NTRK2

Summary

NTRK2 (neurotrophic receptor tyrosine kinase 2, HGNC:8032) is a protein-coding gene on chromosome 9q21.33, encoding BDNF/NT-3 growth factors receptor (Q16620). Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity. In precision oncology, NTRK1 Amplification OR NTRK3 Amplification OR NTRK2 Amplification confers sensitivity to Entrectinib in Cancer (CIViC Level B).

This gene encodes a member of the neurotrophic tyrosine receptor kinase (NTRK) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation. Mutations in this gene have been associated with obesity and mood disorders. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 4915 — RefSeq curated summary.

At a glance

• Gene–disease (curated): obesity, hyperphagia, and developmental delay (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 13
• Clinical variants (ClinVar): 844 total — 6 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 71
• Druggable target: yes — 50 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• MANE Select transcript: NM_006180

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8032
Approved symbol	NTRK2
Name	neurotrophic receptor tyrosine kinase 2
Location	9q21.33
Locus type	gene with protein product
Status	Approved
Aliases	TRKB
Ensembl gene	ENSG00000148053
Ensembl biotype	protein_coding
OMIM	600456
Entrez	4915

Gene structure

Transcript identifiers

Ensembl transcripts: 60 — 38 protein_coding, 12 protein_coding_CDS_not_defined, 9 retained_intron, 1 nonsense_mediated_decay

ENST00000277120, ENST00000304053, ENST00000323115, ENST00000359847, ENST00000376208, ENST00000376213, ENST00000395882, ENST00000685095, ENST00000685209, ENST00000685387, ENST00000685425, ENST00000685463, ENST00000685720, ENST00000686259, ENST00000686322, ENST00000686324, ENST00000686332, ENST00000686443, ENST00000686496, ENST00000686542, ENST00000686874, ENST00000687136, ENST00000687148, ENST00000687386, ENST00000687596, ENST00000687636, ENST00000687690, ENST00000688013, ENST00000688041, ENST00000688241, ENST00000688333, ENST00000688850, ENST00000688854, ENST00000688978, ENST00000689301, ENST00000689651, ENST00000689685, ENST00000689815, ENST00000690044, ENST00000690163, ENST00000690281, ENST00000690882, ENST00000691415, ENST00000691567, ENST00000691710, ENST00000691788, ENST00000692181, ENST00000692389, ENST00000692473, ENST00000692506, ENST00000692654, ENST00000692762, ENST00000692804, ENST00000693109, ENST00000693127, ENST00000693313, ENST00000693384, ENST00000693539, ENST00000884757, ENST00000884758

RefSeq mRNA: 27 — MANE Select: NM_006180 NM_001007097, NM_001018064, NM_001018065, NM_001018066, NM_001291937, NM_001369532, NM_001369533, NM_001369534, NM_001369535, NM_001369536, NM_001369537, NM_001369538, NM_001369539, NM_001369540, NM_001369541, NM_001369542, NM_001369543, NM_001369544, NM_001369545, NM_001369546, NM_001369547, NM_001369548, NM_001369549, NM_001369550, NM_001369551, NM_001369552, NM_006180

CCDS: CCDS35050, CCDS35051, CCDS35052, CCDS35053, CCDS6671, CCDS94427, CCDS94428, CCDS94429, CCDS94430, CCDS94431

Canonical transcript exons

ENST00000277120 — 19 exons

Exon	Start	End
ENSE00000982956	84723573	84723709
ENSE00000982960	84751986	84752085
ENSE00001025534	84741892	84741927
ENSE00001090518	84934162	84934292
ENSE00001090519	84867243	84867431
ENSE00001090521	84955283	84955517
ENSE00001090522	84948462	84948634
ENSE00001197359	84861040	84861087
ENSE00001264498	84744973	84745073
ENSE00001264511	84727654	84727959
ENSE00001264518	84724224	84724356
ENSE00001264584	85021252	85027054
ENSE00001343633	84670377	84670960
ENSE00001523199	84669729	84669888
ENSE00001714994	85020206	85020364
ENSE00003550768	84702159	84702233
ENSE00003565670	84702348	84702419
ENSE00003615967	84707844	84707912
ENSE00003674598	84710637	84710791

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 99.59.

FANTOM5 (CAGE): breadth broad, TPM avg 33.4603 / max 2333.7886, expressed in 543 samples.

FANTOM5 promoters (50 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97119	10.0909	377
97117	6.2939	308
97107	3.7839	171
97120	2.5894	270
97104	1.4936	157
97155	0.8607	127
97113	0.6503	155
97127	0.6045	152
97114	0.4966	118
97118	0.4754	138

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cranial nerve II	UBERON:0000941	99.59	gold quality
lateral globus pallidus	UBERON:0002476	99.57	gold quality
CA1 field of hippocampus	UBERON:0003881	99.47	gold quality
globus pallidus	UBERON:0001875	99.40	gold quality
medial globus pallidus	UBERON:0002477	99.39	gold quality
choroid plexus epithelium	UBERON:0003911	99.28	gold quality
superior vestibular nucleus	UBERON:0007227	99.27	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.11	gold quality
ventral tegmental area	UBERON:0002691	99.09	gold quality
medulla oblongata	UBERON:0001896	98.95	gold quality
postcentral gyrus	UBERON:0002581	98.88	gold quality
parietal lobe	UBERON:0001872	98.86	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.75	gold quality
amygdala	UBERON:0001876	98.65	gold quality
subthalamic nucleus	UBERON:0001906	98.61	gold quality
caudate nucleus	UBERON:0001873	98.55	gold quality
substantia nigra pars compacta	UBERON:0001965	98.52	gold quality
inferior olivary complex	UBERON:0002127	98.45	gold quality
temporal lobe	UBERON:0001871	98.42	gold quality
putamen	UBERON:0001874	98.42	gold quality
nucleus accumbens	UBERON:0001882	98.41	gold quality
entorhinal cortex	UBERON:0002728	98.41	gold quality
olfactory bulb	UBERON:0002264	98.33	gold quality
calcaneal tendon	UBERON:0003701	98.22	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.20	gold quality
inferior vagus X ganglion	UBERON:0005363	97.94	gold quality
corpus callosum	UBERON:0002336	97.93	gold quality
Ammon’s horn	UBERON:0001954	97.84	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.83	gold quality
hypothalamus	UBERON:0001898	97.80	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	2278.23
E-GEOD-84465	yes	2191.34
E-MTAB-10485	yes	634.24
E-HCAD-35	yes	76.15
E-MTAB-10287	yes	47.83
E-CURD-119	yes	47.66
E-HCAD-10	yes	45.55
E-MTAB-7316	yes	23.32
E-HCAD-4	yes	16.74
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ANKRD11, ASH1L, CREB1, DLX1, DLX2, DLX4, FMR1, GLI1, HIF1A, KLF7, MYCN, POU4F1, RORA, RUNX3, TCF3, THRA, WT1

miRNA regulators (miRDB)

178 targeting NTRK2, 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-6873-3P	100.00	71.42	2626
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-4778-3P	99.93	70.40	1818

Literature-anchored findings (GeneRIF, showing 40)

• analysis of TrkB gene reveals novel gene length and splicing mechanism (PMID:11798182)
• Alterations in trkB mRNA in the human prefrontal cortex throughout the lifespan. (PMID:11849294)
• discrete domain of the TrkB receptor defines the binding sites for BDNF and NT-4 (PMID:11855816)
• This review discusses the importance of TrkB/brain-derived neurotrophic factor signaling pathway interactions in memory processes. (PMID:12719654)
• expressed in human neuroblastoma cells in response to retinoic acid (PMID:12808116)
• Messenger RNA levels of BDNF and trk B were significantly reduced, independently and as a ratio to neuron-specific enolase, in both prefrontal cortex and hippocampus in suicide subjects, as compared with those in control subjects. (PMID:12912764)
• Observed immunohistochemical differences in TrkB between schizophrenic and normal cases may indicate the existence of TrkB dysfunction in schizophrenic brain, and this dysfunction may be one of the factors involved in the pathogenesis of schizophrenia. (PMID:12921913)
• Results suggest that basic helix-loop-helix proteins provide a direct transcriptional link between a cell cycle inhibitor, p21(Cip1), and a neurotrophic receptor, Trk. (PMID:15024057)
• An 8-year-old male with a complex developmental syndrome and severe obesity was heterozygous for a de novo missense mutation resulting in a Y722C substitution in the neurotrophin receptor TrkB. (PMID:15494731)
• upregulation of genes involved in neoplasm invasiveness or therapy resistance (PMID:15637590)
• We investigated the involvement of signaling mediated by brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase TrkB in producing the altered GABA-related gene expression in schizophrenia. (PMID:15647480)
• MM cells express TrkB, and respond to BDNF by activating MAPK and PI3K/Akt signaling cascades (PMID:15657181)
• Contribution of NTRK2 to the genetic susceptibility of eating disorders, mainly anorexia nervosa, harm avoidance and body mass index. (PMID:15838534)
• The neurotrophin receptor TrkB cooperates with c-Met in enhancing neuroblastoma invasiveness (PMID:16051641)
• Results showed that TrkB receptor was identified in oocytes and GCs and the transcripts of all forms of TrkB receptor were identified in the samples. (PMID:16648150)
• TRKb is likely to play roles not only in early growth but also in maintenance of neurons throughout life. (PMID:16713371)
• These results strongly suggest that NTRK2 is a susceptibility gene for ND. These findings imply that NTRK2 plays a role in the etiology of ND and represents an important biological candidate for further investigation. (PMID:16713586)
• Light and electron microscopy immunohistochemistry showed that tonsillar samples were positive for TrkB. (PMID:16786155)
• Human lung adenocarcinomas express TrkA and TrkB, but not TrkC; A549 cells, express mRNA transcripts encoding nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), TrkA, TrkB, and p75, and high protein levels of TrkA and TrkB. (PMID:16862449)
• EGFR and TrkB crosstalk each other in response to EGF and BDNF, leading to cell survival pathway activation in ovarian cancer cells. (PMID:16964397)
• TrkB may be a mediator as well as a marker of carcinogenesis and metastasis. (PMID:17008023)
• Support role for NTRK2 gene in addiction in Caucasian population with antisocial alcohol dependence. (PMID:17200667)
• Decreased TrkB transgene expression or retina-specific deletion of TrkB, the cognate receptor for BDNF, retards the laminar refinement of ganglion cell dendrites. (PMID:17611278)
• TrkB kinase activity is required and, unexpectedly, also sufficient for anoikis suppression, tumor formation, and experimental metastasis (PMID:17616679)
• TrkB abnormal expression rate of nasopharyngeal carcinoma with lymph node metastasis was higher than that of NPC without lymph node metastasis. (PMID:17674765)
• Thus, these results do not support a significant role for TrkB sequence variation in the etiology of schizophrenia. (PMID:17720314)
• TrkB expression may be greater in women with endometriosis compared to women without endometriosis. (PMID:17873329)
• We used a linkage disequilibrium (LD)-mapping approach to investigate the role that BDNF and its specific receptor neurotrophic tyrosine kinase receptor type 2 (NTRK2) may play in increasing susceptibility to OCD. (PMID:17884018)
• the BDNF/TrkB signaling pathway could be involved, at least in part, in multiple myeloma-induced angiogenesis (PMID:17889702)
• results suggest that NTRK2 may be a genetic susceptibility gene contributing to Alzheimer disease pathology (PMID:17918233)
• in astrocytomas, Trk receptors (TrkA, TrkB, TrkC) expression, but not p75NTR may promote tumor growth independently of grade (PMID:17971243)
• NTRK2 gene that encodes the BDNF receptor, TRKB, was overexpressed in MeCP2 deficient human and mouse brains either directly or as an attempt to compensate for BDNF deficiency (PMID:18075316)
• TrkB might mediate anoikis suppression by activating the PI3K-AKT pathway in ovarian cancer cells. (PMID:18201274)
• Review provides future perspective on BDNF/TrkB signaling as a novel molecular target to correct the pathogenesis of schizophrenia and improve its long-term clinical outcome by treatments with conventional and adjunctive drugs. (PMID:18253057)
• somatic mutations in the tyrosine kinase domain of NTRK2 gene are frequent in large cell neuroendocrine carcinomas. Such mutational events could represent an important step in the cancerogenesis of these tumors (PMID:18293376)
• A potential role of all neurotrophins, through their different receptors, in pituitary functions. (PMID:18319596)
• Retinal brain-derived neurotrophic factor BDNF/TrkB signaling has a primary role in the development of inner retinal neuronal circuits in conditional knockout mice. This action is not a secondary effect due to loss of visual signaling in the outer retina. (PMID:18511296)
• This study found it affects nicotine dependence through interactions with CHRNA4 and NTRK2. (PMID:18534558)
• These data demonstrate that TrkB may contribute to metastasis by facilitating formation of multicellular aggregations and induce their resistance to detachment-induced apoptosis. (PMID:18595003)
• The presence of brain-derived neurotrophic factor (BDNF) and its receptor in the human intervertebral disc is shown at the translational level in cultured human annulus cells. (PMID:18637190)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ntrk2a	ENSDARG00000059897
danio_rerio	ntrk2b	ENSDARG00000098511
mus_musculus	Ntrk2	ENSMUSG00000055254
rattus_norvegicus	Ntrk2	ENSRNOG00000018839

Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR2 (ENSG00000066468), FGFR3 (ENSG00000068078), EPHA8 (ENSG00000070886), FGFR1 (ENSG00000077782), EPHA6 (ENSG00000080224), TYRO3 (ENSG00000092445), FLT1 (ENSG00000102755), MET (ENSG00000105976), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), FLT3 (ENSG00000122025), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), IGF1R (ENSG00000140443), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715)

Protein

Protein identifiers

BDNF/NT-3 growth factors receptor — Q16620 (reviewed: Q16620)

Alternative names: GP145-TrkB, Neurotrophic tyrosine kinase receptor type 2, TrkB tyrosine kinase, Tropomyosin-related kinase B

All UniProt accessions (13): Q16620, A0A8I5KPC6, A0A8I5KR47, A0A8I5KUH9, A0A8I5KUV8, A0A8I5KUZ1, A0A8I5KVH8, A0A8I5KYI3, A0A8I5KZB7, A0A8I5QKP8, A0A8J8YUT9, Q548C2, Q5VWE5

UniProt curated annotations — full annotation on UniProt →

Function. Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity. Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2. Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia.

Subunit / interactions. Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Interacts (phosphorylated upon activation by BDNF) with SHC1; mediates SHC1 phosphorylation and activation. Interacts (phosphorylated upon activation by BDNF) with PLCG1 and/or PLCG2; mediates PLCG1 phosphorylation and activation. Interacts with SH2B1 and SH2B2. Interacts with NGFR; may regulate the ligand specificity of the receptor. Interacts with SORCS2; this interaction is important for normal targeting to post-synaptic densities in response to high-frequency stimulation. Interacts (phosphorylated upon ligand-binding) with SH2D1A; regulates NTRK2. Interacts with SQSTM1 and KIDINS220. Interacts (phosphorylated upon ligand-binding) with FRS2; activates the MAPK signaling pathway. Interacts with APPL1. Interacts with MAPK8IP3/JIP3 and KLC1; interaction with KLC1 is mediated by MAPK8IP3/JIP3. Interacts with SORL1; this interaction facilitates NTRK2 trafficking between synaptic plasma membranes, postsynaptic densities and cell soma, hence positively regulates BDNF signaling. Interacts with SLITRK2.

Subcellular location. Cell membrane. Endosome membrane. Early endosome membrane. Cell projection. Axon. Dendrite. Cytoplasm. Perinuclear region. Postsynaptic density.

Tissue specificity. Isoform TrkB is expressed in the central and peripheral nervous system. In the central nervous system (CNS), expression is observed in the cerebral cortex, hippocampus, thalamus, choroid plexus, granular layer of the cerebellum, brain stem, and spinal cord. In the peripheral nervous system, it is expressed in many cranial ganglia, the ophthalmic nerve, the vestibular system, multiple facial structures, the submaxillary glands, and dorsal root ganglia. Isoform TrkB-T1 is mainly expressed in the brain but also detected in other tissues including pancreas, kidney and heart. Isoform TrkB-T-Shc is predominantly expressed in the brain.

Post-translational modifications. Phosphorylated. Undergoes ligand-mediated autophosphorylation that is required for interaction with SHC1 and PLCG1 and other downstream effectors. Isoform TrkB-T-Shc is not phosphorylated. Ubiquitinated. Undergoes polyubiquitination upon activation; regulated by NGFR. Ubiquitination regulates the internalization of the receptor.

Disease relevance. Developmental and epileptic encephalopathy 58 (DEE58) [MIM:617830] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE58 is an autosomal dominant condition characterized by onset of refractory seizures in the first days or months of life. The disease may be caused by variants affecting the gene represented in this entry. Obesity, hyperphagia, and developmental delay (OBHD) [MIM:613886] A disorder characterized by early-onset obesity, hyperphagia, and severe developmental delay in motor function, speech, and language. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The neuronal activity and the influx of calcium positively regulate the kinase activity and the internalization of the receptor which are both important for active signaling. Regulated by NGFR that may control the internalization of the receptor. NGFR may also stimulate the activation by BDNF compared to NTF3 and NTF4. SH2D1A inhibits the autophosphorylation of the receptor, and alters the recruitment and activation of downstream effectors and signaling cascades. The formation of active receptors dimers able to fully transduce the ligand-mediated signal, may be negatively regulated by the formation of inactive heterodimers with the non-catalytic isoforms.

Miscellaneous. Trk also stands for tropomyosin-related kinase since the first Trk was isolated as an oncogenic protein which was the result of a fusion between the tropomyosin gene TPM3 and NTRK1. Non-catalytic isoform.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

Isoforms (7)

UniProt ID	Names	Canonical?
Q16620-1	TrkB, gp145-TrkB	yes
Q16620-2	TrkB-T1
Q16620-3	TrkB-T-Shc
Q16620-4	4
Q16620-5	5
Q16620-6	TrkB-T-TK
Q16620-7	TrkB-N-T1

RefSeq proteins (27): NP_001007098, NP_001018074, NP_001018075, NP_001018076, NP_001278866, NP_001356461, NP_001356462, NP_001356463, NP_001356464, NP_001356465, NP_001356466, NP_001356467, NP_001356468, NP_001356469, NP_001356470, NP_001356471, NP_001356472, NP_001356473, NP_001356474, NP_001356475, NP_001356476, NP_001356477, NP_001356478, NP_001356479, NP_001356480, NP_001356481, NP_006171* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000372	LRRNT	Domain
IPR000483	Cys-rich_flank_reg_C	Domain
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR002011	Tyr_kinase_rcpt_2_CS	Conserved_site
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020455	NTRK2	Family
IPR020635	Tyr_kinase_cat_dom	Domain
IPR020777	NTRK	Family
IPR031635	NTRK_LRRCT	Domain
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050122	RTK	Family

Pfam: PF01462, PF07679, PF07714, PF13855, PF16920

Enzyme classification (BRENDA):

• EC 2.7.10.1 — receptor protein-tyrosine kinase (BRENDA: 44 organisms, 214 substrates, 574 inhibitors, 11 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0011–0.129	4
AC-DYFE-6-CHLORO-W-NHME	0.0051	1
AC-DYFGW-NHME	0.07	1
YFEW	0.232	1

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (106 total): strand 22, helix 18, glycosylation site 11, sequence variant 11, splice variant 8, disulfide bond 6, domain 5, modified residue 5, turn 4, site 3, region of interest 2, binding site 2, topological domain 2, repeat 2, signal peptide 1, chain 1, compositionally biased region 1, active site 1, transmembrane region 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
4ASZ	X-RAY DIFFRACTION	1.7
4AT5	X-RAY DIFFRACTION	1.71
4AT3	X-RAY DIFFRACTION	1.77
1WWB	X-RAY DIFFRACTION	2.1
4AT4	X-RAY DIFFRACTION	2.36
5MO9	X-RAY DIFFRACTION	2.59
1HCF	X-RAY DIFFRACTION	2.7
2MFQ	SOLUTION NMR
8OYD	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16620-F1	77.53	0.45

Antibody-complex structures (SAbDab): 1 — 5MO9

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 (4): 676 (proton acceptor); 516 (interaction with shc1); 706 (interaction with sh2d1a); 817 (interaction with plcg1)

Ligand- & substrate-binding residues (2): 544–552; 572

Post-translational modifications (5): 516, 702, 706, 707, 817

Disulfide bonds (6): 32–38, 36–45, 152–176, 154–194, 218–266, 302–345

Glycosylation sites (11): 67, 95, 121, 178, 205, 241, 254, 280, 325, 338, 412

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-187024	NGF-independant TRKA activation
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-9024909	BDNF activates NTRK2 (TRKB) signaling
R-HSA-9025046	NTF3 activates NTRK2 (TRKB) signaling
R-HSA-9026357	NTF4 activates NTRK2 (TRKB) signaling
R-HSA-9026519	Activated NTRK2 signals through RAS
R-HSA-9026527	Activated NTRK2 signals through PLCG1
R-HSA-9028335	Activated NTRK2 signals through PI3K
R-HSA-9028731	Activated NTRK2 signals through FRS2 and FRS3
R-HSA-9032500	Activated NTRK2 signals through FYN
R-HSA-9032759	NTRK2 activates RAC1
R-HSA-9032845	Activated NTRK2 signals through CDK5

MSigDB gene sets: 616 (showing top): PID_SHP2_PATHWAY, GOBP_CIRCADIAN_RHYTHM, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_GLUTAMATE_SECRETION, TAATAAT_MIR126, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_SYNAPSE_ASSEMBLY, JAEGER_METASTASIS_DN, NKX25_02, ZHAN_MULTIPLE_MYELOMA_MF_UP, KEGG_MAPK_SIGNALING_PATHWAY

GO Biological Process (41): vasculogenesis (GO:0001570), neuron migration (GO:0001764), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), learning (GO:0007612), circadian rhythm (GO:0007623), feeding behavior (GO:0007631), positive regulation of cell population proliferation (GO:0008284), positive regulation of gene expression (GO:0010628), positive regulation of neuron projection development (GO:0010976), glutamate secretion (GO:0014047), neuronal action potential propagation (GO:0019227), central nervous system neuron development (GO:0021954), cerebral cortex development (GO:0021987), myelination in peripheral nervous system (GO:0022011), neuron differentiation (GO:0030182), brain-derived neurotrophic factor receptor signaling pathway (GO:0031547), mechanoreceptor differentiation (GO:0042490), regulation of GTPase activity (GO:0043087), positive regulation of MAPK cascade (GO:0043410), negative regulation of neuron apoptotic process (GO:0043524), retinal rod cell development (GO:0046548), protein autophosphorylation (GO:0046777), oligodendrocyte differentiation (GO:0048709), peripheral nervous system neuron development (GO:0048935), positive regulation of axonogenesis (GO:0050772), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of synapse assembly (GO:0051965), long-term synaptic potentiation (GO:0060291), cellular response to amino acid stimulus (GO:0071230), trans-synaptic signaling by BDNF, modulating synaptic transmission (GO:0099183), negative regulation of amyloid-beta formation (GO:1902430), cellular response to brain-derived neurotrophic factor stimulus (GO:1990416), negative regulation of anoikis (GO:2000811), protein phosphorylation (GO:0006468), cell communication (GO:0007154), nervous system development (GO:0007399), cell differentiation (GO:0030154), neurotrophin signaling pathway (GO:0038179), regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051896), retina development in camera-type eye (GO:0060041)

GO Molecular Function (15): protease binding (GO:0002020), ATP binding (GO:0005524), protein homodimerization activity (GO:0042803), neurotrophin binding (GO:0043121), brain-derived neurotrophic factor binding (GO:0048403), brain-derived neurotrophic factor receptor activity (GO:0060175), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein tyrosine kinase activity (GO:0004713), transmembrane receptor protein tyrosine kinase activity (GO:0004714), neurotrophin receptor activity (GO:0005030), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (18): early endosome (GO:0005769), cytosol (GO:0005829), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), axon (GO:0030424), dendrite (GO:0030425), early endosome membrane (GO:0031901), terminal bouton (GO:0043195), dendritic spine (GO:0043197), signaling receptor complex (GO:0043235), axon terminus (GO:0043679), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), endosome (GO:0005768), endosome membrane (GO:0010008), membrane (GO:0016020), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by NTRK2 (TRKB)	9
Intracellular signaling by second messengers	1
Activation of TRKA receptors	1
PI3K/AKT Signaling in Cancer	1
Negative regulation of the PI3K/AKT network	1
Activated NTRK2 signals through FYN	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cell differentiation	2
generation of neurons	2
neurotrophin binding	2
endosome	2
cytoplasm	2
neuron projection	2
presynapse	2
blood vessel morphogenesis	1
cell migration	1
enzyme-linked receptor protein signaling pathway	1
learning or memory	1
rhythmic process	1
behavior	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
dicarboxylic acid transport	1
acidic amino acid transport	1
secretion by cell	1
nitrogen compound transport	1
transmission of nerve impulse	1
nervous system process	1
action potential propagation	1
central nervous system neuron differentiation	1
neuron development	1
pallium development	1
anatomical structure development	1
Schwann cell development	1
peripheral nervous system axon ensheathment	1
myelination	1
cell surface receptor protein tyrosine kinase signaling pathway	1
neuron differentiation	1
GTPase activity	1

Protein interactions and networks

STRING

4958 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NTRK2	NGF	P01138	999
NTRK2	NTF3	P20783	999
NTRK2	BDNF	P23560	999
NTRK2	NTF4	P34130	999
NTRK2	GDNF	P39905	994
NTRK2	SHC1	P29353	993
NTRK2	NGFR	P08138	985
NTRK2	NTRK1	P04629	978
NTRK2	NTRK3	Q16288	951
NTRK2	EFNA5	P52803	928
NTRK2	SORT1	Q99523	882
NTRK2	NR3C1	P04150	868
NTRK2	PTPN11	Q06124	858
NTRK2	SHC3	Q92529	822
NTRK2	ADORA2A	P29274	809

IntAct

54 interactions, top by confidence:

A	B	Type	Score
EGFR	NTRK2	psi-mi:“MI:0915”(physical association)	0.650
NTRK2	EGFR	psi-mi:“MI:2364”(proximity)	0.650
NTRK2	EGFR	psi-mi:“MI:0915”(physical association)	0.650
Cdk5	NTRK2	psi-mi:“MI:0407”(direct interaction)	0.560
NTRK2	Cdk5	psi-mi:“MI:0407”(direct interaction)	0.560
NTRK2	SMAD4	psi-mi:“MI:0915”(physical association)	0.550
SMAD4	NTRK2	psi-mi:“MI:2364”(proximity)	0.550
NTRK2	NTRK3	psi-mi:“MI:0915”(physical association)	0.540
NTRK2	NTRK2	psi-mi:“MI:0915”(physical association)	0.490
NTRK2	PKM	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
SORT1	NTRK2	psi-mi:“MI:0407”(direct interaction)	0.440
NTF4	NTRK2	psi-mi:“MI:2364”(proximity)	0.410
NR3C1	NTRK2	psi-mi:“MI:0915”(physical association)	0.400
DLG4	NTRK2	psi-mi:“MI:0915”(physical association)	0.400
	NTRK2	psi-mi:“MI:0915”(physical association)	0.400
HSP90AB1	NTRK2	psi-mi:“MI:0915”(physical association)	0.400
AP1B1	NTRK2	psi-mi:“MI:0915”(physical association)	0.370
NTRK2	POLR2G	psi-mi:“MI:0915”(physical association)	0.370
NMNAT1	NTRK2	psi-mi:“MI:0915”(physical association)	0.370
VPS35	ILVBL	psi-mi:“MI:0914”(association)	0.350
NTRK2	GNAI3	psi-mi:“MI:0914”(association)	0.350
NTRK3	ILVBL	psi-mi:“MI:0914”(association)	0.350
SCN2A	IGLL5	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SYT5	psi-mi:“MI:0914”(association)	0.350

BioGRID (178): NTRK2 (Two-hybrid), NTRK2 (Affinity Capture-Western), NTF4 (Co-localization), NTRK2 (PCA), NTRK2 (Reconstituted Complex), NTRK2 (Affinity Capture-Western), NDFIP1 (PCA), NTRK2 (Reconstituted Complex), NTRK2 (Affinity Capture-Western), NGFR (Affinity Capture-Western), ERBB4 (Affinity Capture-Western), NTRK2 (Affinity Capture-Western), NTRK2 (FRET), NTRK2 (Affinity Capture-Western), NTRK2 (Affinity Capture-Western)

ESM2 similar proteins: A4IGL7, D3ZB51, E9PZ19, O75882, O94779, O95970, P00533, P02469, P07942, P13590, P15209, P24503, P24786, P33150, P39038, P55245, P55283, P68500, P97300, P97527, P97546, Q01279, Q01973, Q03351, Q16288, Q16620, Q1EGL2, Q3B7N0, Q3UQ28, Q5IFJ9, Q5IS37, Q5IS82, Q5R945, Q63604, Q6IS24, Q6VNS1, Q7TPD3, Q7TT15, Q8K4Y5, Q8N475

Diamond homologs: A0M8R7, A0M8S8, A1X150, B3MH43, B3NS99, B4GBH0, B4HNW4, B4KPU0, B4MR28, B4P5Q9, B4QC63, O15146, O73798, P00529, P04629, P06213, P08069, P08581, P08922, P08941, P09208, P14616, P14617, P15127, P15208, P15209, P16056, P23049, P24062, P24786, P35739, P42159, P42681, P97523, Q00PJ8, Q01973, Q03146, Q03351, Q04912, Q05688

SIGNOR signaling

30 interactions.

A	Effect	B	Mechanism
NTRK2	down-regulates	KCNA3	phosphorylation
NTRK2	“up-regulates activity”	FRS3	phosphorylation
PTPN1	“down-regulates activity”	NTRK2	dephosphorylation
ASH1L	“up-regulates quantity by expression”	NTRK2	“transcriptional regulation”
PTPN11	“down-regulates activity”	NTRK2	dephosphorylation
NTRK2	“up-regulates activity”	PLCG1	phosphorylation
NTRK2	“up-regulates activity”	VAV2	phosphorylation
SRC	“up-regulates activity”	NTRK2	phosphorylation
BDNF	up-regulates	NTRK2	binding
NTF4	up-regulates	NTRK2	binding
NTRK2	up-regulates	SHC3	binding
NTRK2	up-regulates	FYN	binding
NTRK2	up-regulates	NCK2	binding
NTRK2	“up-regulates activity”	NTRK2	phosphorylation
NTRK2	unknown	NTRK2	phosphorylation
ANKRD11	“up-regulates quantity by expression”	NTRK2	“transcriptional regulation”
LSM-1231	“down-regulates activity”	NTRK2	“chemical inhibition”
RORA	“up-regulates quantity by expression”	NTRK2	“transcriptional regulation”
NTRK2	“up-regulates activity”	SHC3	phosphorylation

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — ANGS, CLLSLL, MBL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	7
Uncertain significance	390
Likely benign	349
Benign	40

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
2664671	NM_006180.6(NTRK2):c.970_986del (p.Leu324fs)	Pathogenic
2759466	NM_006180.6(NTRK2):c.173T>A (p.Leu58Ter)	Pathogenic
3632765	NM_006180.6(NTRK2):c.319del (p.Ala107fs)	Pathogenic
427213	NM_006180.6(NTRK2):c.1330G>T (p.Gly444Ter)	Pathogenic
487685	NM_006180.6(NTRK2):c.2159C>T (p.Thr720Ile)	Pathogenic
9127	NM_006180.6(NTRK2):c.2165A>G (p.Tyr722Cys)	Pathogenic
1319369	NM_006180.6(NTRK2):c.302C>A (p.Ser101Tyr)	Likely pathogenic
1388087	NM_006180.6(NTRK2):c.1765-1G>A	Likely pathogenic
1977550	NM_006180.6(NTRK2):c.1444+1G>A	Likely pathogenic
2056320	NM_006180.6(NTRK2):c.1397-1G>C	Likely pathogenic
3068732	NM_006180.6(NTRK2):c.1652G>A (p.Arg551Gln)	Likely pathogenic
3775287	NM_006180.6(NTRK2):c.720+1G>A	Likely pathogenic
983314	NM_006180.6(NTRK2):c.1279G>T (p.Gly427Cys)	Likely pathogenic

SpliceAI

4376 predictions. Top by Δscore:

Variant	Effect	Δscore
9:84702234:G:GG	donor_gain	1.0000
9:84702342:TCACA:T	acceptor_loss	1.0000
9:84702343:CACA:C	acceptor_loss	1.0000
9:84702344:ACAGG:A	acceptor_loss	1.0000
9:84702345:CA:C	acceptor_loss	1.0000
9:84702346:A:AG	acceptor_gain	1.0000
9:84702346:A:T	acceptor_loss	1.0000
9:84702346:AG:A	acceptor_gain	1.0000
9:84702347:G:GC	acceptor_loss	1.0000
9:84702347:G:GG	acceptor_gain	1.0000
9:84702347:GG:G	acceptor_gain	1.0000
9:84702347:GGAC:G	acceptor_gain	1.0000
9:84702347:GGACA:G	acceptor_gain	1.0000
9:84702415:CACAT:C	donor_gain	1.0000
9:84702416:ACAT:A	donor_gain	1.0000
9:84702416:ACATG:A	donor_loss	1.0000
9:84702417:CAT:C	donor_gain	1.0000
9:84702418:AT:A	donor_gain	1.0000
9:84702418:ATGT:A	donor_loss	1.0000
9:84702419:TGT:T	donor_loss	1.0000
9:84702420:G:GG	donor_gain	1.0000
9:84702420:GTA:G	donor_loss	1.0000
9:84702421:T:A	donor_loss	1.0000
9:84702422:AA:A	donor_loss	1.0000
9:84707842:A:AG	acceptor_gain	1.0000
9:84707843:G:GG	acceptor_gain	1.0000
9:84707843:GC:G	acceptor_gain	1.0000
9:84707843:GCA:G	acceptor_gain	1.0000
9:84707908:GAACT:G	donor_gain	1.0000
9:84707910:ACT:A	donor_gain	1.0000

AlphaMissense

5591 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:84727749:T:A	W317R	1.000
9:84727749:T:C	W317R	1.000
9:84727837:T:C	L346P	1.000
9:84727882:T:C	L361P	1.000
9:84934189:T:A	I538N	1.000
9:84934207:T:C	L544P	1.000
9:84934209:G:C	G545R	1.000
9:84934209:G:T	G545C	1.000
9:84934210:G:A	G545D	1.000
9:84934210:G:T	G545V	1.000
9:84934215:G:A	G547R	1.000
9:84934215:G:C	G547R	1.000
9:84934216:G:A	G547E	1.000
9:84934216:G:C	G547A	1.000
9:84934216:G:T	G547V	1.000
9:84934221:T:A	F549I	1.000
9:84934221:T:C	F549L	1.000
9:84934221:T:G	F549V	1.000
9:84934222:T:C	F549S	1.000
9:84934222:T:G	F549C	1.000
9:84934223:T:A	F549L	1.000
9:84934223:T:G	F549L	1.000
9:84934224:G:A	G550R	1.000
9:84934224:G:C	G550R	1.000
9:84934225:G:A	G550E	1.000
9:84934225:G:C	G550A	1.000
9:84934225:G:T	G550V	1.000
9:84934237:T:C	L554P	1.000
9:84934239:G:C	A555P	1.000
9:84934240:C:A	A555D	1.000

dbSNP variants (sampled 300 via entrez): RS1000005496 (9:84931005 AT>A,ATT), RS1000021269 (9:84674955 C>T), RS1000026023 (9:84915237 A>G), RS1000049496 (9:84668754 C>T), RS1000050491 (9:84976201 G>A,T), RS1000062229 (9:84826489 C>T), RS1000062622 (9:84698421 G>A,T), RS1000068778 (9:84758563 G>A), RS1000076418 (9:84852393 G>A), RS1000086306 (9:84720387 T>A,C), RS1000086649 (9:84962095 A>G), RS1000105974 (9:84744441 C>T), RS1000111841 (9:84799876 A>G), RS1000115272 (9:84839615 T>G), RS1000130941 (9:84833527 A>G)

Disease associations

OMIM: gene MIM:600456 | disease phenotypes: MIM:613886, MIM:617830, MIM:601665

GenCC curated gene-disease

Disease	Classification	Inheritance
obesity, hyperphagia, and developmental delay	Strong	Autosomal dominant
developmental and epileptic encephalopathy, 58	Strong	Autosomal dominant
infantile spasms	Supportive	Autosomal dominant
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant

Mondo (9): obesity, hyperphagia, and developmental delay (MONDO:0013483), developmental and epileptic encephalopathy, 58 (MONDO:0033367), intellectual disability (MONDO:0001071), autism spectrum disorder (MONDO:0005258), inherited obesity (MONDO:0019182), neuroblastoma (MONDO:0005072), obesity disorder (MONDO:0011122), infantile spasms (MONDO:0018097), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (6): Genetic obesity (Orphanet:77828), Neuroblastoma (Orphanet:635), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399)

HPO phenotypes

71 total (30 of 71 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000324	Facial asymmetry
HP:0000348	High forehead
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000707	Abnormality of the nervous system
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000750	Delayed speech and language development
HP:0000817	Reduced eye contact
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001264	Spastic diplegia
HP:0001265	Hyporeflexia
HP:0001268	Mental deterioration
HP:0001273	Abnormal corpus callosum morphology
HP:0001288	Gait disturbance

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST002499_1	Birth weight	1.000000e-08
GCST002541_72	Menarche (age at onset)	2.000000e-09
GCST002805_9	Body mass index	3.000000e-07
GCST004583_2	Waist-to-hip circumference ratio (recreational physical activity interaction)	9.000000e-06
GCST004904_62	Body mass index	1.000000e-08
GCST004904_81	Body mass index	1.000000e-09
GCST005648_5	Serum metabolite concentrations in chronic kidney disease	3.000000e-09
GCST008833_9	Type 2 diabetes	2.000000e-07
GCST009575_2	Lifetime anxiety disorder	7.000000e-09
GCST010002_322	Refractive error	6.000000e-10
GCST010273_4	Gout (normal type)	3.000000e-08
GCST010989_150	Body size at age 10	2.000000e-08
GCST011037_7	Parkinson’s disease progression (cognitive)	6.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight
EFO:0004703	age at menarche
EFO:0005937	longitudinal BMI measurement
EFO:0004343	waist-hip ratio
EFO:0004340	body mass index
EFO:0009819	comparative body size at age 10, self-reported
EFO:0008336	disease progression measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009447	Neuroblastoma	C04.557.465.625.600.590.650.550; C04.557.470.670.590.650.550; C04.557.580.625.600.590.650.550
C563938	Obesity, Hyperphagia, and Developmental Delay (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3559684 (PROTEIN FAMILY), CHEMBL4523622 (PROTEIN FAMILY), CHEMBL4898 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

50 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 292,668 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	285
CHEMBL1852688	INFIGRATINIB	4	2,209
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3286830	LORLATINIB	4	3,598
CHEMBL3889654	LAROTRECTINIB	4	1,850
CHEMBL3989939	LAROTRECTINIB SULFATE	4	771
CHEMBL4298138	REPOTRECTINIB	4	1,038
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL3137331	DEFACTINIB	3	1,229
CHEMBL3989926	SITRAVATINIB	3
CHEMBL4297190	SURUFATINIB	3
CHEMBL483158	ALISERTIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL103667	DORAMAPIMOD	2
CHEMBL1230609	FORETINIB	2
CHEMBL124660	TANDUTINIB	2
CHEMBL1721885	SU-014813	2
CHEMBL1738757	REBASTINIB	2

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
NTRK1 Amplification OR NTRK3 Amplification OR NTRK2 Amplification	Entrectinib	Cancer	Sensitivity/Response	CIViC B	EID2958

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

PharmGKB clinical annotations

10 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10465180	Efficacy	3	clozapine	Schizophrenia
rs1387923	Efficacy	4	lithium	Bipolar Disorder
rs1439050	Toxicity	3	antidepressants	Major Depressive Disorder
rs1778929	Efficacy	3	clozapine	Schizophrenia
rs1948308	Dosage	3	methadone	Heroin Dependence;Opioid-Related Disorders
rs2120266	Dosage	3	methadone	Heroin Dependence;Opioid-Related Disorders
rs2289658	Dosage	3	methadone	Heroin Dependence;Opioid-Related Disorders
rs2378676	Dosage	3	methadone	Heroin Dependence;Opioid-Related Disorders
rs4358872	Dosage	3	methadone	Heroin Dependence;Opioid-Related Disorders
rs4877900	Dosage	3	methadone	Heroin Dependence;Opioid-Related Disorders

PharmGKB variants

23 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1187326	NTRK2		0.00	0
rs1187327	NTRK2		0.00	0
rs1387923	NTRK2	4	-1.75	1	lithium
rs1565445	NTRK2		0.00	0
rs1778929	NTRK2	3	0.00	1	clozapine
rs1948308	NTRK2	3	0.00	1	methadone
rs2120266	NTRK2	3	0.00	1	methadone
rs2289656	NTRK2		0.00	0
rs2289658	NTRK2	3	0.00	1	methadone
rs2378676	NTRK2	3	0.00	1	methadone
rs4358872	NTRK2	3	0.00	1	methadone
rs4877900	NTRK2	3	0.00	1	methadone
rs10465180	NTRK2	3	3.50	1	clozapine
rs1439050	NTRK2	3	2.25	1	antidepressants
rs1147198	NTRK2		0.00	0
rs1187286	NTRK2		0.00	0
rs1867283	NTRK2		0.00	0
rs10868235	NTRK2		0.00	0
rs11140800	NTRK2		0.00	0
rs1187352	NTRK2		0.00	0
rs1778933	NTRK2		0.00	0
rs2289657	NTRK2		0.00	0
rs3824519	NTRK2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Type VII RTKs: Neurotrophin receptor/Trk family

Most potent curated ligand interactions (17 total), top 17:

Ligand	Action	Affinity	Parameter
GR-389988	Inhibition	10.0	pIC50
zurletrectinib	Inhibition	9.84	pIC50
repotrectinib	Inhibition	9.52	pIC50
eratrectinib	Inhibition	9.24	pIC50
emzeltrectinib	Inhibition	9.0	pIC50
CH7057288	Inhibition	8.7	pIC50
taletrectinib	Inhibition	8.64	pIC50
DZX19	Inhibition	8.64	pIC50
selitrectinib	Inhibition	8.49	pIC50
compound 8e [PMID: 24432909]	Inhibition	8.4	pIC50
AZD1332	Inhibition	8.3	pIC50
CEP-11981	Inhibition	8.3	pIC50
RIPK1 inhibitor 22b	Inhibition	8.1	pIC50
GNF-5837	Inhibition	8.05	pIC50
DDR1/2 inhibitor 5n	Inhibition	7.96	pKd
GW-2580	Inhibition	7.44	pKd
MK-2461	Inhibition	7.21	pIC50

Binding affinities (BindingDB)

120 measured of 163 human assays (163 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-[[3-methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]methyl]-6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridin-2-amine	IC50	0.1 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
6-(6-dimethylphosphoryl-3-pyridinyl)-3-[[3-methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]methyl]imidazo[4,5-b]pyridin-2-amine	IC50	0.2 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[[3-methoxy-4-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]phenyl]methyl]-6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridin-2-amine	IC50	0.2 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[[4-[(6-cyclopropyl-3-pyridinyl)methoxy]-3-methoxyphenyl]methyl]-6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridin-2-amine	IC50	0.2 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[[3-methoxy-4-[(2-methyl-1,3-thiazol-4-yl)methoxy]phenyl]methyl]-6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridin-2-amine	IC50	0.2 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[[3-methoxy-4-[[4-(trifluoromethoxy)phenyl]methoxy]phenyl]methyl]-6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridin-2-amine	IC50	0.2 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[[3-methoxy-4-[(6-propan-2-yl-3-pyridinyl)methoxy]phenyl]methyl]-6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridin-2-amine	IC50	0.2 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[[3-methoxy-4-[[2-(trifluoromethyl)-1,3-thiazol-4-yl]methoxy]phenyl]methyl]-6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridin-2-amine	IC50	0.2 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[[3-methoxy-4-[(6-methoxy-3-pyridinyl)methoxy]phenyl]methyl]-6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridin-2-amine	IC50	0.3 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[[3-methoxy-4-[[4-(trifluoromethyl)phenyl]methoxy]phenyl]methyl]-6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridin-2-amine	IC50	0.3 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[[3-methoxy-4-[[4-(2,2,2-trifluoroethyl)phenyl]methoxy]phenyl]methyl]-6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridin-2-amine	IC50	0.3 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
1-[[3-methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]methyl]-5-(1-methylpyrazol-4-yl)benzimidazol-2-amine	IC50	0.5 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[[3-methoxy-4-[(6-methyl-3-pyridinyl)methoxy]phenyl]methyl]-6-(1-piperidin-4-ylpyrazol-4-yl)imidazo[4,5-b]pyridine	IC50	0.6 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[[3-methoxy-4-[[4-(1,1,2,2,2-pentafluoroethyl)phenyl]methoxy]phenyl]methyl]-6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridin-2-amine	IC50	0.6 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[[3-methoxy-4-[[4-(trifluoromethylsulfanyl)phenyl]methoxy]phenyl]methyl]-6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridin-2-amine	IC50	0.6 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[(1S)-1-[3-methoxy-4-[[4-(trifluoromethyl)phenyl]methoxy]phenyl]ethyl]-6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridin-2-amine	IC50	0.6 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[1-[3-methoxy-4-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]phenyl]ethyl]-6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridin-2-amine	IC50	0.6 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[1-[3-methoxy-4-[[4-(trifluoromethyl)phenyl]methoxy]phenyl]ethyl]-6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridin-2-amine	IC50	0.6 nM	US-9611265: Tropomyosin-related kinase (TRK) inhibitors
2-[4-[2-amino-3-[1-[3-methoxy-4-[[4-(trifluoromethyl)phenyl]methoxy]phenyl]ethyl]imidazo[4,5-b]pyridin-6-yl]pyrazol-1-yl]ethanol	IC50	0.6 nM	US-9611265: Tropomyosin-related kinase (TRK) inhibitors
3-[[3-methoxy-4-[(6-methoxy-3-pyridinyl)methoxy]phenyl]methyl]-6-pyridin-4-ylimidazo[4,5-b]pyridin-2-amine	IC50	0.7 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[[3-methoxy-4-[(6-methoxy-3-pyridinyl)methoxy]phenyl]methyl]-6-(1-piperidin-4-ylpyrazol-4-yl)imidazo[4,5-b]pyridine	IC50	0.9 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
1-[[3-methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]methyl]-5-[1-(2-morpholin-4-ylethyl)pyrazol-4-yl]benzimidazol-2-amine	IC50	1 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
1-[1-[3-methoxy-4-[(6-methoxy-3-pyridinyl)methoxy]phenyl]ethyl]-5-(1-methylpyrazol-4-yl)benzimidazol-2-amine	IC50	1 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[1-[3-methoxy-4-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]phenyl]ethyl]-6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridine	IC50	1 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
4-[2-amino-3-[1-[3-methoxy-4-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]phenyl]ethyl]imidazo[4,5-b]pyridin-6-yl]but-3-yn-1-ol	IC50	1 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[1-[3-methoxy-4-[[4-(trifluoromethyl)phenyl]methoxy]phenyl]ethyl]-6-(1H-pyrazol-4-yl)imidazo[4,5-b]pyridin-2-amine	IC50	1 nM	US-9611265: Tropomyosin-related kinase (TRK) inhibitors
(2-(6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-indazol-3-yl)-4,6-dihydropyrrolo[3,4-d]imidazol-5(1H)-yl) (3-hydroxyazetidin-1-yl)ketone	IC50	1.04 nM	US-20250387388: COMPOUND AS TRK INHIBITOR AND/OR RET INHIBITOR AND USE THEREOF
(2-(6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-indazol-3-yl)-4,6-dihydropyrrolo[3,4-d]imidazol-5(1H)-yl)(4-ethylpiperazin-1-yl)ketone	IC50	1.06 nM	US-20250387388: COMPOUND AS TRK INHIBITOR AND/OR RET INHIBITOR AND USE THEREOF
3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	IC50	1.18 nM	US-8822500: Tyrosine kinase inhibitors
(2-(6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-indazol-3-yl)-4,6-dihydropyrrolo[3,4-d]imidazol-5(1H)-yl)(morpholino)ketone	IC50	1.27 nM	US-20250387388: COMPOUND AS TRK INHIBITOR AND/OR RET INHIBITOR AND USE THEREOF
(2-(6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-indazol-3-yl)-4,6-dihydropyrrolo[3,4-d]imidazol-5(1H)-yl)(4-methylpiperazin-1-yl)ketone	IC50	1.39 nM	US-20250387388: COMPOUND AS TRK INHIBITOR AND/OR RET INHIBITOR AND USE THEREOF
Staurosporine	KD	1.7 nM
(S)-(2-(6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-indazol-3-yl)-4,6-dihydropyrrolo[3,4-d]imidazol-5(1H)-yl)(3-hydroxylpyrrolidin-1-yl)ketone	IC50	1.77 nM	US-20250387388: COMPOUND AS TRK INHIBITOR AND/OR RET INHIBITOR AND USE THEREOF
3-[[3-methoxy-4-[(6-methoxy-3-pyridinyl)methoxy]phenyl]methyl]-6-(1-methylpyrazol-3-yl)imidazo[4,5-b]pyridin-2-amine	IC50	2 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[[3-methoxy-4-[(6-methoxy-3-pyridinyl)methoxy]phenyl]methyl]-6-pyridin-3-ylimidazo[4,5-b]pyridin-2-amine	IC50	2 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[[3-methoxy-4-[(6-methoxy-3-pyridinyl)methoxy]phenyl]methyl]-6-pyridin-2-ylimidazo[4,5-b]pyridin-2-amine	IC50	2 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
6-[2-(dimethylamino)ethyl]-2-[2-oxo-4-[[(2S)-1-(2,3,5,6-tetrafluorophenyl)propan-2-yl]amino]piperidin-3-yl]-3,5-dihydropyrrolo[3,4-f]benzimidazol-7-one	IC50	2.06 nM	US-8822500: Tyrosine kinase inhibitors
2-(6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-indazol-3-yl)-N,N-dimethyl-4,6-dihydropyrrolo[3,4-d]imidazol-5(1H)-carboxamide	IC50	2.93 nM	US-20250387388: COMPOUND AS TRK INHIBITOR AND/OR RET INHIBITOR AND USE THEREOF
4-[2-amino-3-[[3-methoxy-4-[(6-methoxy-3-pyridinyl)methoxy]phenyl]methyl]imidazo[4,5-b]pyridin-6-yl]but-3-yn-1-ol	IC50	3 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[(1R)-1-[3-methoxy-4-[[4-(trifluoromethyl)phenyl]methoxy]phenyl]ethyl]-6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridin-2-amine	IC50	3 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
(2-(6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-indazol-3-yl)-4,6-dihydropyrrolo[3,4-d]imidazol-5(1H)-yl)(4-hydroxylpiperidin-1-yl)ketone	IC50	3.37 nM	US-20250387388: COMPOUND AS TRK INHIBITOR AND/OR RET INHIBITOR AND USE THEREOF
6-(1-methylpiperidin-4-yl)-2-[2-oxo-4-[[(2S)-1-(2,3,5,6-tetrafluorophenyl)propan-2-yl]amino]piperidin-3-yl]-3,5-dihydropyrrolo[3,4-f]benzimidazol-7-one	IC50	3.48 nM	US-8822500: Tyrosine kinase inhibitors
2-(6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-indazol-3-yl)-N-(2-hydroxylethyl)-4,6-dihydropyrrolo[3,4-d]imidazol-5(1H)-carboxamide	IC50	3.58 nM	US-20250387388: COMPOUND AS TRK INHIBITOR AND/OR RET INHIBITOR AND USE THEREOF
1-[[3-methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]methyl]-5-pyridin-4-ylbenzimidazol-2-amine	IC50	4 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[[3-methoxy-4-[(6-methoxy-3-pyridinyl)methoxy]phenyl]methyl]-6-phenylimidazo[4,5-b]pyridin-2-amine	IC50	4 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
6-(4-fluorophenyl)-3-[[3-methoxy-4-[(6-methoxy-3-pyridinyl)methoxy]phenyl]methyl]imidazo[4,5-b]pyridin-2-amine	IC50	4 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
4-[3-[[4-[[6-(difluoromethyl)-3-pyridinyl]methoxy]-3-methoxyphenyl]methyl]imidazo[4,5-b]pyridin-6-yl]but-3-yn-1-ol	IC50	4 nM	US-9067914: Tropomyosin-related kinase (TRK) inhibitors
3-[1-[3-methoxy-4-[[6-(trifluoromethyl)-3-pyridinyl]methoxy]phenyl]propyl]-6-(1-methylpyrazol-4-yl)imidazo[4,5-b]pyridin-2-amine	IC50	4 nM	US-9611265: Tropomyosin-related kinase (TRK) inhibitors
cyclopropyl (2-(6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-indazol-3-yl)pyrrolo[3,4-d]imidazol-5(1H, 4H,6H)-yl)ketone	IC50	4.16 nM	US-20250387388: COMPOUND AS TRK INHIBITOR AND/OR RET INHIBITOR AND USE THEREOF

ChEMBL bioactivities

1077 potent at pChembl≥5 of 1190 total, top 39 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.30	IC50	0.05	nM	REPOTRECTINIB
10.20	IC50	0.0636	nM	STAUROSPORINE
10.03	IC50	0.093	nM	STAUROSPORINE
10.00	IC50	0.1	nM	GZ-389988
9.95	IC50	0.112	nM	STAUROSPORINE
9.74	Kd	0.18	nM	CHEMBL6044141
9.70	IC50	0.2	nM	CHEMBL3673453
9.70	IC50	0.2	nM	CHEMBL3673477
9.70	IC50	0.2	nM	CHEMBL3673479
9.70	IC50	0.2	nM	CHEMBL3673480
9.70	IC50	0.2	nM	CHEMBL3678283
9.70	IC50	0.2	nM	CHEMBL3678285
9.70	IC50	0.2	nM	CHEMBL3678287
9.70	IC50	0.2	nM	CHEMBL4555442
9.52	IC50	0.3	nM	CHEMBL3673436
9.52	IC50	0.3	nM	CHEMBL3673476
9.52	IC50	0.3	nM	CHEMBL3673478
9.52	IC50	0.3	nM	CHEMBL3678286
9.48	IC50	0.33	nM	LAROTRECTINIB
9.40	Ki	0.4	nM	CHEMBL3286829
9.40	IC50	0.4	nM	LAROTRECTINIB
9.34	IC50	0.46	nM	LAROTRECTINIB
9.30	Ki	0.5	nM	CHEMBL3286820
9.30	IC50	0.5	nM	CHEMBL3673436
9.27	IC50	0.54	nM	LAROTRECTINIB
9.22	IC50	0.6	nM	CHEMBL3673463
9.22	IC50	0.6	nM	CHEMBL3673489
9.22	IC50	0.6	nM	CHEMBL3678284
9.22	IC50	0.6	nM	CHEMBL3678297
9.22	IC50	0.6	nM	CHEMBL3678300
9.22	IC50	0.6	nM	CHEMBL5770922
9.22	IC50	0.6	nM	CHEMBL5855234
9.20	IC50	0.63	nM	LAROTRECTINIB
9.15	IC50	0.7	nM	CHEMBL3673486
9.15	IC50	0.71	nM	CHEMBL4794404
9.13	IC50	0.74	nM	ENTRECTINIB
9.10	Ki	0.7943	nM	CHEMBL1980995
9.05	IC50	0.9	nM	CHEMBL3673462
9.03	IC50	0.93	nM	CHEMBL457614

PubChem BioAssay actives

485 with measured affinity, of 2494 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
Repotrectinib	1812886: Inhibition of human TRKB using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay	ic50	0.0001	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1531913: Inhibition of human TRKB using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay	ic50	0.0001	uM
N-[(5-fluoro-2-methylsulfonylphenyl)methyl]-3-(1-methylpyrazol-4-yl)-1H-indazol-5-amine	1552242: Inhibition of human GST-tagged TRKB (456 to 822) expressed in baculovirus expression system using TK-biotin peptide as substrate incubated for 45 min by TR-FRET assay	ic50	0.0002	uM
1-[[3-methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]methyl]-5-(1-methylpyrazol-4-yl)benzimidazol-2-amine	1322470: Inhibition of N-terminal GST tagged human TrkB cytoplasmic domain (456 to 822 amino acids) pre-incubated for 15 mins before peptide substrate addition for 180 mins by fluorescence based assay	ic50	0.0003	uM
(16R)-19-amino-3-cyclopropyl-13-fluoro-5,8,16-trimethyl-17-oxa-4,5,8,20-tetrazatetracyclo[16.3.1.02,6.010,15]docosa-1(22),2(6),3,10(15),11,13,18,20-octaen-9-one	1153101: Inhibition of TRKB (unknown origin) by off-chip mobility shift assay	ki	0.0004	uM
(16R)-19-amino-13-fluoro-3,5,8,16-tetramethyl-17-oxa-4,5,8,20-tetrazatetracyclo[16.3.1.02,6.010,15]docosa-1(22),2(6),3,10(15),11,13,18,20-octaen-9-one	1153101: Inhibition of TRKB (unknown origin) by off-chip mobility shift assay	ki	0.0005	uM
2-(4-methylpiperazin-1-yl)-N-[4-methyl-5-[3-[(E)-2-pyridin-2-ylethenyl]-1H-indazol-6-yl]-1,3-thiazol-2-yl]acetamide	1743349: Inhibition of human TRKB by Z-LYTE or ADP-Glo assay	ic50	0.0007	uM
5-chloro-2-N-[(1S)-1-(5-fluoro-2-pyridinyl)ethyl]-4-N-(3-propan-2-yloxy-1H-pyrazol-5-yl)pyrimidine-2,4-diamine	1546234: Inhibition of wild type human N-terminal GST-fusion tagged TRKB kinase domain (456 to 822 residues) expressed in baculovirus expression system by HTRF assay	ic50	0.0009	uM
6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]-3-pyridin-2-ylimidazo[1,2-b]pyridazine	1229325: Inhibition of Tel-fused TRKB (unknown origin) overexpressed in mouse BA/F3 cells assessed as inhibition of cell proliferation after 48 hrs by luciferase reporter gene assay in absence of recombinant mouse IL3	ic50	0.0010	uM
2-[4-[4-[6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl]-2-pyridinyl]piperazin-1-yl]acetic acid	1229325: Inhibition of Tel-fused TRKB (unknown origin) overexpressed in mouse BA/F3 cells assessed as inhibition of cell proliferation after 48 hrs by luciferase reporter gene assay in absence of recombinant mouse IL3	ic50	0.0010	uM
(6R,15R)-9-fluoro-15-methyl-2,11,16,20,21,24-hexazapentacyclo[16.5.2.02,6.07,12.021,25]pentacosa-1(24),7(12),8,10,18(25),19,22-heptaen-17-one	1812753: Inhibition of wild-type TrKB (unknown origin)	ic50	0.0010	uM
1-[3-(4-amino-7-propan-2-ylpyrrolo[2,1-f][1,2,4]triazine-5-carbonyl)phenyl]-3-(2,4-dichlorophenyl)urea	1551956: Inhibition of TRKB (unknown origin)	ic50	0.0010	uM
1-[3-tert-butyl-1-(4-chlorophenyl)pyrazol-5-yl]-3-[4-[(6,6-dimethyl-7-oxo-8H-pyrimido[5,4-b][1,4]oxazin-4-yl)amino]-3-methylphenyl]urea	1822433: Binding affinity to TrkB (unknown origin) assessed as inhibition constant by radiometric assay	ki	0.0010	uM
1-[3-(4-amino-7-propan-2-ylpyrrolo[2,1-f][1,2,4]triazine-5-carbonyl)phenyl]-3-phenylurea	1551956: Inhibition of TRKB (unknown origin)	ic50	0.0010	uM
1-[3-(4-amino-7-propan-2-ylpyrrolo[2,1-f][1,2,4]triazine-5-carbonyl)phenyl]-3-(4-phenylmethoxyphenyl)urea	1551956: Inhibition of TRKB (unknown origin)	ic50	0.0010	uM
1-[3-(4-amino-7-propan-2-ylpyrrolo[2,1-f][1,2,4]triazine-5-carbonyl)phenyl]-3-naphthalen-2-ylurea	1551956: Inhibition of TRKB (unknown origin)	ic50	0.0010	uM
Entrectinib	1878094: Inhibition of TrkB (unknown origin)	ic50	0.0010	uM
Larotrectinib	2007342: Inhibition of TRKB (unknown origin)	ic50	0.0010	uM
N-[5-amino-1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-5-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-2-methylbenzamide	578743: inhibition of TRKB	ic50	0.0010	uM
1-[3-[4-amino-7-[3-(dimethylamino)propyl]pyrrolo[2,1-f][1,2,4]triazine-5-carbonyl]phenyl]-3-(2,4-dichlorophenyl)urea	1551956: Inhibition of TRKB (unknown origin)	ic50	0.0010	uM
N-benzyl-3-[(E)-2-pyridin-2-ylethenyl]-2H-indazol-5-amine	1741213: Inhibition of TrkB (unknown origin) using Tyr1 peptide as substrate in presence of ATP measured after 2 hrs by FRET-based Z-Lyte kinase assay	ic50	0.0011	uM
5-[(3,5-difluorophenyl)methoxy]-3-[(E)-2-pyridin-2-ylethenyl]-1H-indazole	1741213: Inhibition of TrkB (unknown origin) using Tyr1 peptide as substrate in presence of ATP measured after 2 hrs by FRET-based Z-Lyte kinase assay	ic50	0.0012	uM
5-[(3,5-difluorophenyl)methyl]-3-[(E)-2-pyridin-2-ylethenyl]-2H-indazole	1741213: Inhibition of TrkB (unknown origin) using Tyr1 peptide as substrate in presence of ATP measured after 2 hrs by FRET-based Z-Lyte kinase assay	ic50	0.0013	uM
N-(3-tert-butyl-1-phenylpyrazol-5-yl)-2-(1-phenyltetrazol-5-yl)sulfanylacetamide	1601003: Binding affinity to recombinant human biotinylated and N-terminal DYKDDDDK-tagged TrkB kinase domain (456-822 residues) expressed in sf21 cells assessed as equilibrium constant by SPR based single cycle kinetics analysis	kd	0.0017	uM
1-(3-chlorophenyl)-3-[5-[2-[[7-[3-(dimethylamino)propoxy]quinazolin-4-yl]amino]ethyl]-1,3-thiazol-2-yl]urea	1829850: Inhibition of TRKB (unknown origin)	ic50	0.0018	uM
Crizotinib	617337: Inhibition of TRKB	ic50	0.0020	uM
N-[5-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidine-5-carbonyl)-3-pyridinyl]-2-(4-chlorophenyl)acetamide	1686375: Inhibition of human TrkB expressed in human U2OS cells pre-incubated 30 mins before neurotrophin addition and measured after 2 hrs by luminescence based assay	ic50	0.0020	uM
N-tert-butyl-2-[2-[8-(methanesulfonamido)-6,6-dimethyl-11-oxonaphtho[2,3-b][1]benzofuran-3-yl]ethynyl]-6-methylpyridine-4-carboxamide	1864433: Inhibition of TRKB (unknown origin)	ic50	0.0020	uM
5-fluoro-3-[(3E)-3-(2-piperazin-1-ylethoxyimino)indol-2-yl]-1H-indol-2-ol;hydrochloride	1737398: Inhibition of human TrkB in presence of ATP	ic50	0.0020	uM
1-[3-tert-butyl-1-(4-chlorophenyl)pyrazol-5-yl]-3-[4-[(2,2-dimethyl-3-oxo-4H-1,4-benzoxazin-8-yl)amino]-3-methylphenyl]urea	2139995: Inhibition of TRKB (unknown origin) by TR-FRET assay	ic50	0.0020	uM
N-[5-[2-amino-7-(1-hydroxy-2-methylpropan-2-yl)pyrrolo[2,3-d]pyrimidine-5-carbonyl]-3-pyridinyl]-2-(4-chlorophenyl)acetamide	1686375: Inhibition of human TrkB expressed in human U2OS cells pre-incubated 30 mins before neurotrophin addition and measured after 2 hrs by luminescence based assay	ic50	0.0020	uM
N-[5-(2-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidine-5-carbonyl)-3-pyridinyl]-2-(4-chlorophenyl)acetamide	1686375: Inhibition of human TrkB expressed in human U2OS cells pre-incubated 30 mins before neurotrophin addition and measured after 2 hrs by luminescence based assay	ic50	0.0020	uM
3-[5-[[(1R)-1-(2,5-difluorophenyl)ethyl]-methylamino]pyrazolo[1,5-a]pyrimidin-3-yl]-1,1-di(propan-2-yl)urea	1683516: Inhibition of Trk-B (unknown origin)	ic50	0.0024	uM
2-[(3R,4S)-3-fluoro-1-[2-[4-(trifluoromethoxy)phenyl]acetyl]piperidin-4-yl]oxy-5-(1-methylimidazol-4-yl)pyridine-3-carboxamide	1381368: Antagonist activity at prolink-tagged TrkB in human U2OS cells assessed as inhibition of BDNF-induced receptor phosphorylation by measuring reduction in EA-tagged SH2 protein recruitment preincubated for 30 mins followed by BDNF stimulation measured after 2 hrs by PathHunter enzyme complementation assay	ic50	0.0026	uM
6-(1-methylpyrazol-4-yl)-3-[(3R)-1-[2-[4-(trifluoromethoxy)phenyl]acetyl]pyrrolidin-3-yl]oxypyridine-2-carboxamide	1381368: Antagonist activity at prolink-tagged TrkB in human U2OS cells assessed as inhibition of BDNF-induced receptor phosphorylation by measuring reduction in EA-tagged SH2 protein recruitment preincubated for 30 mins followed by BDNF stimulation measured after 2 hrs by PathHunter enzyme complementation assay	ic50	0.0027	uM
(3R)-N-[5-[(2S)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide	1883889: Inhibition of N-terminal human TRKB (456 to 822 residues) expressed in baculovirus expression system using TK as substrate measured after 40 mins in presence of ATP by HTRF assay	ic50	0.0029	uM
N-[(1R)-1-(3,5-difluorophenyl)ethyl]-3-[(E)-2-pyridin-2-ylethenyl]-2H-indazol-5-amine	1741213: Inhibition of TrkB (unknown origin) using Tyr1 peptide as substrate in presence of ATP measured after 2 hrs by FRET-based Z-Lyte kinase assay	ic50	0.0029	uM
1-(3-tert-butyl-1-phenylpyrazol-5-yl)-3-[4-[(6,6-dimethyl-7-oxo-8H-pyrimido[5,4-b][1,4]oxazin-4-yl)amino]-3-methylphenyl]urea	1822410: Inhibition of wild type TrkB (unknown origin) using poly(Glu: Tyr) as substrate preincubated for 15 mins followed by substrate addition and further incubated for 30 mins in presence of [gamma-33P]ATP by scintillation counting method	ic50	0.0030	uM
4-fluoro-N-[6-[[4-(2-hydroxypropan-2-yl)piperidin-1-yl]methyl]-1-[4-(propan-2-ylcarbamoyl)cyclohexyl]benzimidazol-2-yl]benzamide	1533333: Inhibition of TRKB (unknown origin)	ic50	0.0030	uM
(3S)-N-[5-[[(1R)-1-(2,5-difluorophenyl)ethyl]amino]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide	1683516: Inhibition of Trk-B (unknown origin)	ic50	0.0031	uM
1-[5-[[(1R)-1-(2,5-difluorophenyl)ethyl]-methylamino]pyrazolo[1,5-a]pyrimidin-3-yl]-3-(4-hydroxyphenyl)urea	1683516: Inhibition of Trk-B (unknown origin)	ic50	0.0031	uM
3,5-difluoro-N-[[3-[(E)-2-pyridin-2-ylethenyl]-2H-indazol-5-yl]methyl]aniline	1741213: Inhibition of TrkB (unknown origin) using Tyr1 peptide as substrate in presence of ATP measured after 2 hrs by FRET-based Z-Lyte kinase assay	ic50	0.0035	uM
(3Z)-3-[(5-methoxy-1-methylindol-3-yl)methylidene]-2-oxo-1H-indole-5-sulfonamide	1734314: Inhibition of TrkB (unknown origin)	ic50	0.0039	uM
1-[4-[6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl]-2-pyridinyl]piperidin-4-ol	1229325: Inhibition of Tel-fused TRKB (unknown origin) overexpressed in mouse BA/F3 cells assessed as inhibition of cell proliferation after 48 hrs by luciferase reporter gene assay in absence of recombinant mouse IL3	ic50	0.0040	uM
5-(3,5-difluorophenoxy)-3-[(E)-2-pyridin-2-ylethenyl]-1H-indazole	1741213: Inhibition of TrkB (unknown origin) using Tyr1 peptide as substrate in presence of ATP measured after 2 hrs by FRET-based Z-Lyte kinase assay	ic50	0.0040	uM
(2S)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N-(6-fluoro-3-pyridinyl)-2-methylpyrrolidine-2-carboxamide	1533333: Inhibition of TRKB (unknown origin)	ic50	0.0040	uM
1-[6-[6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl]-2-pyridinyl]piperidin-4-ol	1229325: Inhibition of Tel-fused TRKB (unknown origin) overexpressed in mouse BA/F3 cells assessed as inhibition of cell proliferation after 48 hrs by luciferase reporter gene assay in absence of recombinant mouse IL3	ic50	0.0040	uM
N-[5-[2-amino-7-(1-hydroxy-2-methylpropan-2-yl)pyrrolo[2,3-d]pyrimidine-5-carbonyl]-3-pyridinyl]-2-(5-chloro-2-pyridinyl)acetamide	1686375: Inhibition of human TrkB expressed in human U2OS cells pre-incubated 30 mins before neurotrophin addition and measured after 2 hrs by luminescence based assay	ic50	0.0040	uM
(2R)-2-[5-[6-amino-5-[(1R)-1-[5-fluoro-2-(triazol-2-yl)phenyl]ethoxy]-3-pyridinyl]-4-methyl-1,3-thiazol-2-yl]propane-1,2-diol	1074704: Inhibition of NTRK2 (unknown origin) using Km levels of ATP	ic50	0.0040	uM
2-(4-chlorophenyl)-N-[5-(7-propan-2-ylpyrrolo[2,3-d]pyrimidine-5-carbonyl)-3-pyridinyl]acetamide	1686375: Inhibition of human TrkB expressed in human U2OS cells pre-incubated 30 mins before neurotrophin addition and measured after 2 hrs by luminescence based assay	ic50	0.0040	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	affects cotreatment, increases expression	6
Arsenic Trioxide	increases sumoylation, decreases expression, increases expression	5
(+)-JQ1 compound	decreases expression, increases expression	3
Dronabinol	increases expression	3
Valproic Acid	affects cotreatment, increases expression	3
bisphenol A	increases expression, increases methylation	2
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	2
staurosporine aglycone	affects cotreatment, decreases response to substance, decreases phosphorylation, affects binding, decreases activity (+2 more)	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Cocaine	decreases expression	2
Doxorubicin	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Acrylamide	decreases expression	2
bisphenol F	affects cotreatment, increases expression	1
deoxynivalenol	decreases expression	1
sulforaphane	decreases reaction, increases expression, decreases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	decreases methylation	1
tetrachlorodian	decreases expression	1
methyllycaconitine	decreases reaction, increases expression	1
echinacoside	decreases reaction, decreases phosphorylation	1
tamibarotene	increases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, decreases expression	1
ginsenoside Rg3	decreases reaction, decreases response to substance, affects binding, affects cotreatment, decreases activity (+1 more)	1
perfluoro-n-nonanoic acid	increases phosphorylation	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
6,7-dihydroxyflavone	decreases expression, decreases reaction	1
dorsomorphin	increases expression, affects cotreatment	1

ChEMBL screening assays

554 unique, capped per target: 547 binding, 5 admet, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4349470	Binding	Inhibition of TRKA/TRKB (unknown origin)	Targeting tropomyosin receptor kinase for cancer therapy. — Eur J Med Chem
CHEMBL1963832	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: NTRK2	PubChem BioAssay data set
CHEMBL3997038	ADMET	Inhibition of recombinant human TrkB expressed in DHFR deficient CHO cells assessed as inhibition of human brain-derived neurotrophic factor-induced calcium influx by Fluo-4 AM dye based assay	The juxtamembrane region of TrkA kinase is critical for inhibitor selectivity. — Bioorg Med Chem Lett

Cellosaurus cell lines

12 cell lines: 7 cancer cell line, 3 factor-dependent cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_9868	HEK-293-TrkB	Transformed cell line	Female
CVCL_B1ZA	Abcam HeLa NTRK2 KO	Cancer cell line	Female
CVCL_B8LR	Abcam HCT 116 NTRK2 KO	Cancer cell line	Male
CVCL_B9NW	Abcam A-549 NTRK2 KO	Cancer cell line	Male
CVCL_D1TT	Abcam U-87MG NTRK2 KO	Cancer cell line	Male
CVCL_D2GR	Abcam MCF-7 NTRK2 KO	Cancer cell line	Female
CVCL_KB40	CellSensor TrkB-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female
CVCL_UE74	Ba/F3 ETV6-NTRK2	Factor-dependent cell line
CVCL_UE75	Ba/F3 ETV6-NTRK2-G709C	Factor-dependent cell line
CVCL_UE76	Ba/F3 ETV6-NTRK2-G639R	Factor-dependent cell line

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01413711	PHASE4	WITHDRAWN	An Open-Label, Single and Multiple Oral Dose Pharmacokinetic Study of Vigabatrin in Infants With Infantile Spasms
NCT02092883	PHASE4	COMPLETED	Evaluation of Neuroinflammation in Children With Infantile Spasms
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01575639	PHASE3	COMPLETED	Prednisolone in Infantile Spasms- High Dose Versus Usual Dose
NCT01828437	PHASE3	COMPLETED	Addition of Pyridoxine to Prednisolone in Infantile Spasms
NCT02299115	PHASE3	WITHDRAWN	Prednisolone Versus Vigabatrin in the First-line Treatment of Infantile Spasms
NCT02953548	PHASE3	COMPLETED	Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms (GWPCARE7)
NCT02954887	PHASE3	COMPLETED	Phase 3 Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms: Open-label Extension Phase (GWPCARE7)
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension