypoxia-induced growth arrest of tumor cells. (PMID:18593917)
• the Wnt/beta-catenin pathway contributes to carcinogenesis and cancer cell survival by driving expression of OPG (PMID:18676739)
• In the gastric cancerous tissues, the expression percentage of Wnt-1, beta-catenin and E-cadherin is 54.4%, 45.6%, 47.2%, respectively, which is significantly higher than the percentage expression of these genes in normal tissues (p<0.01). (PMID:18705344)
• RCK/ p54 might be a determinant of colorectal cancer proliferation by activating the canonical Wnt pathway (PMID:18769115)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	wnt1	ENSDARG00000055554
mus_musculus	Wnt1	ENSMUSG00000022997
rattus_norvegicus	Wnt1	ENSRNOG00000061818
drosophila_melanogaster	wg	FBGN0284084
caenorhabditis_elegans		WBGENE00000857

Paralogs (18): WNT16 (ENSG00000002745), WNT8A (ENSG00000061492), WNT8B (ENSG00000075290), WNT11 (ENSG00000085741), WNT2 (ENSG00000105989), WNT3 (ENSG00000108379), WNT5B (ENSG00000111186), WNT5A (ENSG00000114251), WNT6 (ENSG00000115596), WNT2B (ENSG00000134245), WNT10A (ENSG00000135925), WNT9A (ENSG00000143816), WNT3A (ENSG00000154342), WNT7A (ENSG00000154764), WNT9B (ENSG00000158955), WNT4 (ENSG00000162552), WNT10B (ENSG00000169884), WNT7B (ENSG00000188064)

Protein

Protein identifiers

Proto-oncogene Wnt-1 — P04628 (reviewed: P04628)

Alternative names: Proto-oncogene Int-1 homolog

All UniProt accessions (1): P04628

UniProt curated annotations — full annotation on UniProt →

Function. Ligand for members of the frizzled family of seven transmembrane receptors. Acts in the canonical Wnt signaling pathway by promoting beta-catenin-dependent transcriptional activation. In some developmental processes, is also a ligand for the coreceptor RYK, thus triggering Wnt signaling. Plays an essential role in the development of the embryonic brain and central nervous system (CNS). Has a role in osteoblast function, bone development and bone homeostasis.

Subunit / interactions. Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity. The complex with AFM may represent the physiological form in body fluids. Interacts with PORCN. Interacts with RSPO1, RSPO2 and RSPO3. Interacts with WLS.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Post-translational modifications. Palmitoleoylation is required for efficient binding to frizzled receptors. Palmitoleoylation is necessary for proper trafficking to cell surface. Depalmitoleoylated by NOTUM, leading to inhibit Wnt signaling pathway.

Disease relevance. Osteoporosis (OSTEOP) [MIM:166710] A systemic skeletal disorder characterized by decreased bone mass and deterioration of bone microarchitecture without alteration in the composition of bone. The result is fragile bones and an increased risk of fractures, even after minimal trauma. Osteoporosis is a chronic condition of multifactorial etiology and is usually clinically silent until a fracture occurs. Disease susceptibility is associated with variants affecting the gene represented in this entry. Osteogenesis imperfecta 15 (OI15) [MIM:615220] An autosomal recessive form of osteogenesis imperfecta, a disorder of bone formation characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI15 is characterized by early-onset recurrent fractures, bone deformity, significant reduction of bone density, short stature, and, in some patients, blue sclerae. Tooth development and hearing are normal. Learning and developmental delays and brain anomalies have been observed in some patients. The disease is caused by variants affecting the gene represented in this entry.

Polymorphism. Genetic variations in WNT1 define the bone mineral density quantitative trait locus 16 (BMND16) [MIM:615221]. Variance in bone mineral density influences bone mass, contributes to size determination in the general population, and is a susceptibility factor for osteoporotic fractures.

Similarity. Belongs to the Wnt family.

RefSeq proteins (1): NP_005421* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005817	Wnt	Family
IPR009139	Wnt1	Family
IPR018161	Wnt_CS	Conserved_site
IPR043158	Wnt_C	Homologous_superfamily

Pfam: PF00110

UniProt features (26 total): disulfide bond 11, sequence variant 8, glycosylation site 4, signal peptide 1, chain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04628-F1	86.53	0.73

Functional residue map

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

Post-translational modifications (1): 224

Disulfide bonds (11): 218–232, 220–227, 299–330, 315–325, 329–369, 345–360, 347–357, 352–353, 93–104, 143–151, 153–170

Glycosylation sites (4): 29, 316, 346, 359

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-201681	TCF dependent signaling in response to WNT
R-HSA-3238698	WNT ligand biogenesis and trafficking
R-HSA-373080	Class B/2 (Secretin family receptors)
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-4086400	PCP/CE pathway
R-HSA-4641262	Disassembly of the destruction complex and recruitment of AXIN to the membrane

MSigDB gene sets: 448 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_SPINAL_CORD_DEVELOPMENT, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_METENCEPHALON_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3

GO Biological Process (59): embryonic axis specification (GO:0000578), branching involved in ureteric bud morphogenesis (GO:0001658), cell-cell signaling (GO:0007267), myoblast fusion (GO:0007520), positive regulation of cell population proliferation (GO:0008284), response to wounding (GO:0009611), positive regulation of lamellipodium assembly (GO:0010592), negative regulation of cell-substrate adhesion (GO:0010812), Wnt signaling pathway (GO:0016055), spinal cord association neuron differentiation (GO:0021527), diencephalon development (GO:0021536), central nervous system morphogenesis (GO:0021551), cerebellum formation (GO:0021588), forebrain anterior/posterior pattern specification (GO:0021797), midbrain-hindbrain boundary maturation during brain development (GO:0022004), negative regulation of cell-cell adhesion (GO:0022408), neuron differentiation (GO:0030182), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), negative regulation of BMP signaling pathway (GO:0030514), midbrain development (GO:0030901), animal organ regeneration (GO:0031100), T cell differentiation in thymus (GO:0033077), cell proliferation in midbrain (GO:0033278), astrocyte-dopaminergic neuron signaling (GO:0036520), inner ear morphogenesis (GO:0042472), signal transduction in response to DNA damage (GO:0042770), negative regulation of apoptotic process (GO:0043066), positive regulation of insulin-like growth factor receptor signaling pathway (GO:0043568), cell fate commitment (GO:0045165), fat cell differentiation (GO:0045444), negative regulation of fat cell differentiation (GO:0045599), positive regulation of Notch signaling pathway (GO:0045747), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of fibroblast proliferation (GO:0048146), neuron fate determination (GO:0048664), Spemann organizer formation (GO:0060061), canonical Wnt signaling pathway (GO:0060070), bone development (GO:0060348), positive regulation of dermatome development (GO:0061184)

GO Molecular Function (6): frizzled binding (GO:0005109), cytokine activity (GO:0005125), morphogen activity (GO:0016015), protein domain specific binding (GO:0019904), receptor ligand activity (GO:0048018), signaling receptor binding (GO:0005102)

GO Cellular Component (9): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), endoplasmic reticulum lumen (GO:0005788), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), cell surface (GO:0009986), endocytic vesicle membrane (GO:0030666), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by WNT	2
GPCR ligand binding	1
Adipogenesis	1
Beta-catenin independent WNT signaling	1
TCF dependent signaling in response to WNT	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
negative regulation of cell adhesion	2
anatomical structure development	2
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	2
receptor ligand activity	2
protein binding	2
intracellular organelle lumen	2
axis specification	1
embryonic pattern specification	1
branching morphogenesis of an epithelial tube	1
ureteric bud morphogenesis	1
cell communication	1
signaling	1
syncytium formation by cell-cell fusion	1
myotube differentiation	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
response to stress	1
regulation of lamellipodium assembly	1
lamellipodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
positive regulation of lamellipodium organization	1
regulation of cell-substrate adhesion	1
cell-substrate adhesion	1
cell surface receptor signaling pathway	1
cell differentiation in spinal cord	1
dorsal spinal cord development	1
central nervous system neuron differentiation	1
forebrain development	1
central nervous system development	1
anatomical structure morphogenesis	1
hindbrain formation	1
cerebellum morphogenesis	1
anatomical structure formation involved in morphogenesis	1
anterior/posterior pattern specification	1
forebrain regionalization	1
midbrain-hindbrain boundary maturation	1
multicellular organismal process	1
regulation of cell-cell adhesion	1

Protein interactions and networks

STRING

2490 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WNT1	LRP6	O75581	998
WNT1	LRP5	O75197	997
WNT1	FZD1	Q9UP38	971
WNT1	CTNNB1	P35222	944
WNT1	FZD8	Q9H461	923
WNT1	SFRP1	Q8N474	915
WNT1	DKK1	O94907	900
WNT1	DVL1	O14640	893
WNT1	GBX2	P52951	881
WNT1	PORCN	Q9H237	849
WNT1	FZD7	O75084	841
WNT1	FZD10	Q9ULW2	835
WNT1	AXIN1	O15169	831
WNT1	HNF4A	P41235	827
WNT1	RYK	P34925	824

IntAct

5 interactions, top by confidence:

A	B	Type	Score
WNT1	UBR3	psi-mi:“MI:0915”(physical association)	0.400
WNT1	AFM	psi-mi:“MI:0915”(physical association)	0.400
WNT1	WLS	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (11): UBR3 (Affinity Capture-MS), SFRP1 (Affinity Capture-Western), UBR3 (Affinity Capture-MS), WNT1 (Affinity Capture-RNA), WNT1 (Affinity Capture-RNA), WNT1 (Affinity Capture-MS), WNT1 (Affinity Capture-Western), WNT1 (Affinity Capture-Western), WNT1 (Affinity Capture-MS), WNT1 (Reconstituted Complex), FZD8 (Reconstituted Complex)

ESM2 similar proteins: B2GUT4, O00744, O13267, O42237, O73864, O96014, P04426, P04628, P09615, P10108, P10600, P17125, P21551, P22724, P22725, P22726, P24257, P31286, P33945, P41221, P43446, P47793, P48614, P48615, P49337, P49338, P49339, P49340, P49893, P51891, P56705, P70275, P87387, Q06442, Q06443, Q07258, Q27Q52, Q28J82, Q4VC17, Q5NVK2

Diamond homologs: A0M8S1, A0M8T2, A1X153, A4D7S0, B2GUT4, O00755, O13267, O15978, O42122, O70283, P04426, P04628, P09544, P09615, P10108, P17553, P21551, P21552, P22724, P22725, P22726, P22727, P24257, P24383, P27467, P28047, P28465, P31285, P31286, P33945, P34888, P34889, P41221, P43446, P47793, P49337, P49338, P49339, P49340, P49893

SIGNOR signaling

26 interactions.

A	Effect	B	Mechanism
WNT1	up-regulates	FZD8	binding
WNT1	up-regulates	RYK	binding
WNT1	“up-regulates activity”	FZD1	binding
WNT1	“up-regulates activity”	FZD3	binding
WNT1	“up-regulates activity”	LRP5	binding
WNT1	“up-regulates activity”	LRP6	binding
WNT1	“up-regulates activity”	PRKACA
WNT1	“up-regulates activity”	FZD6	binding
FASN	“up-regulates activity”	WNT1
hsa-miR-22-5p	“down-regulates quantity by repression”	WNT1	“post transcriptional regulation”
hsa-miR-200b-5p	“down-regulates quantity by repression”	WNT1	“post transcriptional regulation”
hsa-miR-148a-5p	“down-regulates quantity by repression”	WNT1	“post transcriptional regulation”
hsa-miR-148a-3p	“down-regulates quantity by repression”	WNT1	“post transcriptional regulation”
FRZB	down-regulates	WNT1	binding
SFRP1	down-regulates	WNT1	binding
WNT1	“up-regulates activity”	MYF5
SOSTDC1	“down-regulates activity”	WNT1
WNT1	“up-regulates activity”	Frizzled	binding
ERG	“up-regulates quantity by expression”	WNT1	“transcriptional regulation”
WNT1	up-regulates	CTNNB1

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — UCS.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	22
Likely pathogenic	19
Uncertain significance	168
Likely benign	68
Benign	1

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1332774	NM_005430.4(WNT1):c.506dup (p.Cys170fs)	Pathogenic
1371714	NM_005430.4(WNT1):c.499dup (p.Trp167fs)	Pathogenic
1388996	NM_005430.4(WNT1):c.479_480del (p.Pro160fs)	Pathogenic
1424085	NM_005430.4(WNT1):c.1005_1027del (p.Thr336fs)	Pathogenic
1427519	NM_005430.4(WNT1):c.907G>T (p.Gly303Ter)	Pathogenic
1459965	NM_005430.4(WNT1):c.287_300del (p.Gln96fs)	Pathogenic
1708283	NM_005430.4(WNT1):c.465C>A (p.Tyr155Ter)	Pathogenic
180210	NM_005430.4(WNT1):c.1026del (p.Glu343fs)	Pathogenic
2117080	NM_005430.4(WNT1):c.3G>A (p.Met1Ile)	Pathogenic
2169566	NM_005430.4(WNT1):c.104+1G>A	Pathogenic
2438690	NM_005430.4(WNT1):c.255del (p.Leu86fs)	Pathogenic
2706200	NM_005430.4(WNT1):c.707del (p.Leu236fs)	Pathogenic
2708745	NM_005430.4(WNT1):c.578del (p.Asp193fs)	Pathogenic
2746657	NM_005430.4(WNT1):c.102G>A (p.Trp34Ter)	Pathogenic
2766525	NM_005430.4(WNT1):c.547del (p.Glu183fs)	Pathogenic
2853704	NM_005430.4(WNT1):c.953C>A (p.Ser318Ter)	Pathogenic
3693886	NM_005430.4(WNT1):c.1035C>A (p.Cys345Ter)	Pathogenic
3721134	NM_005430.4(WNT1):c.990C>A (p.Cys330Ter)	Pathogenic
489252	NM_005430.4(WNT1):c.364C>T (p.Arg122Ter)	Pathogenic
50258	NM_005430.4(WNT1):c.624+4A>G	Pathogenic
50259	NM_005430.4(WNT1):c.565G>T (p.Glu189Ter)	Pathogenic
50261	NM_005430.4(WNT1):c.946_949dup (p.Ser317fs)	Pathogenic
1224436	NM_005430.4(WNT1):c.480del (p.Gly162fs)	Likely pathogenic
1299523	NM_005430.4(WNT1):c.617G>A (p.Gly206Asp)	Likely pathogenic
1683629	NM_005430.4(WNT1):c.860dup (p.His287fs)	Likely pathogenic
1687618	NM_005430.4(WNT1):c.893T>G (p.Phe298Cys)	Likely pathogenic
2434662	NM_005430.4(WNT1):c.331dup (p.His111fs)	Likely pathogenic
2636643	NM_005430.4(WNT1):c.6del (p.Leu3fs)	Likely pathogenic
2735849	NM_005430.4(WNT1):c.529G>T (p.Gly177Cys)	Likely pathogenic
3336151	NM_005430.4(WNT1):c.397G>A (p.Ala133Thr)	Likely pathogenic

SpliceAI

589 predictions. Top by Δscore:

Variant	Effect	Δscore
12:48980418:CCACA:C	acceptor_loss	1.0000
12:48980421:CAGGC:C	acceptor_loss	1.0000
12:48980422:A:AG	acceptor_gain	1.0000
12:48980423:G:GA	acceptor_gain	1.0000
12:48980423:G:GT	acceptor_loss	1.0000
12:48980423:GGCT:G	acceptor_gain	1.0000
12:48980681:GGCC:G	donor_gain	1.0000
12:48980682:GCCG:G	donor_gain	1.0000
12:48981148:GCA:G	acceptor_loss	1.0000
12:48981150:A:AC	acceptor_loss	1.0000
12:48981151:G:A	acceptor_loss	1.0000
12:48981151:GACC:G	acceptor_gain	1.0000
12:48978752:GTG:G	donor_gain	0.9900
12:48978755:GTA:G	donor_loss	0.9900
12:48978756:T:A	donor_loss	0.9900
12:48979721:GGTG:G	donor_loss	0.9900
12:48979722:G:C	donor_loss	0.9900
12:48979723:T:G	donor_loss	0.9900
12:48980422:AG:A	acceptor_gain	0.9900
12:48980422:AGGCT:A	acceptor_gain	0.9900
12:48980423:GG:G	acceptor_gain	0.9900
12:48980423:GGC:G	acceptor_gain	0.9900
12:48980423:GGCTG:G	acceptor_gain	0.9900
12:48980679:C:T	donor_gain	0.9900
12:48981150:A:AG	acceptor_gain	0.9900
12:48981150:AGACC:A	acceptor_gain	0.9900
12:48981151:G:GT	acceptor_gain	0.9900
12:48981151:GA:G	acceptor_gain	0.9900
12:48981151:GACCG:G	acceptor_gain	0.9900
12:48978755:G:GG	donor_gain	0.9800

AlphaMissense

2386 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:48979667:T:A	W102R	1.000
12:48979667:T:C	W102R	1.000
12:48979669:G:C	W102C	1.000
12:48979669:G:T	W102C	1.000
12:48980451:C:A	A129D	1.000
12:48980492:T:A	C143S	1.000
12:48980493:G:A	C143Y	1.000
12:48980493:G:C	C143S	1.000
12:48980494:C:G	C143W	1.000
12:48980517:G:A	C151Y	1.000
12:48980560:G:C	W165C	1.000
12:48980560:G:T	W165C	1.000
12:48980566:G:C	W167C	1.000
12:48980566:G:T	W167C	1.000
12:48980573:T:A	C170S	1.000
12:48980574:G:C	C170S	1.000
12:48980616:T:G	F184C	1.000
12:48980671:C:A	N202K	1.000
12:48980671:C:G	N202K	1.000
12:48981184:G:C	K219N	1.000
12:48981184:G:T	K219N	1.000
12:48981185:T:A	C220S	1.000
12:48981186:G:C	C220S	1.000
12:48981226:G:C	W233C	1.000
12:48981226:G:T	W233C	1.000
12:48981572:T:C	F349L	1.000
12:48981573:T:G	F349C	1.000
12:48981574:C:A	F349L	1.000
12:48981574:C:G	F349L	1.000
12:48981580:G:C	W351C	1.000

dbSNP variants (sampled 300 via entrez): RS1000085196 (12:48979171 T>A), RS1000192480 (12:48977424 C>T), RS1000878726 (12:48977039 G>A), RS1001037839 (12:48980280 G>A), RS1001244752 (12:48978357 T>C,G), RS1001359373 (12:48978161 C>A,G,T), RS1001483697 (12:48978380 G>A,T), RS1003032872 (12:48976383 C>T), RS1004271600 (12:48982959 T>G), RS1004659235 (12:48978287 T>G), RS1005097238 (12:48978117 G>A), RS1005419344 (12:48981241 G>A,C), RS1005471724 (12:48980919 T>C), RS1006002835 (12:48976414 A>T), RS1006469835 (12:48982563 C>G,T)

Disease associations

OMIM: gene MIM:164820 | disease phenotypes: MIM:166200, MIM:615220, MIM:148300, MIM:259420

GenCC curated gene-disease

Disease	Classification	Inheritance
osteogenesis imperfecta type 15	Definitive	Autosomal recessive
idiopathic juvenile osteoporosis	Strong	Autosomal dominant
osteogenesis imperfecta type 3	Supportive	Autosomal dominant
osteogenesis imperfecta type 4	Supportive	Autosomal dominant

Mondo (7): osteogenesis imperfecta (MONDO:0019019), osteogenesis imperfecta type 15 (MONDO:0014086), connective tissue disorder (MONDO:0003900), keratoconus (MONDO:0015486), osteogenesis imperfecta type 3 (MONDO:0009804), idiopathic juvenile osteoporosis (MONDO:0019409), osteogenesis imperfecta type 4 (MONDO:0008148)

Orphanet (5): Osteogenesis imperfecta (Orphanet:666), Idiopathic juvenile osteoporosis (Orphanet:85193), Osteogenesis imperfecta type 3 (Orphanet:216812), OBSOLETE: Keratoconus (Orphanet:156071), NON RARE IN EUROPE: Isolated keratoconus (Orphanet:2335)

HPO phenotypes

18 total (19 of 18 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000592	Blue sclerae
HP:0000883	Thin ribs
HP:0000926	Platyspondyly
HP:0000939	Osteoporosis
HP:0001263	Global developmental delay
HP:0001288	Gait disturbance
HP:0001321	Cerebellar hypoplasia
HP:0001382	Joint hypermobility
HP:0002650	Scoliosis
HP:0002653	Bone pain
HP:0002757	Recurrent fractures
HP:0002808	Kyphosis
HP:0002953	Vertebral compression fracture
HP:0003023	Bowing of limbs due to multiple fractures
HP:0004322	Short stature
HP:0010636	Schizencephaly
HP:0012110	Hypoplasia of the pons
HP:0000563	Keratoconus

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST006288_12	Heel bone mineral density	3.000000e-36
GCST006288_197	Heel bone mineral density	3.000000e-18
GCST006288_388	Heel bone mineral density	2.000000e-18
GCST006979_898	Heel bone mineral density	1.000000e-19
GCST006979_899	Heel bone mineral density	7.000000e-17
GCST006979_900	Heel bone mineral density	8.000000e-144
GCST008103_109	Bipolar disorder	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D003240	Connective Tissue Diseases	C17.300
D007640	Keratoconus	C11.204.627
D010013	Osteogenesis Imperfecta	C05.116.099.708.685; C16.320.737; C17.300.200.540
C537700	Juvenile osteoporosis (supp.)
C536044	Osteogenesis imperfecta, type 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1255129 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 34 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL4784318	CIRTUVIVINT	1	34

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

Binding affinities (BindingDB)

566 measured of 691 human assays (691 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[5-[3-[7-(5-fluorothiophen-2-yl)-1H-imidazo[4,5-b]pyridin-2-yl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-5-yl]-3-pyridinyl]-2,2-dimethylpropanamide	IC50	0.4 nM	US-10280166: 2-(1H-indazol-3-yl)-3H-imidazo[4,5-B]pyridine and therapeutic uses thereof
N-[6-(1-methyltriazol-4-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	0.4 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
2,2-dimethyl-N-[5-[3-[7-(5-methylthiophen-2-yl)-1H-imidazo[4,5-b]pyridin-2-yl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-5-yl]-3-pyridinyl]propanamide	IC50	0.6 nM	US-10280166: 2-(1H-indazol-3-yl)-3H-imidazo[4,5-B]pyridine and therapeutic uses thereof
1-(2-hydroxyethyl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	0.6 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-methoxy-N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	0.8 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]-1-(3,3,3-trifluoropropyl)piperidine-4-carboxamide	EC50	0.9 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-(hydroxymethyl)-N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	0.9 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-(dimethylamino)-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	0.9 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-(2-pyrrolidin-1-ylacetyl)-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	0.9 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[5-[3-[7-(3-fluorophenyl)-1H-imidazo[4,5-b]pyridin-2-yl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-5-yl]-3-pyridinyl]cyclopropanecarboxamide	IC50	1 nM	US-10280166: 2-(1H-indazol-3-yl)-3H-imidazo[4,5-B]pyridine and therapeutic uses thereof
N-[5-[3-(7-thiophen-3-yl-1H-imidazo[4,5-b]pyridin-2-yl)-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-5-yl]-3-pyridinyl]butanamide	IC50	1 nM	US-10280166: 2-(1H-indazol-3-yl)-3H-imidazo[4,5-B]pyridine and therapeutic uses thereof
4-[(3-fluoroazetidin-1-yl)methyl]-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	1 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-(oxetan-3-yl)-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	1 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-(1-methylpiperidin-4-yl)-N-[6-(1-methyltriazol-4-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	1.1 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-(2,2-difluoropropyl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	1.2 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-(hydroxymethyl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	1.2 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-[(4-methylpiperazin-1-yl)methyl]-N-[6-(1-methyltriazol-4-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	1.2 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-[[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]carbamoyl]cyclohexane-1-carboxylic acid	EC50	1.2 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]-4-morpholin-4-ylcyclohexane-1-carboxamide	EC50	1.3 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-[(3-fluoroazetidin-1-yl)methyl]-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	1.3 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-(2,2-difluoroethyl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	1.3 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4,4-difluoro-N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	1.3 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-methyl-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	1.3 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-(1-methylpiperidin-4-yl)-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	1.3 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-(2-fluoro-2-methylpropyl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	1.4 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]-1-(2-methylpropyl)piperidine-4-carboxamide	EC50	1.4 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-(2,2-difluoropropyl)-N-[6-(1,3-thiazol-5-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	1.4 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-(hydroxymethyl)-N-[6-(5-methyl-1,3,4-thiadiazol-2-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	1.4 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-(4-methylpiperazine-1-carbonyl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	1.4 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-[(4-methylpiperazin-1-yl)methyl]-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	1.5 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-(2-fluoroethyl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	1.5 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]-1-(3,3,3-trifluoropropyl)piperidine-4-carboxamide	EC50	1.5 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]-1-methylsulfonylpiperidine-4-carboxamide	EC50	1.5 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	1.5 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-(2-methylpropyl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	1.6 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]-1-methylsulfonylpiperidine-4-carboxamide	EC50	1.6 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
methyl 2-[4-[[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]carbamoyl]piperidin-1-yl]acetate	EC50	1.6 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-fluoro-N-[6-(3-methylimidazol-4-yl)isoquinolin-3-yl]cyclopropane-1-carboxamide	EC50	1.6 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-methyl-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	1.7 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
4-(dimethylamino)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	1.7 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
methyl 4-[[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]carbamoyl]cyclohexane-1-carboxylate	EC50	1.7 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
5-[3-[7-(2-fluorophenyl)-1H-imidazo[4,5-b]pyridin-2-yl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-5-yl]pyridin-3-amine	IC50	1.8 nM	US-10280166: 2-(1H-indazol-3-yl)-3H-imidazo[4,5-B]pyridine and therapeutic uses thereof
4-methoxy-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]cyclohexane-1-carboxamide	EC50	1.8 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-(1-methylpiperidin-4-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	1.8 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-(2-methylpropyl)-N-[6-(1H-pyrazol-4-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	1.8 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]oxane-4-carboxamide	EC50	1.9 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]-1-[(2S)-3,3,3-trifluoro-2-methylpropyl]piperidine-4-carboxamide	EC50	1.9 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
1-benzoyl-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]piperidine-4-carboxamide	EC50	1.9 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
(2S)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]piperidine-2-carboxamide	EC50	1.9 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof
N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]-1-(1,3-oxazol-2-ylmethyl)piperidine-4-carboxamide	EC50	1.9 nM	US-10287267: Isoquinolin-3-yl carboxamides and preparation and use thereof

ChEMBL bioactivities

1203 potent at pChembl≥5 of 1205 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.40	IC50	0.4	nM	CHEMBL4776636
9.22	IC50	0.6	nM	CHEMBL6017060
9.00	IC50	1	nM	CHEMBL5840522
9.00	IC50	1	nM	CHEMBL4784131
8.74	IC50	1.8	nM	CHEMBL4758175
8.70	IC50	2	nM	CHEMBL4788446
8.70	IC50	2	nM	CHEMBL6064555
8.70	IC50	2	nM	CHEMBL5899410
8.64	IC50	2.3	nM	CHEMBL5834735
8.52	IC50	3	nM	CHEMBL5834011
8.52	IC50	3	nM	CHEMBL6011267
8.52	IC50	3	nM	CHEMBL6021805
8.46	IC50	3.5	nM	CHEMBL5930385
8.46	IC50	3.5	nM	CHEMBL5745701
8.40	IC50	4	nM	CHEMBL5833441
8.40	IC50	4	nM	CHEMBL4761354
8.38	IC50	4.2	nM	CHEMBL5950995
8.37	IC50	4.3	nM	CHEMBL6035880
8.35	IC50	4.5	nM	CHEMBL4759401
8.33	IC50	4.7	nM	CHEMBL5981709
8.31	IC50	4.9	nM	CHEMBL5874270
8.30	IC50	5	nM	CHEMBL5989335
8.30	IC50	5	nM	CHEMBL5985222
8.30	IC50	5	nM	CHEMBL4779515
8.29	IC50	5.1	nM	CHEMBL5784209
8.29	IC50	5.1	nM	CHEMBL5840236
8.28	IC50	5.2	nM	CHEMBL6065936
8.24	IC50	5.8	nM	CHEMBL5978822
8.24	IC50	5.8	nM	CHEMBL5752117
8.22	IC50	6	nM	CHEMBL5825094
8.22	IC50	6	nM	CHEMBL5841397
8.21	IC50	6.2	nM	CHEMBL5913216
8.21	IC50	6.1	nM	CHEMBL5786507
8.20	IC50	6.3	nM	CHEMBL6016383
8.19	IC50	6.5	nM	CHEMBL5959925
8.19	IC50	6.4	nM	CHEMBL5932153
8.17	IC50	6.8	nM	CHEMBL4787474
8.17	IC50	6.8	nM	CHEMBL5799605
8.17	IC50	6.7	nM	CHEMBL6046971
8.16	IC50	6.9	nM	CHEMBL6056647
8.15	IC50	7	nM	CHEMBL4785547
8.13	IC50	7.4	nM	CHEMBL5812830
8.11	IC50	7.7	nM	CHEMBL4764391
8.09	IC50	8.1	nM	CHEMBL5964831
8.08	IC50	8.4	nM	CHEMBL6056854
8.06	IC50	8.8	nM	CHEMBL5758753
8.05	IC50	9	nM	CHEMBL5962798
8.04	IC50	9.1	nM	CHEMBL5894511
8.03	IC50	9.4	nM	CHEMBL5821642
8.01	IC50	9.8	nM	CHEMBL5860356

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, affects expression	2
Valproic Acid	affects cotreatment, increases expression, affects expression	2
ETC-159	decreases expression	1
lead acetate	affects cotreatment, decreases expression	1
ascorbate-2-phosphate	affects cotreatment, increases expression, decreases reaction	1
arsenite	increases methylation	1
chromous chloride	affects cotreatment, decreases expression	1
lead nitrate	affects cotreatment, decreases reaction, increases expression	1
linalool	increases expression	1
diethanolamine	increases expression	1
monomethylarsonic acid	affects cotreatment, affects expression	1
chromic oxide	affects cotreatment, decreases expression	1
ochratoxin A	increases expression	1
beta-glycerophosphoric acid	affects cotreatment, increases expression, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
tocotrienol, delta	decreases expression	1
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases reaction, increases expression	1
quinocetone	decreases expression, decreases reaction	1
LGK974	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	affects expression, affects reaction	1
Microplastics	decreases expression, increases abundance	1
Acetylcysteine	decreases expression, decreases reaction	1
Benzo(a)pyrene	affects methylation	1
Cacodylic Acid	affects cotreatment, affects expression	1
Cadmium	decreases expression	1
Dexamethasone	affects cotreatment, increases expression, decreases reaction	1
Diethylhexyl Phthalate	decreases expression	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650415	Binding	Inhibition of WNT1 (unknown origin) at 0.3 uM incubated for 6 hrs by ingenuity upstream regulator analysis	Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours. — Nature

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00131469	PHASE4	COMPLETED	Study of Teriparatide (FORTEO) to Treat Adults With Osteogenesis Imperfecta
NCT00159419	PHASE4	COMPLETED	Bisphosphonate Therapy for Osteogenesis Imperfecta
NCT01713231	PHASE4	COMPLETED	Effect of High-Dose Vitamin D on Bone Density in Osteogenesis Imperfecta
NCT02303873	PHASE4	COMPLETED	Efficacy and Safety of Alendronate in Chinese Children or Adolescents With Osteogenesis Imperfecta
NCT03735537	PHASE4	COMPLETED	Treatment of Osteogenesis Imperfecta With Parathyroid Hormone and Zoledronic Acid
NCT04152551	PHASE4	RECRUITING	Effects of Bisphosphonates on OI-Related Hearing Loss
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT01485211	PHASE4	COMPLETED	Corneal Thickness Changes During Corneal Collagen Cross-linking With Ultraviolet-A Irradiation and Riboflavin
NCT02119039	PHASE4	COMPLETED	Effect of CACICOL20 on Corneal Epithelial Healing After Cross-linking in Patients With Keratoconus
NCT03245853	PHASE4	COMPLETED	Epi-On Corneal Crosslinking for Keratoconus
NCT03429569	PHASE4	UNKNOWN	Cross-Linking ACcéléré Iontophorèse Confocal kératocONE
NCT04427956	PHASE4	COMPLETED	Corneal Crosslinking Treatment Study
NCT07474870	PHASE4	NOT_YET_RECRUITING	Outcomes of CTAK Surgery
NCT00001305	PHASE3	COMPLETED	Growth Hormone Therapy in Osteogenesis Imperfecta
NCT00005901	PHASE3	COMPLETED	Pamidronate to Treat Osteogenesis Imperfecta in Children
NCT00106028	PHASE3	COMPLETED	Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children
NCT00982124	PHASE3	COMPLETED	An Efficacy and Safety Trial of Intravenous Zoledronic Acid in Infants Less Than One Year of Age, With Severe Osteogenesis Imperfecta
NCT02352753	PHASE3	TERMINATED	Multicenter,Single-arm Study to Evaluate Efficacy, Safety, & Pharmacokinetics of Denosumab in Children w/ OI
NCT03638128	PHASE3	TERMINATED	Open-label Extension of Study 20130173 of Denosumab in Children and Young Adults With Osteogenesis Imperfecta
NCT05768854	PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta
NCT05972551	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate Efficacy and Safety of Romosozumab Compared With Bisphosphonates in Children and Adolescents With Osteogenesis Imperfecta
NCT06636071	PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab in Pediatric Japanese Subjects With Osteogenesis Imperfecta
NCT07366086	PHASE3	RECRUITING	Pediatric Safety Follow-up Study of Prior Treatment With Romosozumab for Osteogenesis Imperfecta
NCT00864201	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06716606	PHASE3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT00371202	PHASE3	UNKNOWN	Comparison of Penetrating Keratoplasty and Deep Lamellar Keratoplasty With the Big Bubble Technique for Keratoconus