SORT1

Summary

SORT1 (sortilin 1, HGNC:11186) is a protein-coding gene on chromosome 1p13.3, encoding Sortilin (Q99523). Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface.

This gene encodes a member of the VPS10-related sortilin family of proteins. The encoded preproprotein is proteolytically processed by furin to generate the mature receptor. This receptor plays a role in the trafficking of different proteins to either the cell surface, or subcellular compartments such as lysosomes and endosomes. Expression levels of this gene may influence the risk of myocardial infarction in human patients. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 6272 — RefSeq curated summary.

At a glance

• GWAS associations: 44
• Clinical variants (ClinVar): 99 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002959

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11186
Approved symbol	SORT1
Name	sortilin 1
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	Gp95, NT3
Ensembl gene	ENSG00000134243
Ensembl biotype	protein_coding
OMIM	602458
Entrez	6272

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 18 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000256637, ENST00000466471, ENST00000471996, ENST00000482236, ENST00000483508, ENST00000485149, ENST00000493736, ENST00000495777, ENST00000538502, ENST00000633956, ENST00000902724, ENST00000902725, ENST00000902726, ENST00000902727, ENST00000934841, ENST00000934842, ENST00000934843, ENST00000934844, ENST00000957898, ENST00000957899, ENST00000957900, ENST00000957901, ENST00000957902

RefSeq mRNA: 2 — MANE Select: NM_002959 NM_001205228, NM_002959

CCDS: CCDS55618, CCDS798

Canonical transcript exons

ENST00000256637 — 20 exons

Exon	Start	End
ENSE00000912895	109350929	109351002
ENSE00000912897	109347483	109347532
ENSE00000912899	109345751	109345881
ENSE00000912900	109342014	109342158
ENSE00000912902	109340724	109340879
ENSE00000912904	109336240	109336346
ENSE00000912908	109326992	109327160
ENSE00000912912	109322932	109323121
ENSE00000912914	109317853	109317969
ENSE00000958074	109397587	109397918
ENSE00001124417	109314261	109314384
ENSE00001152424	109316850	109316958
ENSE00001152449	109324899	109325089
ENSE00001348032	109309575	109314057
ENSE00003483084	109314672	109314778
ENSE00003483854	109367408	109367481
ENSE00003493181	109369530	109369589
ENSE00003496428	109355367	109355469
ENSE00003629480	109327499	109327601
ENSE00003682938	109354367	109354531

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.5644 / max 3421.2063, expressed in 1732 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13703	40.1193	1709
13704	2.6671	1186
13688	1.4330	660
13698	0.4474	188
13695	0.3556	90
13699	0.1878	100
13702	0.1872	80
13700	0.1020	38
13697	0.0649	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	99.32	gold quality
corpus epididymis	UBERON:0004359	99.08	gold quality
subthalamic nucleus	UBERON:0001906	99.06	gold quality
postcentral gyrus	UBERON:0002581	98.94	gold quality
parietal lobe	UBERON:0001872	98.83	gold quality
globus pallidus	UBERON:0001875	98.74	gold quality
lateral globus pallidus	UBERON:0002476	98.74	gold quality
medial globus pallidus	UBERON:0002477	98.68	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.61	gold quality
corpus callosum	UBERON:0002336	98.54	gold quality
superior vestibular nucleus	UBERON:0007227	98.37	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.35	gold quality
middle temporal gyrus	UBERON:0002771	98.34	gold quality
ventral tegmental area	UBERON:0002691	98.33	gold quality
substantia nigra pars compacta	UBERON:0001965	98.20	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.01	gold quality
entorhinal cortex	UBERON:0002728	97.98	gold quality
superior frontal gyrus	UBERON:0002661	97.85	gold quality
pons	UBERON:0000988	97.74	gold quality
spinal cord	UBERON:0002240	97.74	gold quality
right coronary artery	UBERON:0001625	97.65	gold quality
epididymis	UBERON:0001301	97.46	gold quality
popliteal artery	UBERON:0002250	97.32	gold quality
primary visual cortex	UBERON:0002436	97.32	gold quality
tibial artery	UBERON:0007610	97.32	gold quality
parotid gland	UBERON:0001831	97.30	gold quality
Ammon’s horn	UBERON:0001954	97.15	gold quality
coronary artery	UBERON:0001621	97.10	gold quality
aorta	UBERON:0000947	97.09	gold quality
left coronary artery	UBERON:0001626	97.04	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	10.90
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF3, ESR1

miRNA regulators (miRDB)

206 targeting SORT1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797

Literature-anchored findings (GeneRIF, showing 40)

• Neurotensin receptor-1 and -3 complex modulates the cellular signaling of neurotensin in the HT29 cell line. (PMID:12360476)
• The shedding of the membrane NTR3 leads to a soluble protein able to bind exogenous NT, suggesting a role of this process in the biological activity of the peptide. (PMID:12419319)
• The trafficking of SAPs is dependent on sortilin, demonstrating a novel lysosomal trafficking. (PMID:14657016)
• Neurotensin receptor-3 exists in two distinct forms in HT29 cells: a high molecular weight, membrane-associated form responsible for neurotensin endocytosis from the cell surface and a lower molecular weight, intracellular form. (PMID:15313463)
• the luminal Vps10p domain of sortilin plays the predominant role in targeting to insulin-responsive Glut4-containing vesicles (PMID:17220298)
• sortilin and mannose-6-phosphate receptors recycle to the TGN in SNX1-dependent carriers, which we named endosome-to-TGN transport carriers (PMID:18088323)
• the N-terminal Vps10p domain of sortilin, which is responsible for the interaction with the neurotrophins, adopts a beta-propeller fold, and that the N-terminal regions of sortilin, pro-NGF and pro-BDNF are mainly intrinsically disordered regions (PMID:18191449)
• apoA-V binds to receptors possessing LDL-A repeats and Vsp10p domains, including SorLA and Sortilin, and apoA-V is internalized into cells via these receptors (PMID:18603531)
• NT autocrine and/or paracrine stimulation mediated by NTR3 may be a mechanism associated with the tumourigenesis of functioning adenomas. (PMID:18624930)
• in mature B cell lines, an autocrine BDNF production is up-regulated by stress culture conditions and exerts a modulation of apoptosis through the sortilin pathway (PMID:18713973)
• Sortilin, an essential player in adipocyte and muscle glucose metabolism through the control of GLUT4 localisation, is downregulated in obesity and TNF-alpha is likely to be involved in this defect. (PMID:19219422)
• WNK4 promotes sodium chloride co-transporter targeting to the lysosome for degradation via a mechanism involving sortilin. (PMID:19875813)
• explored the binding characteristics of proNGF to sortilin using surface plasmon resonance and cell-based assays and determined that calcium ions promote the formation of a stable ternary complex of proNGF-sortilin-p75NTR (PMID:20036257)
• NTR2 and NTR3 were upregulated in prostate cancer cells with luminal phenotype (cytokeratin 18+) (PMID:20048080)
• There was a positive association between temporal cortex sortilin levels and severity of neuropathology. (PMID:20085800)
• A linear surface-exposed sequence, (163)RIFRSSDFAKNF(174), constitutes an important pro-NT binding epitope in sortilin. Systematic mutational analysis revealed residues Arg(163), Phe(165), Arg(166), and Phe(170) to be critical for the interaction. (PMID:20159974)
• Ciliary neurotrophic factor, and related ligands targeting the established CNTF receptor alpha, binds to sortilin with high affinity. (PMID:20584990)
• keratinocytes express sortilin mRNA, and the presence of sortilin protein is shown in cultured keratinocytes and in normal human skin (PMID:20613775)
• a single noncoding DNA variant at the chromosome 1p13 locus, rs12740374, influences LDL-C and myocardial infarction risk via liver-specific transcriptional regulation of the SORT1 gene by C/EBP transcription factors (PMID:20686566)
• Data show that sortilin, encoded by SORT1, is an intracellular sorting receptor for apolipoprotein (apo) B100, facilitates the formation and hepatic export of apoB100-containing lipoproteins, and regulates plasma low-density lipoprotein cholesterol. (PMID:20816088)
• identified significant association of a locus on chromosome 1p13.3 with plasma GRN levels through an unbiased genome-wide screening approach and implicated SORT1 as an important regulator of GRN levels (PMID:21087763)
• BACE1 retrograde trafficking is uniquely regulated by the cytoplasmic domain of sortilin. (PMID:21245145)
• Results suggest that proneurotrophin-3 and proBDNF may play important roles in the response to noise-induced injuries or ototoxic damage via the Sortilin:p75(NTR) death-signalling complex. (PMID:21261755)
• the impact of the SORT1 polymorphism on LDL cholesterol levels is age dependent (PMID:21466885)
• sortilin negatively regulates TGF-beta signaling by diverting trafficking of precursor proteins to the lysosome during transit through the biosynthetic pathway (PMID:21521695)
• the regulation of sortilin shedding and identify a novel mechanism by which sortilin ectodomain shedding acts as a regulatory switch for delivery of BDNF to the secretory pathway or to the lysosome, thus modulating the bioavailability of endogenous BDNF. (PMID:21730062)
• Sortilin, a protein acting as a neurotrophin transporter as well as a co-receptor for p75(NTR), was increased in the cytoplasm of primary and metastatic CRC cells, which suggests that sortilin could regulate neurotrophin transport in these cells. (PMID:21966426)
• the existence of an autocrine loop stimulated by proNGF and mediated by TrkA and sortilin, with the activation of Akt and Src, for the stimulation of breast cancer cell invasion. (PMID:22128158)
• It plays a roll in protein sorting and its dysfunction leads to life-style diseases. (review) (PMID:22256600)
• [review] The involvement of sortilin in neutrophin signaling in healthy and injured neurons is increasingly recognized as an important component in Alzheimer’s disease. (PMID:22297619)
• SORT1 mutations are not a common cause of familial ALS, and the influence of TARDBP mutations on SORT1 splicing still needs to be clarified. (PMID:22361451)
• Studies indicate that three loci for lipid levels identified by GWAS has identified functional genes GALNT2, TRIB1, and SORT1, and a functional variant at SORT1. (PMID:22418572)
• model in which increased hepatic sortilin binds intracellular APOB-containing particles in the Golgi apparatus as well as extracellular LDL at the plasma membrane and traffics them to the lysosome for degradation (PMID:22751103)
• Sortilin is a new alpha-Gal A receptor expressed in renal endothelial cells and that this receptor together with the M6PR is able to internalize circulating alpha-Gal A. (PMID:22768187)
• Lysosomal storage disorders are associated with deficiencies of alternative lysosomal receptors LIMPII and sortilin and/or of their cargos. (Review) (PMID:22884962)
• Even though sortilin binds and internalizes LDL by receptor-mediated endocytosis, mutations in the SORT1 gene are unlikely to cause autosomal dominant hypercholesterolemia and may only have a marginal effect on plasma LDL cholesterol levels. (PMID:23102784)
• A potential mechanism linking misregulation of sortilin splicing with altered PGRN metabolism, is proposed. (PMID:23236149)
• Together, our findings establish sortilin as a novel APP interaction partner that influences both production and cellular uptake of sAPP. (PMID:23283322)
• Genetic variants in SORT1 are associated with cognitive aging and appear to contribute differentially in men and women. (PMID:23318115)
• A significant association was observed between the SORT1 locus and low-density lipoproteins in male subjects. SORT1 is a valuable target for identifying individuals who would most benefit from early interventions to prevent cardiovascular disease. (PMID:23438231)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	sort1a	ENSDARG00000029402
danio_rerio	sort1b	ENSDARG00000056252
mus_musculus	Sort1	ENSMUSG00000068747
rattus_norvegicus	Sort1	ENSRNOG00000031814

Paralogs (4): SORCS1 (ENSG00000108018), SORL1 (ENSG00000137642), SORCS3 (ENSG00000156395), SORCS2 (ENSG00000184985)

Protein

Protein identifiers

Sortilin — Q99523 (reviewed: Q99523)

Alternative names: 100 kDa NT receptor, Glycoprotein 95, Neurotensin receptor 3

All UniProt accessions (5): A0A0J9YVU2, A0A0J9YVX1, A0A0J9YX61, A0A0J9YY30, Q99523

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Lysosomal proteins bind specifically to the receptor in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelysosomal compartment where the low pH mediates the dissociation of the complex. The receptor is then recycled back to the Golgi for another round of trafficking through its binding to the retromer. Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi.

Subunit / interactions. Interacts with LPL and SLC2A4. Interacts with the cytosolic adapter proteins GGA1 and GGA2. Interacts with numerous ligands including the receptor-associated protein LRPAP1/RAP, GM2A and NTS. Forms a complex with NGFR which binds specifically to the precursor forms of NGFB (proNGFB) and BDNF (proBDNF). Interacts with the Trk receptors NTRK1, NTRK2 and NTRK3; may regulate their anterograde axonal transport and signaling. Interacts with CLN5. Interacts with PSAP. Interacts with GRN; this interaction mediates endocytosis and lysosome delivery of progranulin; interaction occurs at the neuronal cell surface in a stressed nervous system. Interacts with the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35; which is involved in retrograde trafficking of the receptor from endosomes to the Golgi apparatus. Interacts with SMPD1; the interaction is required for SMPD1 targeting to lysosomes.

Subcellular location. Golgi apparatus. Golgi stack membrane. Endosome membrane. Endoplasmic reticulum membrane. Nucleus membrane. Cell membrane. Lysosome membrane.

Tissue specificity. Expressed in brain and prostate (at protein level). Expressed at high levels in brain, spinal cord, heart, skeletal muscle, thyroid, placenta and testis. Expressed at lower levels in lymphoid organs, kidney, colon and liver.

Post-translational modifications. The N-terminal propeptide is cleaved by furin and possibly other homologous proteases. Palmitoylated. Undergoes cysteine S-palmitoylation which promotes the partitioning of the receptor into an endosomal membrane subdomain where it can interact with the retromer cargo-selective complex which mediates its retrograde trafficking to the Golgi apparatus. Phosphorylation at Ser-825 facilitates the interaction with GGA1.

Disease relevance. A common polymorphism located in a non-coding region between CELSR2 and PSRC1 alters a CEBP transcription factor binding site and is responsible for changes in hepatic expression of SORT1. Altered SORT1 expression in liver affects low density lipoprotein cholesterol levels in plasma and is associated with susceptibility to myocardial infarction.

Domain organisation. The N-terminal propeptide may facilitate precursor transport within the Golgi stack. Intrachain binding of the N-terminal propeptide and the extracellular domain may also inhibit premature ligand binding. The extracellular domain may be shed following protease cleavage in some cell types.

Induction. During osteoblast differentiation.

Polymorphism. Genetic variations in SORT1 influence low density lipoprotein cholesterol (LDL-C) variability and contribute to the low density lipoprotein cholesterol level quantitative trait locus 6 (LDLCQ6) [MIM:613589].

Similarity. Belongs to the VPS10-related sortilin family. SORT1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99523-1	1	yes
Q99523-2	2

RefSeq proteins (2): NP_001192157, NP_002950* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006581	VPS10	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR031777	Sortilin_C	Domain
IPR031778	Sortilin_N	Domain
IPR050310	VPS10-sortilin	Family

Pfam: PF15901, PF15902

UniProt features (136 total): strand 58, helix 15, mutagenesis site 10, repeat 9, disulfide bond 8, turn 7, region of interest 6, glycosylation site 6, modified residue 3, short sequence motif 2, topological domain 2, splice variant 2, signal peptide 1, propeptide 1, chain 1, lipid moiety-binding region 1, transmembrane region 1, sequence variant 1, sequence conflict 1, domain 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
3F6K	X-RAY DIFFRACTION	2
5MRI	X-RAY DIFFRACTION	2
3G2V	X-RAY DIFFRACTION	2.1
3G2U	X-RAY DIFFRACTION	2.3
5MRH	X-RAY DIFFRACTION	2.5
4PO7	X-RAY DIFFRACTION	2.66
4MSL	X-RAY DIFFRACTION	2.7
4N7E	X-RAY DIFFRACTION	2.7
6X3L	X-RAY DIFFRACTION	2.7
9R18	X-RAY DIFFRACTION	2.8
8T8R	X-RAY DIFFRACTION	2.87
6X48	X-RAY DIFFRACTION	2.9
6X4H	X-RAY DIFFRACTION	2.9
8T8S	X-RAY DIFFRACTION	2.99
9I0N	ELECTRON MICROSCOPY	3.1
9I0O	ELECTRON MICROSCOPY	3.36
6EHO	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99523-F1	83.27	0.66

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 (4): 814, 819, 825, 783

Disulfide bonds (8): 86–556, 257–277, 448–458, 612–651, 634–666, 668–723, 675–688, 702–740

Glycosylation sites (6): 98, 162, 274, 406, 582, 684

Mutagenesis-validated functional residues (10):

Position	Phenotype
74–77	abrogates propeptide cleavage.
76–77	abrogates propeptide cleavage.
783	loss of palmitoylation. decreased recycling from endosomes to the golgi apparatus. increased lysosomal degradation.
792	reduces endocytosis and golgi to endosome sorting; when associated with a-795.
795	reduces endocytosis and golgi to endosome sorting; when associated with a-792.
823–824	reduces interaction with gga1.
825	reduces interaction with gga1.
826–828	abrogates interaction with gga1 and impairs localization to the golgi.
829–830	abrogates interaction with gga1 and impairs localization to the golgi.
829–830	abrogates interaction with gga2. reduces endocytosis and golgi to endosome sorting; when associated with a-792 and a-795

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-432722	Golgi Associated Vesicle Biogenesis
R-HSA-199991	Membrane Trafficking
R-HSA-199992	trans-Golgi Network Vesicle Budding
R-HSA-5653656	Vesicle-mediated transport

MSigDB gene sets: 411 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, ELVIDGE_HYPOXIA_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, MODULE_451, MYOGENIN_Q6, GOBP_LYSOSOMAL_TRANSPORT, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOCC_VACUOLAR_MEMBRANE, GOBP_NEGATIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_VESICLE_ORGANIZATION, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, GOBP_PROTEIN_TARGETING

GO Biological Process (21): ossification (GO:0001503), protein targeting to lysosome (GO:0006622), Golgi to endosome transport (GO:0006895), endocytosis (GO:0006897), G protein-coupled receptor signaling pathway (GO:0007186), neuropeptide signaling pathway (GO:0007218), endosome to lysosome transport (GO:0008333), extrinsic apoptotic signaling pathway via death domain receptors (GO:0008625), regulation of gene expression (GO:0010468), myotube differentiation (GO:0014902), vesicle organization (GO:0016050), endosome transport via multivesicular body sorting pathway (GO:0032509), response to insulin (GO:0032868), negative regulation of fat cell differentiation (GO:0045599), obsolete D-glucose import (GO:0046323), neurotrophin TRK receptor signaling pathway (GO:0048011), plasma membrane to endosome transport (GO:0048227), Golgi to lysosome transport (GO:0090160), maintenance of synapse structure (GO:0099558), cell differentiation (GO:0030154), nerve growth factor signaling pathway (GO:0038180)

GO Molecular Function (6): nerve growth factor receptor activity (GO:0010465), enzyme binding (GO:0019899), neurotensin receptor activity, non-G protein-coupled (GO:0030379), nerve growth factor binding (GO:0048406), retromer complex binding (GO:1905394), protein binding (GO:0005515)

GO Cellular Component (22): lysosome (GO:0005764), lysosomal membrane (GO:0005765), early endosome (GO:0005769), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), cell surface (GO:0009986), endosome membrane (GO:0010008), membrane (GO:0016020), clathrin-coated vesicle (GO:0030136), trans-Golgi network transport vesicle (GO:0030140), cytoplasmic vesicle (GO:0031410), nuclear membrane (GO:0031965), Golgi cisterna membrane (GO:0032580), perinuclear region of cytoplasm (GO:0048471), cerebellar climbing fiber to Purkinje cell synapse (GO:0150053), nucleus (GO:0005634), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), cytoplasmic vesicle membrane (GO:0030659)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
trans-Golgi Network Vesicle Budding	1
Vesicle-mediated transport	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
cellular anatomical structure	4
lysosomal transport	3
vesicle-mediated transport	3
organelle membrane	3
endomembrane system	3
intercellular transport	2
cytosolic transport	2
endosome	2
intracellular membrane-bounded organelle	2
membrane	2
multicellular organismal process	1
protein targeting to vacuole	1
protein localization to lysosome	1
post-Golgi vesicle-mediated transport	1
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
G protein-coupled receptor activity	1
signal transduction	1
G protein-coupled receptor signaling pathway	1
extrinsic apoptotic signaling pathway	1
gene expression	1
regulation of macromolecule biosynthetic process	1
striated muscle cell differentiation	1
organelle organization	1
endosomal transport	1
multivesicular body sorting pathway	1
response to peptide hormone	1
fat cell differentiation	1
negative regulation of cell differentiation	1
regulation of fat cell differentiation	1
cell surface receptor protein tyrosine kinase signaling pathway	1
neurotrophin signaling pathway	1
Golgi to vacuole transport	1
cell junction maintenance	1
synapse organization	1
cellular developmental process	1
neurotrophin receptor activity	1
nerve growth factor signaling pathway	1

Protein interactions and networks

STRING

2066 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SORT1	NGFR	P08138	997
SORT1	BDNF	P23560	995
SORT1	NTS	P30990	991
SORT1	NGF	P01138	990
SORT1	PSRC1	Q6PGN9	954
SORT1	CELSR2	Q9HCU4	947
SORT1	GRN	P23781	940
SORT1	NTF4	P34130	883
SORT1	NTRK2	Q16620	882
SORT1	PCSK9	Q8NBP7	867
SORT1	NTF3	P20783	851
SORT1	APOB	P04114	845
SORT1	NTRK3	Q16288	842
SORT1	NTRK1	P04629	835
SORT1	APP	P05067	798

IntAct

193 interactions, top by confidence:

A	B	Type	Score
SORT1	LRPAP1	psi-mi:“MI:0407”(direct interaction)	0.810
SORT1	NTS	psi-mi:“MI:0915”(physical association)	0.700
GGA2	SORT1	psi-mi:“MI:0915”(physical association)	0.700
SORT1	GGA2	psi-mi:“MI:0407”(direct interaction)	0.700
SORT1	NGF	psi-mi:“MI:0407”(direct interaction)	0.680
SORT1	SORT1	psi-mi:“MI:0407”(direct interaction)	0.680
SORT1	NGF	psi-mi:“MI:0915”(physical association)	0.680
GGA1	SORT1	psi-mi:“MI:0407”(direct interaction)	0.670
NHLRC2	CEP76	psi-mi:“MI:0914”(association)	0.670
SORT1	GGA1	psi-mi:“MI:0915”(physical association)	0.670
SORT1	GGA1	psi-mi:“MI:0407”(direct interaction)	0.670
SORT1	LPL	psi-mi:“MI:0407”(direct interaction)	0.660
LPL	SORT1	psi-mi:“MI:0914”(association)	0.660
SORT1	LPL	psi-mi:“MI:0915”(physical association)	0.660
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
GRN	SORT1	psi-mi:“MI:0915”(physical association)	0.610
SORT1	NTS	psi-mi:“MI:0915”(physical association)	0.610
SORT1	GRN	psi-mi:“MI:0407”(direct interaction)	0.610
SORT1	GLA	psi-mi:“MI:0407”(direct interaction)	0.590
SORT1	GLA	psi-mi:“MI:0915”(physical association)	0.590

BioGRID (255): SORT1 (Affinity Capture-MS), APBB2 (Affinity Capture-MS), XIAP (Affinity Capture-MS), ASS1 (Affinity Capture-MS), BAD (Affinity Capture-MS), BLMH (Affinity Capture-MS), CDK1 (Affinity Capture-MS), CDK2 (Affinity Capture-MS), COPA (Affinity Capture-MS), CSNK1G2 (Affinity Capture-MS), CSPG4 (Affinity Capture-MS), PHC2 (Affinity Capture-MS), EIF2B1 (Affinity Capture-MS), GOLGA3 (Affinity Capture-MS), HP (Affinity Capture-MS)

ESM2 similar proteins: A1C8D8, A1DAY6, A2QHH4, A4RF05, A5E1P1, A6QWZ2, A6ZKT1, A8PE82, B0E2U2, B0YA89, B2WDP9, B3LNF5, B5VDW2, B6H711, B6QMS8, B8MG72, B8NX76, C0NKP8, C0S7J1, C1FZI7, C1GTA5, C4JI06, C5DU19, C5FYX2, C5GVC6, C5JC96, C5P311, C6HAY7, C7GX93, C7YGZ0, C8Z3X9, C9SM62, D1Z9Q3, D4AQV3, D4D4B1, E3QER5, E3RE00, E4UV76, E4ZVX1, O54861

Diamond homologs: O54861, Q6NUT7, Q6PHU5, Q98930, Q99523, Q92673, Q95209

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
PAK2	“down-regulates activity”	SORT1	phosphorylation
PAK1	“down-regulates activity”	SORT1	phosphorylation
PAK3	“down-regulates activity”	SORT1	phosphorylation
“AP-1 complex”	“up-regulates quantity”	SORT1	binding
CSNK2B	“up-regulates quantity by stabilization”	SORT1	phosphorylation
SORT1	“up-regulates quantity”	APOE	binding
SORT1	“up-regulates quantity”	APOA1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 156 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
IL-6-type cytokine receptor ligand interactions	6	36.6×	5e-06
R-HSA-425366	7	12.2×	5e-04
SLC-mediated transmembrane transport	9	5.1×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	6	30.8×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	10
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

3744 predictions. Top by Δscore:

Variant	Effect	Δscore
1:109313899:AGGT:A	donor_gain	1.0000
1:109313902:T:TA	donor_gain	1.0000
1:109313962:ATTT:A	donor_gain	1.0000
1:109313965:T:TA	donor_gain	1.0000
1:109314256:CTCA:C	donor_loss	1.0000
1:109314257:TCA:T	donor_loss	1.0000
1:109314258:CAC:C	donor_loss	1.0000
1:109314259:A:AG	donor_loss	1.0000
1:109314381:GAACC:G	acceptor_loss	1.0000
1:109314382:AACCT:A	acceptor_loss	1.0000
1:109314383:ACC:A	acceptor_loss	1.0000
1:109314384:CCTGT:C	acceptor_loss	1.0000
1:109314385:C:CA	acceptor_loss	1.0000
1:109314780:T:C	acceptor_gain	1.0000
1:109314788:T:C	acceptor_gain	1.0000
1:109314788:T:TC	acceptor_gain	1.0000
1:109317970:C:CC	acceptor_gain	1.0000
1:109322941:T:TA	donor_gain	1.0000
1:109322944:T:TA	donor_gain	1.0000
1:109324898:CAGTT:C	donor_gain	1.0000
1:109326990:A:AC	donor_gain	1.0000
1:109326991:C:CC	donor_gain	1.0000
1:109326994:A:AC	donor_gain	1.0000
1:109326994:AAT:A	donor_gain	1.0000
1:109327024:AATGG:A	donor_gain	1.0000
1:109327597:CTGCA:C	acceptor_gain	1.0000
1:109327598:TGCA:T	acceptor_gain	1.0000
1:109327599:GCA:G	acceptor_gain	1.0000
1:109327600:CA:C	acceptor_gain	1.0000
1:109327600:CAC:C	acceptor_gain	1.0000

AlphaMissense

5449 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:109316953:C:G	R716P	1.000
1:109323004:C:G	C651S	1.000
1:109323005:A:T	C651S	1.000
1:109327092:A:G	W515R	1.000
1:109327092:A:T	W515R	1.000
1:109336300:C:A	W437C	1.000
1:109336300:C:G	W437C	1.000
1:109336302:A:G	W437R	1.000
1:109336302:A:T	W437R	1.000
1:109342072:G:C	F350L	1.000
1:109342072:G:T	F350L	1.000
1:109342074:A:G	F350L	1.000
1:109342111:C:A	W337C	1.000
1:109342111:C:G	W337C	1.000
1:109342113:A:G	W337R	1.000
1:109342113:A:T	W337R	1.000
1:109342134:A:G	S330P	1.000
1:109316932:C:G	C723S	0.999
1:109316933:A:T	C723S	0.999
1:109317931:C:G	C688S	0.999
1:109317932:A:G	C688R	0.999
1:109317932:A:T	C688S	0.999
1:109322932:C:G	C675S	0.999
1:109322932:C:T	C675Y	0.999
1:109322933:A:G	C675R	0.999
1:109322933:A:T	C675S	0.999
1:109323003:A:C	C651W	0.999
1:109323005:A:G	C651R	0.999
1:109323096:C:A	W620C	0.999
1:109323096:C:G	W620C	0.999

dbSNP variants (sampled 300 via entrez): RS1000022847 (1:109361699 C>A,G), RS1000059151 (1:109313680 A>C,T), RS1000078040 (1:109355387 C>A,T), RS1000115090 (1:109323635 G>A), RS1000246977 (1:109373285 C>T), RS1000278053 (1:109379421 C>G,T), RS1000281802 (1:109342724 C>G), RS1000299543 (1:109373146 C>T), RS1000343259 (1:109317946 T>C), RS1000348011 (1:109313908 T>C), RS1000412589 (1:109336643 A>G), RS1000439258 (1:109386449 T>C), RS1000474409 (1:109361364 C>T), RS1000497905 (1:109349893 G>A,C), RS1000608160 (1:109336710 G>A)

Disease associations

OMIM: gene MIM:602458 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

44 associations (top):

Study	Trait	p-value
GCST000132_7	LDL cholesterol	6.000000e-33
GCST000134_1	LDL cholesterol	3.000000e-29
GCST000283_1	LDL cholesterol	2.000000e-12
GCST000287_7	LDL cholesterol	2.000000e-42
GCST000340_7	Myocardial infarction (early onset)	8.000000e-12
GCST000635_10	Response to statin therapy	4.000000e-06
GCST000649_1	Chronic kidney disease	1.000000e-07
GCST000759_23	LDL cholesterol	1.000000e-170
GCST000760_5	Cholesterol, total	6.000000e-131
GCST000911_1	Progranulin levels	2.000000e-30
GCST000945_2	Coronary artery disease	8.000000e-11
GCST000975_10	LDL cholesterol	9.000000e-29
GCST000998_1	Coronary heart disease	3.000000e-10
GCST000999_17	Coronary heart disease	6.000000e-10
GCST001233_13	Metabolite levels	2.000000e-19
GCST001727_9	Lipoprotein-associated phospholipase A2 activity and mass	2.000000e-22
GCST002221_36	Cholesterol, total	2.000000e-170
GCST002222_48	LDL cholesterol	5.000000e-241
GCST002287_2	Coronary artery disease or ischemic stroke	1.000000e-08
GCST002289_6	Coronary artery disease	1.000000e-08
GCST002290_7	Coronary artery disease or large artery stroke	8.000000e-17
GCST002896_36	Cholesterol, total	2.000000e-64
GCST002898_33	LDL cholesterol	2.000000e-91
GCST002899_31	HDL cholesterol	2.000000e-09
GCST003116_15	Coronary artery disease	2.000000e-23
GCST003117_35	Myocardial infarction	1.000000e-15
GCST003877_1	Abdominal aortic aneurysm	7.000000e-09
GCST004231_2	Total cholesterol levels	2.000000e-17
GCST004233_1	LDL cholesterol levels	4.000000e-289
GCST004233_42	LDL cholesterol levels	2.000000e-31

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004625	progranulin measurement
EFO:0004746	lipoprotein-associated phospholipase A(2) measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004337	intelligence
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0007804	LDL cholesterol change measurement
EFO:0008343	sex interaction measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3091 (SINGLE PROTEIN), CHEMBL4680051 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 235 (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
CHEMBL506981	REMINERTANT	3	235

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — Sortilin family proteins

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
A3-PGRNC15*	Antagonist	9.73	pKd

Binding affinities (BindingDB)

57 measured of 57 human assays (57 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[(2-methylpyrimidin-4-yl)carbamoyl]-5-(trifluoromethyl)benzoic acid	IC50	88 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
2-[(5,6-dimethyl-2-pyridinyl)carbamoyl]-5-(trifluoromethyl)benzoic acid	IC50	170 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
2-[(6-methyl-2-pyridinyl)carbamoyl]-5-propan-2-ylbenzoic acid	IC50	200 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
2-[(5,6-dimethylpyrazin-2-yl)carbamoyl]-5-(trifluoromethyl)benzoic acid	IC50	240 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
(2S)-5,5-dimethyl-2-[(morpholine-4-carbonyl)amino]hexanoic acid	IC50	260 nM	US-20250161321: AMINO ACID BASED CARBAMATES AND/OR UREAS FOR THE TREATMENT OF SORTILIN DEPENDENT DISEASES
2-[(6-methyl-2-pyridinyl)carbamoyl]-5-prop-1-en-2-ylbenzoic acid	IC50	300 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
2-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl]carbamoyl]-5-(trifluoromethyl)benzoic acid	IC50	360 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
2-[(4-methylpyrimidin-2-yl)carbamoyl]-5-(trifluoromethyl)benzoic acid	IC50	360 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
(2S)-5,5-dimethyl-2-[(1,4-oxazepane-4-carbonyl)amino]hexanoic acid	IC50	370 nM	US-20250161321: AMINO ACID BASED CARBAMATES AND/OR UREAS FOR THE TREATMENT OF SORTILIN DEPENDENT DISEASES
(2S)-2-[(benzylcarbamoyl)amino]-5,5-dimethylhexanoic acid	IC50	380 nM	US-20250161321: AMINO ACID BASED CARBAMATES AND/OR UREAS FOR THE TREATMENT OF SORTILIN DEPENDENT DISEASES
(2S)-2-{[benzyl(methyl)carbamoyl]amino}-5,5-dimethylhexanoic acid	IC50	430 nM	US-20250161321: AMINO ACID BASED CARBAMATES AND/OR UREAS FOR THE TREATMENT OF SORTILIN DEPENDENT DISEASES
4,5-dichloro-2-[(5,6-dimethyl-2-pyridinyl)carbamoyl]benzoic acid	IC50	480 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
4,5-dichloro-2-[(2-methylpyrimidin-4-yl)carbamoyl]benzoic acid	IC50	480 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
5-bromo-2-[(6-methylpyridazin-3-yl)carbamoyl]benzoic acid	IC50	490 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
(2S)-2-{[(benzyloxy)carbonyl]amino}-5,5-dimethylhexanoic acid	IC50	560 nM	US-20250161321: AMINO ACID BASED CARBAMATES AND/OR UREAS FOR THE TREATMENT OF SORTILIN DEPENDENT DISEASES
5-bromo-2-[(5,6-dimethyl-2-pyridinyl)carbamoyl]benzoic acid	IC50	570 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
2-[(2-methylpyrimidin-4-yl)carbamoyl]-4,5-bis(trifluoromethyl)benzoic acid	KI	599 nM	US-9682967: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
2-[(2,6-dimethyl-4-pyridinyl)carbamoyl]-5-(trifluoromethyl)benzoic acid	KI	614 nM	US-9682967: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
2-(5,6,7,8-tetrahydroquinolin-2-ylcarbamoyl)-4,5-bis(trifluoromethyl)benzoic acid	IC50	620 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
2-[(5,6-dimethyl-2-pyridinyl)carbamoyl]-4,5-bis(trifluoromethyl)benzoic acid	IC50	640 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
2-[(2-methyl-4-pyridinyl)carbamoyl]-5-(trifluoromethyl)benzoic acid	IC50	700 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
2-[(6-methyl-2-pyridinyl)carbamoyl]-4,5-bis(trifluoromethyl)benzoic acid	IC50	750 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
5-bromo-2-[(2-methylpyrimidin-4-yl)carbamoyl]benzoic acid	IC50	750 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
2-(5,6,7,8-tetrahydroquinolin-2-ylcarbamoyl)-5-(trifluoromethyl)benzoic acid	IC50	760 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
4,5-dichloro-2-[(6-methyl-2-pyridinyl)carbamoyl]benzoic acid	IC50	830 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
5-Bromo-N-(6-methyl-pyridin-3-yl)-phthalamic acid	IC50	970 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
5-bromo-2-[(5-chloro-2-pyridinyl)carbamoyl]benzoic acid	IC50	990 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
2-[(4-methyl-2-pyridinyl)carbamoyl]-5-(trifluoromethyl)benzoic acid	IC50	1000 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
2-[(6-methyl-2-pyridinyl)carbamoyl]-5-propylbenzoic acid	IC50	1100 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
2-[(4,5-dimethylpyrimidin-2-yl)carbamoyl]-5-(trifluoromethyl)benzoic acid	IC50	1200 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
5-bromo-2-[(6-methyl-2-pyridinyl)carbamoyl]benzoic acid	IC50	1200 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
5-bromo-2-[(4-methyl-1,3-thiazol-2-yl)carbamoyl]benzoic acid	IC50	1300 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
5-bromo-2-[(6-methylpyrimidin-4-yl)carbamoyl]benzoic acid	IC50	1300 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
5-chloro-2-[(6-methyl-2-pyridinyl)carbamoyl]benzoic acid	IC50	1400 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
2-[(2-methoxy-4-pyridinyl)carbamoyl]-5-(trifluoromethyl)benzoic acid	IC50	1600 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
5-bromo-2-[(6-chloro-2-pyridinyl)carbamoyl]benzoic acid	IC50	1600 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
5-bromo-2-[(5-methyl-2-pyridinyl)carbamoyl]benzoic acid	IC50	1700 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
4,5-dichloro-2-[(2-methyl-4-pyridinyl)carbamoyl]benzoic acid	IC50	1800 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
5-bromo-2-[(2-methyl-4-pyridinyl)carbamoyl]benzoic acid	IC50	1800 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
2-[(6-methyl-2-pyridinyl)carbamoyl]-5-(trifluoromethyl)benzoic acid	IC50	1800 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
5-bromo-2-[(4,6-dimethyl-2-pyridinyl)carbamoyl]benzoic acid	IC50	2000 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
5-bromo-2-(quinolin-2-ylcarbamoyl)benzoic acid	IC50	2100 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
4,5-dichloro-2-[(4-methyl-2-pyridinyl)carbamoyl]benzoic acid	IC50	2200 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
5-bromo-2-[(4-methyl-2-pyridinyl)carbamoyl]benzoic acid	IC50	2400 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
5-bromo-2-[(5,6-dichloro-2-pyridinyl)carbamoyl]benzoic acid	IC50	3200 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
4,5-dimethyl-2-[(6-methyl-2-pyridinyl)carbamoyl]benzoic acid	IC50	3400 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
2-(pyridin-4-ylmethylcarbamoyl)-5-(trifluoromethyl)benzoic acid	IC50	3600 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
5-Bromo-N-(3-methyl-pyridin-2-yl)-phthalamic acid	IC50	3600 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
5-bromo-2-(pyridin-2-ylcarbamoyl)benzoic acid	IC50	3600 nM	US-10195186: N-substituted-5-substituted phthalamic acids as sortilin inhibitors
5-bromo-2-[(3-cyano-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)carbamoyl]benzoic acid	IC50	4000 nM	US-9682967: N-substituted-5-substituted phthalamic acids as sortilin inhibitors

ChEMBL bioactivities

268 potent at pChembl≥5 of 290 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Kd	1	nM	CHEMBL5574034
7.70	IC50	20	nM	CHEMBL4752312
7.19	IC50	65	nM	CHEMBL4751985
7.08	Ki	84	nM	CHEMBL3098768
7.08	Ki	84	nM	CHEMBL6032515
7.06	IC50	88	nM	CHEMBL3098768
7.06	IC50	88	nM	CHEMBL6032515
7.05	IC50	90	nM	CHEMBL4751566
7.00	IC50	100	nM	CHEMBL3098768
6.92	IC50	120	nM	CHEMBL4752312
6.79	Ki	162	nM	CHEMBL3098767
6.77	IC50	170	nM	CHEMBL3098767
6.77	IC50	170	nM	CHEMBL4741088
6.72	Ki	190	nM	CHEMBL5961903
6.72	Ki	190	nM	CHEMBL3098744
6.70	IC50	200	nM	CHEMBL5961903
6.70	IC50	200	nM	CHEMBL3098744
6.64	Ki	229	nM	CHEMBL5758095
6.62	IC50	238	nM	REMINERTANT
6.62	IC50	240	nM	CHEMBL5758095
6.58	IC50	260	nM	CHEMBL3098745
6.54	IC50	290	nM	CHEMBL4751566
6.54	Ki	286	nM	CHEMBL6032515
6.54	Ki	286	nM	CHEMBL5758927
6.52	IC50	300	nM	CHEMBL6032515
6.52	IC50	300	nM	CHEMBL5758927
6.50	IC50	316.2	nM	CHEMBL3098745
6.48	IC50	330	nM	CHEMBL3098745
6.46	IC50	350	nM	CHEMBL4759392
6.46	Ki	343	nM	CHEMBL5856133
6.46	Ki	343	nM	CHEMBL6014673
6.44	IC50	360	nM	NEUROTENSIN
6.44	IC50	360	nM	CHEMBL5856133
6.44	IC50	360	nM	CHEMBL6014673
6.42	IC50	380	nM	CHEMBL1852155
6.40	IC50	400	nM	CHEMBL133849
6.37	Ki	429	nM	CHEMBL3098745
6.36	IC50	440	nM	CHEMBL439494
6.35	IC50	450	nM	CHEMBL3098745
6.34	Ki	457	nM	CHEMBL5855899
6.34	Ki	457	nM	CHEMBL5965454
6.33	Ki	467	nM	CHEMBL3098765
6.33	Ki	467	nM	CHEMBL5804280
6.32	IC50	480	nM	CHEMBL5855899
6.32	IC50	480	nM	CHEMBL5965454
6.32	IC50	480	nM	CHEMBL336836
6.32	IC50	480	nM	CHEMBL133378
6.31	IC50	490	nM	CHEMBL3098765
6.31	IC50	490	nM	CHEMBL4791749
6.31	IC50	490	nM	CHEMBL5804280

PubChem BioAssay actives

77 with measured affinity, of 145 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-2-[[6-[3-[2-[2-[2-[2-[2-[2-[[5-[1-[(2-cyano-3-pyridinyl)methyl]-2,2-dimethyl-3-oxopyrrolo[2,3-b]pyridin-6-yl]pyrimidin-2-yl]amino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylcarbamoyl]phenoxy]pyridine-3-carbonyl]amino]-5,5-dimethylhexanoic acid	2094835: Binding affinity to 6-His tagged sortilin (unknown origin) assessed as equilibrium dissociation constant by MST analysis	kd	0.0010	uM
(2S)-2-[[6-[3-[[10-[[2-[(2R)-4-[5-[1-[(2-cyano-3-pyridinyl)methyl]-2,2-dimethyl-3-oxopyrrolo[2,3-b]pyridin-6-yl]pyrimidin-2-yl]-2-methylpiperazin-1-yl]-2-oxoethyl]amino]-10-oxodecyl]carbamoyl]phenoxy]pyridine-3-carbonyl]amino]-5,5-dimethylhexanoic acid	2094835: Binding affinity to 6-His tagged sortilin (unknown origin) assessed as equilibrium dissociation constant by MST analysis	kd	0.0010	uM
(2S)-2-[[6-[3-[2-[2-[2-[2-[2-[2-[5-[1-[(2-cyano-3-pyridinyl)methyl]-2,2-dimethyl-3-oxopyrrolo[2,3-b]pyridin-6-yl]pyrimidin-2-yl]oxyethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylcarbamoyl]phenoxy]pyridine-3-carbonyl]amino]-5,5-dimethylhexanoic acid	2094835: Binding affinity to 6-His tagged sortilin (unknown origin) assessed as equilibrium dissociation constant by MST analysis	kd	0.0010	uM
(2S)-2-[[6-[3-[2-[2-[2-[2-[2-[2-[2-[4-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]butanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]phenoxy]pyridine-3-carbonyl]amino]-5,5-dimethylhexanoic acid	2094835: Binding affinity to 6-His tagged sortilin (unknown origin) assessed as equilibrium dissociation constant by MST analysis	kd	0.0010	uM
(2S)-2-[[6-[3-[8-[2-[(2R)-4-[5-[1-[(2-cyano-3-pyridinyl)methyl]-2,2-dimethyl-3-oxopyrrolo[2,3-b]pyridin-6-yl]pyrimidin-2-yl]-2-methylpiperazin-1-yl]-2-oxoethoxy]octylcarbamoyl]phenoxy]pyridine-3-carbonyl]amino]-5,5-dimethylhexanoic acid	2094835: Binding affinity to 6-His tagged sortilin (unknown origin) assessed as equilibrium dissociation constant by MST analysis	kd	0.0010	uM
(2S)-2-[[6-[3-[4-[2-[(2R)-4-[5-[1-[(2-cyano-3-pyridinyl)methyl]-2,2-dimethyl-3-oxopyrrolo[2,3-b]pyridin-6-yl]pyrimidin-2-yl]-2-methylpiperazin-1-yl]-2-oxoethoxy]butylcarbamoyl]phenoxy]pyridine-3-carbonyl]amino]-5,5-dimethylhexanoic acid	2094835: Binding affinity to 6-His tagged sortilin (unknown origin) assessed as equilibrium dissociation constant by MST analysis	kd	0.0010	uM
(2S)-5,5-dimethyl-2-[(6-phenoxypyridine-3-carbonyl)amino]hexanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	0.0200	uM
(2S)-4,4-dimethyl-2-[(6-phenoxypyridine-3-carbonyl)amino]pentanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	0.0650	uM
(2S)-2-[(4-chloro-1H-pyrrole-2-carbonyl)amino]-5,5-dimethylhexanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	0.0900	uM
2-(5,6,7,8-tetrahydroquinolin-2-ylcarbamoyl)-5-(trifluoromethyl)benzoic acid	1061998: Displacement of [3H]-neurotensin from sortilin (unknown origin) incubated 30 mins prior to [3H]-neurotensin addition measured after 6 hrs by scintillation proximity assay	ic50	0.1000	uM
(2S)-2-[(3,5-dichlorobenzoyl)amino]-5,5-dimethylhexanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	0.1700	uM
2-[(5,6-dimethyl-2-pyridinyl)carbamoyl]-5-(trifluoromethyl)benzoic acid	1061998: Displacement of [3H]-neurotensin from sortilin (unknown origin) incubated 30 mins prior to [3H]-neurotensin addition measured after 6 hrs by scintillation proximity assay	ic50	0.1700	uM
2-[[1-(7-chloroquinolin-4-yl)-5-(2,6-dimethoxyphenyl)pyrazole-3-carbonyl]amino]adamantane-2-carboxylic acid	757771: Binding affinity to NTR3 (unknown origin)	ic50	0.2380	uM
2-[(6-methyl-2-pyridinyl)carbamoyl]-5-(trifluoromethyl)benzoic acid	1475127: Displacement of [3H]-neurotensin from human His6-tagged sortilin pretreated for 30 mins followed by [3H]-neurotensin addition after 6 hrs measured for 360 secs by SPA	ic50	0.3162	uM
(2S)-2-[(3,5-dichlorobenzoyl)amino]-4,4-dimethylpentanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	0.3500	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-4-amino-2-[[(2S)-4-carboxy-2-[[(2S)-3-(4-hydroxyphenyl)-2-[[(2S)-4-methyl-2-[[(2S)-5-oxopyrrolidine-2-carbonyl]amino]pentanoyl]amino]propanoyl]amino]butanoyl]amino]-4-oxobutanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	1061981: Displacement of [3H]-neurotensin from human sortilin incubated 30 mins prior to [3H]-neurotensin addition measured after 6 hrs by scintillation proximity assay	ic50	0.3600	uM
9-benzyl-3-methylidene-1,5-bis-(4-methylphenyl)sulfonyl-1,5,9-triazacyclododecane	1668003: Inhibition of GFP-tagged Sortilin (unknown origin) expressed in HEK293T cells after 42 hrs by FACS analysis	ic50	0.3800	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-7-(methylamino)heptanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147067: Evaluated for binding affinity by inhibiting binding of [125I]Tyr(3)-NT to human Neurotensin receptor 3	ic50	0.4000	uM
(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-4-amino-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-carboxybutanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-4-oxobutanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoic acid	147067: Evaluated for binding affinity by inhibiting binding of [125I]Tyr(3)-NT to human Neurotensin receptor 3	ic50	0.4400	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-5-[[amino(ethylamino)methylidene]amino]pentanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147067: Evaluated for binding affinity by inhibiting binding of [125I]Tyr(3)-NT to human Neurotensin receptor 3	ic50	0.4800	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-5-(dimethylamino)pentanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147067: Evaluated for binding affinity by inhibiting binding of [125I]Tyr(3)-NT to human Neurotensin receptor 3	ic50	0.4800	uM
3-tert-butyl-1-[(5-phenyl-1,3,4-oxadiazol-2-yl)methyl]pyrazole-5-carboxylic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	0.4900	uM
5-bromo-2-[(2-methylpyrimidin-4-yl)carbamoyl]benzoic acid	1061998: Displacement of [3H]-neurotensin from sortilin (unknown origin) incubated 30 mins prior to [3H]-neurotensin addition measured after 6 hrs by scintillation proximity assay	ic50	0.4900	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-5-(imidazolidin-2-ylamino)pentanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147067: Evaluated for binding affinity by inhibiting binding of [125I]Tyr(3)-NT to human Neurotensin receptor 3	ic50	0.5100	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2,6-diaminohexanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147067: Evaluated for binding affinity by inhibiting binding of [125I]Tyr(3)-NT to human Neurotensin receptor 3	ic50	0.5120	uM
[(6S)-6-amino-7-[[N’-[(4S)-4-amino-5-[(2S)-2-[[(2S)-1-[[(2S,3S)-1-[[(1S)-1-carboxy-3-methylbutyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-5-oxopentyl]carbamimidoyl]amino]-7-oxoheptyl]-trimethylazanium	147067: Evaluated for binding affinity by inhibiting binding of [125I]Tyr(3)-NT to human Neurotensin receptor 3	ic50	0.5500	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-5-(2-amino-4,5-dihydroimidazol-1-yl)pentanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147067: Evaluated for binding affinity by inhibiting binding of [125I]Tyr(3)-NT to human Neurotensin receptor 3	ic50	0.5900	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-5-(methylamino)pentanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147067: Evaluated for binding affinity by inhibiting binding of [125I]Tyr(3)-NT to human Neurotensin receptor 3	ic50	0.6400	uM
(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147067: Evaluated for binding affinity by inhibiting binding of [125I]Tyr(3)-NT to human Neurotensin receptor 3	ic50	0.6400	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-7-(dimethylamino)heptanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147067: Evaluated for binding affinity by inhibiting binding of [125I]Tyr(3)-NT to human Neurotensin receptor 3	ic50	0.7000	uM
5-bromo-2-[(6-methyl-2-pyridinyl)carbamoyl]benzoic acid	1061998: Displacement of [3H]-neurotensin from sortilin (unknown origin) incubated 30 mins prior to [3H]-neurotensin addition measured after 6 hrs by scintillation proximity assay	ic50	0.7100	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-5-[(N’-methylcarbamimidoyl)amino]pentanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147067: Evaluated for binding affinity by inhibiting binding of [125I]Tyr(3)-NT to human Neurotensin receptor 3	ic50	0.7200	uM
4,5-dichloro-2-[(6-methyl-2-pyridinyl)carbamoyl]benzoic acid	1061998: Displacement of [3H]-neurotensin from sortilin (unknown origin) incubated 30 mins prior to [3H]-neurotensin addition measured after 6 hrs by scintillation proximity assay	ic50	0.8300	uM
2-[(6-methyl-2-pyridinyl)carbamoyl]-5-propan-2-ylbenzoic acid	1061998: Displacement of [3H]-neurotensin from sortilin (unknown origin) incubated 30 mins prior to [3H]-neurotensin addition measured after 6 hrs by scintillation proximity assay	ic50	1.1000	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-6-(methylamino)hexanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147067: Evaluated for binding affinity by inhibiting binding of [125I]Tyr(3)-NT to human Neurotensin receptor 3	ic50	1.1500	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2,7-diaminoheptanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147067: Evaluated for binding affinity by inhibiting binding of [125I]Tyr(3)-NT to human Neurotensin receptor 3	ic50	1.2000	uM
2-[(6-methoxy-2-pyridinyl)carbamoyl]-5-(trifluoromethyl)benzoic acid	1061998: Displacement of [3H]-neurotensin from sortilin (unknown origin) incubated 30 mins prior to [3H]-neurotensin addition measured after 6 hrs by scintillation proximity assay	ic50	1.3000	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2,5-diaminopentanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147067: Evaluated for binding affinity by inhibiting binding of [125I]Tyr(3)-NT to human Neurotensin receptor 3	ic50	1.4000	uM
5-chloro-2-[(6-methyl-2-pyridinyl)carbamoyl]benzoic acid	1061998: Displacement of [3H]-neurotensin from sortilin (unknown origin) incubated 30 mins prior to [3H]-neurotensin addition measured after 6 hrs by scintillation proximity assay	ic50	1.4000	uM
(2S)-2-[(3,5-dichlorobenzoyl)amino]-3-[(2-methylpropan-2-yl)oxy]propanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	1.5000	uM
5-bromo-2-[(6-chloro-2-pyridinyl)carbamoyl]benzoic acid	1061998: Displacement of [3H]-neurotensin from sortilin (unknown origin) incubated 30 mins prior to [3H]-neurotensin addition measured after 6 hrs by scintillation proximity assay	ic50	1.6000	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-6-(dimethylamino)hexanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147067: Evaluated for binding affinity by inhibiting binding of [125I]Tyr(3)-NT to human Neurotensin receptor 3	ic50	1.6200	uM
2-[(6-methyl-2-pyridinyl)carbamoyl]-5-nitrobenzoic acid	1061998: Displacement of [3H]-neurotensin from sortilin (unknown origin) incubated 30 mins prior to [3H]-neurotensin addition measured after 6 hrs by scintillation proximity assay	ic50	1.7000	uM
(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-amino-5-[[amino-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]methylidene]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoic acid	147067: Evaluated for binding affinity by inhibiting binding of [125I]Tyr(3)-NT to human Neurotensin receptor 3	ic50	1.7400	uM
5-bromo-2-[(2-methyl-4-pyridinyl)carbamoyl]benzoic acid	1061998: Displacement of [3H]-neurotensin from sortilin (unknown origin) incubated 30 mins prior to [3H]-neurotensin addition measured after 6 hrs by scintillation proximity assay	ic50	1.8000	uM
1-benzyl-3-tert-butylpyrazole-5-carboxylic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	2.0000	uM
[(4S)-4-amino-5-[[N’-[(4S)-4-amino-5-[(2S)-2-[[(2S)-1-[[(2S,3S)-1-[[(1S)-1-carboxy-3-methylbutyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-5-oxopentyl]carbamimidoyl]amino]-5-oxopentyl]-trimethylazanium	147067: Evaluated for binding affinity by inhibiting binding of [125I]Tyr(3)-NT to human Neurotensin receptor 3	ic50	2.0000	uM
3-tert-butyl-1-[(6-phenoxy-3-pyridinyl)methyl]pyrazole-5-carboxylic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	2.1000	uM
3-tert-butyl-1-[(3,5-dichlorophenyl)methyl]pyrazole-5-carboxylic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	2.1000	uM
(2S)-3-cyclohexyl-2-[(3,5-dichlorobenzoyl)amino]propanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	2.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases expression	3
Valproic Acid	affects expression, increases expression, increases methylation	3
trichostatin A	affects expression, decreases expression	2
Dexamethasone	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
selenomethylselenocysteine	increases expression	1
deoxynivalenol	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	decreases expression	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
yessotoxin	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
gardiquimod	decreases reaction, increases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Troglitazone	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cannabidiol	increases expression	1

ChEMBL screening assays

17 unique, capped per target: 15 binding, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2405877	Binding	Binding affinity to NTR3 (unknown origin)	The synthesis of neurotensin antagonist SR 48692 for prostate cancer research. — Bioorg Med Chem
CHEMBL4630496	ADMET	Substrate activity at human SORT1 expressed in HEK293 cells assessed as compound uptake at 100 nM incubated for 1 hr by confocal microscopy	Targeted Delivery of Antisense Oligonucleotides Using Neurotensin Peptides. — J Med Chem

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_B0XV	Abcam HeLa SORT1 KO	Cancer cell line	Female
CVCL_D9SP	Ubigene HEK293 SORT1 KO	Transformed cell line	Female
CVCL_TQ00	HAP1 SORT1 (-) 1	Cancer cell line	Male
CVCL_TQ01	HAP1 SORT1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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