NTS

Summary

NTS (neurotensin, HGNC:8038) is a protein-coding gene on chromosome 12q21.31, encoding Neurotensin/neuromedin N (P30990). Neurotensin may play an endocrine or paracrine role in the regulation of fat metabolism.

This gene encodes a common precursor for two peptides, neuromedin N and neurotensin. Neurotensin is a secreted tridecapeptide, which is widely distributed throughout the central nervous system, and may function as a neurotransmitter or a neuromodulator. It may be involved in dopamine-associated pathophysiological events, in the maintenance of gut structure and function, and in the regulation of fat metabolism. Neurotensin also exhibits antimicrobial activity against bacteria and fungi. Tissue-specific processing may lead to the formation in some tissues of larger forms of neuromedin N and neurotensin. The large forms may represent more stable peptides that are also biologically active.

Source: NCBI Gene 4922 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 27 total — 1 pathogenic
• MANE Select transcript: NM_006183

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8038
Approved symbol	NTS
Name	neurotensin
Location	12q21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000133636
Ensembl biotype	protein_coding
OMIM	162650
Entrez	4922

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000256010, ENST00000550879, ENST00000551529, ENST00000884137, ENST00000926967, ENST00000926968, ENST00000926969

RefSeq mRNA: 1 — MANE Select: NM_006183 NM_006183

CCDS: CCDS9029

Canonical transcript exons

ENST00000256010 — 4 exons

Exon	Start	End
ENSE00000909344	85876640	85876701
ENSE00000909345	85878345	85878569
ENSE00000993534	85882223	85882992
ENSE00002383191	85874295	85874476

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 97.60.

FANTOM5 (CAGE): breadth broad, TPM avg 18.9229 / max 6218.4113, expressed in 347 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127194	18.8484	344
127196	0.0356	10
127197	0.0190	8
206826	0.0146	5
127195	0.0053	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nasal cavity epithelium	UBERON:0005384	97.60	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.01	gold quality
nasal cavity mucosa	UBERON:0001826	93.76	gold quality
ileal mucosa	UBERON:0000331	91.75	gold quality
ileum	UBERON:0002116	91.66	silver quality
lateral nuclear group of thalamus	UBERON:0002736	91.64	gold quality
hypothalamus	UBERON:0001898	87.03	gold quality
epithelium of bronchus	UBERON:0002031	86.57	gold quality
bronchus	UBERON:0002185	86.46	gold quality
bronchial epithelial cell	CL:0002328	85.48	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.18	gold quality
lymph node	UBERON:0000029	83.44	gold quality
adenohypophysis	UBERON:0002196	81.12	gold quality
small intestine	UBERON:0002108	80.98	gold quality
mucosa of paranasal sinus	UBERON:0005030	80.87	gold quality
jejunal mucosa	UBERON:0000399	79.09	gold quality
pituitary gland	UBERON:0000007	78.30	gold quality
superficial temporal artery	UBERON:0001614	72.19	silver quality
dorsal plus ventral thalamus	UBERON:0001897	70.69	gold quality
Ammon’s horn	UBERON:0001954	69.48	gold quality
cortical plate	UBERON:0005343	69.27	gold quality
duodenum	UBERON:0002114	68.23	gold quality
vermiform appendix	UBERON:0001154	67.09	gold quality
adrenal tissue	UBERON:0018303	67.06	gold quality
lower esophagus mucosa	UBERON:0035834	66.84	gold quality
gall bladder	UBERON:0002110	64.87	gold quality
caecum	UBERON:0001153	63.88	gold quality
jejunum	UBERON:0002115	63.72	gold quality
rectum	UBERON:0001052	63.51	gold quality
superior vestibular nucleus	UBERON:0007227	62.56	silver quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-109979	yes	374.14
E-MTAB-6701	yes	11.16
E-MTAB-9388	yes	10.49
E-HCAD-1	yes	9.02
E-CURD-114	no	1195.33
E-MTAB-6524	no	492.10
E-ANND-3	no	2.25

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
PPP2CA	Repression
PTEN	Repression
SOCS1	Repression

Upstream regulators (CollecTRI, top): AP1, ATF1, CREB1, FOS, JUN, JUND, NR2F2, NR3C1, ZHX2

miRNA regulators (miRDB)

59 targeting NTS, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-543	99.52	69.03	2595

Literature-anchored findings (GeneRIF, showing 40)

• topography of its binding site to NT 1 receptor (PMID:11906607)
• Neurotensin induces protein kinase C-dependent protein kinase D activation and DNA synthesis in human pancreatic carcinoma cell line PANC-1. (PMID:11912133)
• The antimicrobial peptide neurotensin has activity against invasive microbes. (PMID:12074933)
• role in counteracting apoptosis in breast cancer cells (PMID:12150975)
• Neurotensin expressing neurons develop earlier than vasoactive intestinal polypeptide, vasopressin, and neuropeptide Y expressing neurons in the suprachiasmatic nucleus. (neurotensin) (PMID:12531461)
• neurotensin has a role in chronic mitogen-activated protein kinase activation and cancer progression (PMID:14699144)
• Analysis of the NTS genomic sequence revealed 2 intronic polymorphisms and 1 variant located in the 5’ untranslated region (UTR). None of the observed variants co-segregated with RLS and no disease-associated polymorphisms were detected (PMID:14743366)
• neurotensin secretion is mediated by protein kinase C-alpha/-delta and Rho/Rho kinase, and protein kinase D (PMID:15123666)
• Transcription of NT in the mitochrondria of BON cells in response to pharmacologic manipulation. (PMID:15358593)
• MARCKS-mediated neurotensin release occurs via protein kinase C-delta downstream of the Rho/ROK pathway (PMID:15623535)
• Ca2+ mobilization elicited by R-NT is via NTR1 (PMID:16087676)
• Proneurotensin 1-117 is a stable neurotensin precursor fragment identified in human circulation (PMID:16519961)
• NT uses PKC-dependent pathways to modulate GSK-3, which may play a role in the NT regulation of intestinal cell growth (PMID:16984735)
• Rap1 mediates cyclic AMP-stimulated neurotensin secretion downstream of both Epac and protein kinase A signaling pathways (PMID:17068197)
• NTS-induced growth signaling in a prostatic neoplasm cell line is sensitive to metabolic stress. (PMID:17289170)
• Neurotensin induces a striking increase in Hsp27 phosphorylation on Ser-82 in PANC-1 cells through convergent p38 MAPK, PKD, and PKD2 signaling. (PMID:17570131)
• The purpose of the current study is to further explore the NTS gene for potential functional variant(s) in its entire genomic and potential regulatory regions and their possible association with RLS symptoms. (PMID:17644423)
• study suggests two pathways of NTS1 overexpression during IBD-related oncogenesis: one triggered by NT overexpression, and a second associated with an activation of the APC/beta-catenin pathway (PMID:17870207)
• endogenous PKD1, PKD2, and Kidins220 co-exist with neurotensin-containing vesicles (PMID:18048355)
• NT autocrine and/or paracrine stimulation mediated by NTR3 may be a mechanism associated with the tumourigenesis of functioning adenomas. (PMID:18624930)
• Neurotensin signaling induces intracellular alkalinization and interleukin-8 expression in human pancreatic cancer cells. (PMID:19393580)
• The aim of this study was to provide an up-to-date review of the literature concerning the regulatory role of NT on the hypothalamic-anterior pituitary axons–REVIEW (PMID:19878995)
• The expression of NTS is identified as a prognostic marker in patients with malignant pleural mesothelioma. (PMID:19932148)
• neurotensin /NTR1 signaling in pancreatic cancer cells seems to promote the induction of a metastatic phenotype, in contrast to its varying effects on tumor cell proliferation. (PMID:20138826)
• Neurotensin is increased in serum of young children with autistic disorder. (PMID:20731814)
• Data show that neurotensin- and NTSR1-positive mmunohistochemistry staining in 60.4% and 59.7% of lung adenocarcinomas, respectively. (PMID:20810387)
• Expression of neurotensin and ghrelin systems are markedly altered in the temporal lobe of Alzheimer’s disease patients, which may contribute to the severe cognitive deficit observed in this pathology. (PMID:20858966)
• key regulatory elements in the promoter region that are involved in human NT/N (hNT/N) gene expression (PMID:21030593)
• IGF-1R activation represents a previously unrecognized key pathway involved in the mechanisms by which NT and NTR1 modulate colonic inflammation and inflammatory bowel disease. (PMID:21212273)
• NT acutely regulates D2 autoreceptor function and DA neuron excitability through PKC-mediated phosphorylation of the D2R, leading to heterologous receptor desensitization. (PMID:21233215)
• Results indicate that the counteraction of neurotensin and neurotensin receptor subtype-1 regulates the genesis and development of pancreatic carcinomas. (PMID:21272935)
• study found that inhibition of mTORC1 signaling by rapamycin, torin1, and shRNA-mediated knockdown enhances NT secretion by increasing NT gene expression in the endocrine cell line BON (PMID:21508335)
• Human, pig, and frog NT and [Gln(4)]NT and [D-Tyr(11)]NT adsorbed to the silver surface via the tyrosine ring, the oxygen atom of the deprotonated phenol group of Tyr(11), and the -CH(2)- unit(s), most probably of Tyr(11), Arg(9), and/or Leu(13). (PMID:21542591)
• determined the status of ERalpha and ERbeta in the myometrium and leiomyomas, atypical leiomyomas and leiomyosarcomas, concomitantly with the expression of NTS/NTS receptor 1 in these tumors (PMID:21623207)
• Neurotensin signaling activates microRNAs-21 and -155 and Akt, promotes tumor growth in mice, and is increased in human colon tumors. (PMID:21806946)
• CD133(+) liver tumor-initiating cells promote tumor angiogenesis, growth, and self-renewal through neurotensin/interleukin-8/CXCL1 signaling. (PMID:21994122)
• Endothelin-converting enzyme-1 (ECE-1) degrades NT in acidic conditions, and its activity is crucial for NTR1 recycling. (PMID:22416137)
• Neurotensin secretion is regulated by PI3 kinase p110 alpha and protein kinase B signaling pathways. (PMID:22700584)
• Proneurotensin expression in the tumor tissues indicated that this precursor was produced by small cell lung carcinoma tumors and secreted into plasma as the tumors grew. (PMID:22825476)
• Results showed that NT, NPY, and PGP 9.5 neurofibers are almost equally present in pseudocapsule of uterine fibroids as in normal myometrium of a no pregnant uterus. As all of these neuropeptides are present in the uterine muscle and can affect muscle contractility, uterine peristalsis and muscular healing. (PMID:22849656)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nts	ENSDARG00000057887
mus_musculus	Nts	ENSMUSG00000019890
rattus_norvegicus	Nts	ENSRNOG00000004179

Protein

Protein identifiers

Neurotensin/neuromedin N — P30990 (reviewed: P30990)

All UniProt accessions (3): P30990, G3V1X6, Q6FH20

UniProt curated annotations — full annotation on UniProt →

Function. Neurotensin may play an endocrine or paracrine role in the regulation of fat metabolism. It causes contraction of smooth muscle.

Subunit / interactions. Interacts with NTSR1. Interacts with SORT1. Interacts with SORL1.

Subcellular location. Secreted. Cytoplasmic vesicle. Secretory vesicle.

Post-translational modifications. Neurotensin is cleaved and degraded by Angiotensin-converting enzyme (ACE) and neprilysin (MME).

Similarity. Belongs to the neurotensin family.

RefSeq proteins (1): NP_006174* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008055	NeurotensiN	Family

Pfam: PF07421

UniProt features (10 total): peptide 3, site 2, strand 2, signal peptide 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
8VJY	X-RAY DIFFRACTION	1.95
3F6K	X-RAY DIFFRACTION	2
4PO7	X-RAY DIFFRACTION	2.66
5LUZ	X-RAY DIFFRACTION	2.7
6UP7	ELECTRON MICROSCOPY	4.2
2LNE	SOLUTION NMR
2LNF	SOLUTION NMR
2LNG	SOLUTION NMR
2LYW	SOLUTION NMR
2OYV	SOLUTION NMR
2OYW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30990-F1	61.51	0.00

Functional residue map

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

Catalytic / active sites (2): 160–161 (cleavage; by mme); 161–162 (cleavage; by ace and mme)

Post-translational modifications (1): 151

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 183 (showing top): MODULE_52, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_CIRCULATORY_SYSTEM_PROCESS, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, MODULE_64, CAGCTG_AP4_Q5, STOSSI_RESPONSE_TO_ESTRADIOL, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_SUSTAINDED_IN_ERYTHROCYTE_UP, MODULE_118, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, chr12q21, GOBP_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION

GO Biological Process (6): signal transduction (GO:0007165), neuropeptide signaling pathway (GO:0007218), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), blood vessel diameter maintenance (GO:0097746)

GO Molecular Function (4): neuropeptide hormone activity (GO:0005184), receptor ligand activity (GO:0048018), neuropeptide receptor binding (GO:0071855), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), transport vesicle (GO:0030133), axon terminus (GO:0043679), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by GPCR	2
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
gene expression	2
regulation of gene expression	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor signaling pathway	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
vascular process in circulatory system	1
blood circulation	1
regulation of tube diameter	1
hormone activity	1
neuropeptide activity	1
signaling receptor binding	1
signal transduction	1
signaling receptor activator activity	1
G protein-coupled receptor binding	1
binding	1
cellular anatomical structure	1
endomembrane system	1
cytoplasmic vesicle	1
neuron projection terminus	1
presynapse	1
distal axon	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1958 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NTS	NTSR1	P30989	999
NTS	NTSR2	O95665	994
NTS	SORT1	Q99523	991
NTS	TAC1	P20366	970
NTS	GRP	P07491	958
NTS	SST	P01166	941
NTS	KNG1	P01042	918
NTS	PDYN	P01213	906
NTS	CCK	P06307	886
NTS	MLN	P12872	879
NTS	OXT	P01178	868
NTS	TRH	P20396	867
NTS	NLN	Q9BYT8	855
NTS	SORL1	Q92673	852
NTS	VIP	P01282	850

IntAct

9 interactions, top by confidence:

A	B	Type	Score
SORT1	NGF	psi-mi:“MI:0407”(direct interaction)	0.680
SORT1	NTS	psi-mi:“MI:0915”(physical association)	0.610
NTSR1	NTS	psi-mi:“MI:0407”(direct interaction)	0.560
NTS	MFF	psi-mi:“MI:0915”(physical association)	0.560
	TOR1B	psi-mi:“MI:0914”(association)	0.350
MFF	NTS	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): MFF (Two-hybrid), NTS (Affinity Capture-MS), NTS (Affinity Capture-MS), NTS (Biochemical Activity), NTS (Reconstituted Complex), NTS (Reconstituted Complex), NTS (Affinity Capture-MS)

ESM2 similar proteins: O35417, O62647, O70176, P01210, P01211, P01212, P01213, P01214, P01282, P01283, P01360, P04094, P06300, P0DP56, P0DQF0, P13589, P16613, P17640, P18509, P19713, P20068, P22005, P30990, P32648, P33745, P41534, P41535, P45644, P47969, P48143, P48144, P48756, P50175, P56943, P69155, P69156, P69157, P81401, P81829, Q06145

Diamond homologs: P01156, P10673, P20068, P30990, Q9D3P9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NTS	up-regulates	NTSR1	binding
NTS	down-regulates	NTSR2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
625562	GRCh37/hg19 12q21.31-21.32(chr12:82183041-88755577)	Pathogenic

SpliceAI

361 predictions. Top by Δscore:

Variant	Effect	Δscore
12:85874474:CAGGT:C	donor_loss	1.0000
12:85874477:G:GG	donor_gain	1.0000
12:85876634:A:AG	acceptor_gain	1.0000
12:85876635:CTCA:C	acceptor_loss	1.0000
12:85876636:TCAG:T	acceptor_loss	1.0000
12:85876637:CAG:C	acceptor_loss	1.0000
12:85876638:A:AG	acceptor_gain	1.0000
12:85876638:AGAT:A	acceptor_loss	1.0000
12:85876639:G:GA	acceptor_loss	1.0000
12:85876639:G:GG	acceptor_gain	1.0000
12:85876697:CAAAG:C	donor_loss	1.0000
12:85876698:AAAGG:A	donor_loss	1.0000
12:85876699:AAGGT:A	donor_loss	1.0000
12:85876700:AG:A	donor_loss	1.0000
12:85876701:GG:G	donor_loss	1.0000
12:85876702:GTAA:G	donor_loss	1.0000
12:85876703:T:G	donor_loss	1.0000
12:85882221:A:AG	acceptor_gain	1.0000
12:85882222:G:GA	acceptor_gain	1.0000
12:85882222:GTTA:G	acceptor_gain	1.0000
12:85876635:C:G	acceptor_gain	0.9900
12:85878504:G:GT	donor_gain	0.9900
12:85878567:G:GT	donor_gain	0.9900
12:85878567:G:T	donor_gain	0.9900
12:85882220:CAG:C	acceptor_loss	0.9900
12:85882221:AGT:A	acceptor_loss	0.9900
12:85882222:G:GT	acceptor_loss	0.9900
12:85882222:GT:G	acceptor_gain	0.9900
12:85882222:GTT:G	acceptor_gain	0.9900
12:85882222:GTTAA:G	acceptor_gain	0.9900

AlphaMissense

1132 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:85882347:T:C	I162T	0.995
12:85882302:T:C	I147T	0.993
12:85882308:A:T	K149I	0.993
12:85882309:A:C	K149N	0.992
12:85882309:A:T	K149N	0.992
12:85882353:A:T	K164I	0.992
12:85882354:A:C	K164N	0.992
12:85882354:A:T	K164N	0.992
12:85882339:A:C	R159S	0.990
12:85882339:A:T	R159S	0.990
12:85882336:A:C	R158S	0.989
12:85882336:A:T	R158S	0.989
12:85882350:T:C	L163P	0.989
12:85882357:A:C	R165S	0.989
12:85882357:A:T	R165S	0.989
12:85878393:T:C	C62R	0.986
12:85882335:G:C	R158T	0.986
12:85878542:T:G	C111W	0.985
12:85882311:G:C	R150P	0.985
12:85882347:T:A	I162K	0.985
12:85878541:G:A	C111Y	0.984
12:85882308:A:C	K149T	0.984
12:85882338:G:C	R159T	0.984
12:85878540:T:C	C111R	0.983
12:85882353:A:C	K164T	0.983
12:85878540:T:A	C111S	0.982
12:85878541:G:C	C111S	0.982
12:85882302:T:G	I147S	0.982
12:85882305:T:C	L148P	0.982
12:85882350:T:A	L163H	0.982

dbSNP variants (sampled 300 via entrez): RS1000086228 (12:85880929 G>A,C), RS1000168927 (12:85880799 A>G), RS1000418544 (12:85881276 G>A), RS1000706589 (12:85873878 C>A), RS1000835266 (12:85872933 A>C), RS1000902431 (12:85872474 A>T), RS1001060020 (12:85879954 T>C), RS1001234697 (12:85878037 C>A), RS1001257522 (12:85880603 G>A), RS1001344162 (12:85881285 T>C), RS1001629818 (12:85880821 C>G,T), RS1001785669 (12:85873581 A>C), RS1001807228 (12:85874291 T>C), RS1001816970 (12:85873352 A>G), RS1002177561 (12:85879052 T>C)

Disease associations

OMIM: gene MIM:162650 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009391_22	Metabolite levels	6.000000e-06
GCST009391_23	Metabolite levels	6.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

Binding affinities (BindingDB)

3 measured of 4 human assays (5 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S)-2-(2,3-dihydro-1,4-benzodioxin-6-ylmethylamino)-5,5-dimethylhexanoic acid	IC50	330 nM	US-20250268854: 2-AMINO-5,5-DIMETHYLHEXANOIC ACID DERIVATIVES AS SORTILIN MODULATORS FOR USE IN THE TREATMENT OF DISEASE OF THE CENTRAL NERVOUS SYSTEM
(2S)-2-(3,4-dihydro-2H-chromen-6-ylmethylamino)-5,5-dimethylhexanoic acid	IC50	470 nM	US-20250268854: 2-AMINO-5,5-DIMETHYLHEXANOIC ACID DERIVATIVES AS SORTILIN MODULATORS FOR USE IN THE TREATMENT OF DISEASE OF THE CENTRAL NERVOUS SYSTEM
SR 147778	KI	1000 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	7
methylmercuric chloride	affects expression, increases expression	2
sodium arsenite	decreases expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
rottlerin	affects reaction, increases chemical synthesis, decreases reaction, increases activity, increases phosphorylation	2
RTKI cpd	increases expression, increases activity, increases phosphorylation, increases secretion, decreases reaction	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression, decreases reaction	2
Staurosporine	increases chemical synthesis, increases reaction, decreases reaction, increases activity, increases phosphorylation (+1 more)	2
Okadaic Acid	decreases activity, increases reaction, increases expression	2
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects methylation	1
phosphoramidon	increases phosphorylation, decreases reaction, increases activity	1
trichostatin A	increases expression	1
osteum	decreases reaction, increases secretion	1
chelerythrine	increases activity	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
bicalutamide	decreases response to substance	1
1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione	decreases reaction, increases activity, increases phosphorylation	1
Ro 31-8220	increases chemical synthesis, increases activity, decreases reaction, affects reaction	1
bisindolylmaleimide I	decreases reaction, increases activity, increases reaction, affects reaction, increases chemical synthesis (+1 more)	1
batimastat	decreases reaction, increases activity, increases phosphorylation	1
Go 6976	increases activity, decreases activity, decreases reaction, increases chemical synthesis, increases reaction	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases activity, increases phosphorylation	1
bisindolylmaleimide	increases phosphorylation, decreases reaction, increases activity	1
4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline	decreases reaction, increases activity, increases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
dexloxiglumide	decreases reaction, increases secretion	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery