Gene Report

Basic information

Related studies

Functional annotation

Related other genetic factors

Overlap with SZ and MDD

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Basic Info

Approved Symbol	NTRK2
Symbol Alias	TRKB
Approved Name	neurotrophic tyrosine kinase, receptor, type 2
Location	9q22.1
Position	chr9:84668551-85027070, 1
External Links	HGNC: 8032 Entrez Gene: 4915 Ensembl: ENSG00000148053 UCSC: uc004anz.1
No. of Studies	3 (Positive: 1; Negative: 1; trend: 1)
Overlap with SZ?	YES
Overlap with MDD?	YES

Gene related studies (count: 3)

Reference	Tested Markers	Statistical Values/Author Comments	Result Category	Comment on Study
Smith, E. N.,2009	SNP: rs2769605	For the AA sample, SNPs with the strongest statistical evidence for association included rs2111504 in DPY19L3 at 19q13.11 (P=1.5E-06) and rs2769605 in NTRK2 at 9q21.33 (P=4.5E-05).	Trend	Comment on Study
Soronen, P.,2011	SNP: rs3654	No significant association of this gene was observed in BD.	Negative	Comment on Study
Wang, Z., 2013	SNP: rs2769605, rs1565445, rs1387923	However, no significant association between NTRK2 gene polymorphisms and BP I susceptibility was observed after correcting for multiple comparisons. The results suggest that the NTRK2 gene polymorphism likely plays an essential role in treatment response to mood stabilizers in Han Chinese BP I patients.	Positive	Comment on Study

Gene functional annotation

Gene related GO terms (count: 63)

GO terms by PBA (count: 4)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0043235	receptor complex	cellular component	IDA[23382219]	20
GO:0045211	postsynaptic membrane	cellular component	IEA	68
GO:0006954	inflammatory response	biological process	IEA	23
GO:0005887	integral component of plasma membrane	cellular component	IDA[15494731]	158

GO terms by database search (count: 59)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0048011	neurotrophin TRK receptor signaling pathway	biological process	TAS	33
GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway	biological process	TAS	16
GO:0007631	feeding behavior	biological process	IEA	12
GO:0010008	endosome membrane	cellular component	IEA	17
GO:0048786	presynaptic active zone	cellular component	IEA	5
GO:2000811	negative regulation of anoikis	biological process	IEA	3
GO:0046928	regulation of neurotransmitter secretion	biological process	IEA	7
GO:0005524	ATP binding	molecular function	IEA	118
GO:0051968	positive regulation of synaptic transmission, glutamatergic	biological process	IEA	8
GO:0048935	peripheral nervous system neuron development	biological process	IEA	1
GO:0014068	positive regulation of phosphatidylinositol 3-kinase signaling	biological process	ISS	9
GO:0010976	positive regulation of neuron projection development	biological process	ISS	10
GO:0014047	glutamate secretion	biological process	IEA	6
GO:0060291	long-term synaptic potentiation	biological process	IEA	14
GO:0071356	cellular response to tumor necrosis factor	biological process	IEA	7
GO:0031547	brain-derived neurotrophic factor receptor signaling pathway	biological process	IMP[15494731]	1
GO:0030182	neuron differentiation	biological process	ISS	5
GO:0021987	cerebral cortex development	biological process	ISS	9
GO:0008284	positive regulation of cell proliferation	biological process	ISS	44
GO:0043121	neurotrophin binding	molecular function	IDA[11738045]; ISS	2
GO:0007568	aging	biological process	IEA	22
GO:0048403	brain-derived neurotrophic factor binding	molecular function	ISS	1
GO:0009416	response to light stimulus	biological process	IEA	5
GO:0018108	peptidyl-tyrosine phosphorylation	biological process	IEA	12
GO:0001570	vasculogenesis	biological process	IEA	4
GO:0046548	retinal rod cell development	biological process	IEA	2
GO:0007616	long-term memory	biological process	IEA	9
GO:0005791	rough endoplasmic reticulum	cellular component	IEA	4
GO:0007190	activation of adenylate cyclase activity	biological process	TAS	12
GO:0001764	neuron migration	biological process	ISS	18
GO:1990090	cellular response to nerve growth factor stimulus	biological process	IEA	4
GO:0043087	regulation of GTPase activity	biological process	ISS	5
GO:0050773	regulation of dendrite development	biological process	IEA	2
GO:0033138	positive regulation of peptidyl-serine phosphorylation	biological process	IEA	10
GO:0042803	protein homodimerization activity	molecular function	ISS	71
GO:0043195	terminal bouton	cellular component	IEA	17
GO:0010996	response to auditory stimulus	biological process	IEA	4
GO:0010628	positive regulation of gene expression	biological process	ISS	23
GO:0043204	perikaryon	cellular component	IEA	17
GO:0043524	negative regulation of neuron apoptotic process	biological process	ISS	26
GO:0021954	central nervous system neuron development	biological process	ISS	1
GO:0030426	growth cone	cellular component	IEA	22
GO:0048709	oligodendrocyte differentiation	biological process	IEA	5
GO:0060175	brain-derived neurotrophic factor-activated receptor activity	molecular function	IMP[15494731]	1
GO:0043197	dendritic spine	cellular component	IEA	21
GO:0050772	positive regulation of axonogenesis	biological process	ISS	4
GO:0042490	mechanoreceptor differentiation	biological process	IEA	3
GO:0009986	cell surface	cellular component	IEA	40
GO:0007612	learning	biological process	ISS	18
GO:0060076	excitatory synapse	cellular component	IEA	3
GO:0043410	positive regulation of MAPK cascade	biological process	ISS	13
GO:0007528	neuromuscular junction development	biological process	IEA	8
GO:0051896	regulation of protein kinase B signaling	biological process	IEA	1
GO:0046777	protein autophosphorylation	biological process	ISS	16
GO:0005829	cytosol	cellular component	IEA	223
GO:0035584	calcium-mediated signaling using intracellular calcium source	biological process	IEA	4
GO:0007623	circadian rhythm	biological process	IEA	40
GO:0097481	neuronal postsynaptic density	cellular component	IEA	6
GO:0046875	ephrin receptor binding	molecular function	IEA	5

Gene related KEGG pathways (count: 1)

KEGG pathways by PBA (count: 1)

ID	Name	No. of Genes in BDgene	Brief Description
hsa04010	MAPK signaling pathway	39

KEGG pathways by database search (count: 0)

Gene related BioCarta pathways (count: 0)

Gene related interactors from protein-protein interactions data in HPRD (count: 22)

Gene	Interactor	Interactor in BDgene?	Experiment Type	PMID
NTRK2	SH2B1	NO	in vitro	9856458
NTRK2	SQSTM1	NO	in vivo	12471037
NTRK2	NTF4	NO	in vivo	11855816
NTRK2	BDNF	YES	in vitro;in vivo	9312147
NTRK2	NCK1	NO	yeast 2-hybrid	12074588
NTRK2	SHC1	NO	in vitro;in vivo	12419535 , 16034442
NTRK2	SH2B2	NO	in vitro;in vivo	9856458
NTRK2	GIPC1	NO	in vitro;in vivo;yeast 2-hybrid	11251075 , 15304335 , 14617818
NTRK2	RASGRF1	NO	in vivo	15513915
NTRK2	NTF3	YES	in vivo	8621424
NTRK2	KIDINS220	NO	in vitro;in vivo	15167895
NTRK2	DOK5	YES	in vitro;yeast 2-hybrid	16647839
NTRK2	PTPN1	NO	in vitro	12237455
NTRK2	PTPN11	NO	in vitro	10386953
NTRK2	NGFR	NO	in vivo	9927421
NTRK2	UBB	NO	in vivo	16701206
NTRK2	DYNLL1	NO	in vivo	11157096
NTRK2	PLCG1	YES	in vitro;in vivo	12419535
NTRK2	TRAF6	NO	in vitro	18457658
NTRK2	SHC2	NO	in vivo	12006576 , 9507002
NTRK2	SHC3	NO	in vivo	9507002
NTRK2	FRS3	NO	in vitro	11432792

Related other genetic factors

Gene related SNPs (count: 49)

Literature-origin SNPs (count: 4)

rs_ID	Location	Functional Annotation	No. of Studies (Positive/Negative/Trend)
rs1565445	chr9:85002156 - 85002156(1)	intron_variant	1(0/1/0)
rs3654	chr9:84815576 - 84815576(1)	3_prime_UTR_variant; intron_variant	1(0/1/0)
rs2769605	chr9:85297756 - 85297756(1)		2(0/1/1)
rs1387923	chr9:85025721 - 85025721(1)	3_prime_UTR_variant; downstream_gene_variant	1(1/0/0)

LD-proxies (count: 45)

rs_ID	Location	Functional Annotation
rs7019128	chr9:84807319 - 84807319(1)	intron_variant
rs2013566	chr9:84811383 - 84811383(1)	3_prime_UTR_variant; intron_variant
rs12000011	chr9:84991960 - 84991960(1)	intron_variant
rs4636281	chr9:84996027 - 84996027(1)	intron_variant
rs3739804	chr9:84806716 - 84806716(1)	intron_variant
rs4388525	chr9:84999244 - 84999244(1)	intron_variant
rs4305979	chr9:84998960 - 84998960(1)	intron_variant
rs7019555	chr9:84999530 - 84999530(1)	intron_variant
rs4400465	chr9:84999247 - 84999247(1)	intron_variant
rs4242631	chr9:84996757 - 84996757(1)	intron_variant
rs4242630	chr9:84996630 - 84996630(1)	intron_variant
rs4877895	chr9:84998408 - 84998408(1)	intron_variant
rs4388524	chr9:84997284 - 84997284(1)	intron_variant
rs1565446	chr9:85002053 - 85002053(1)	intron_variant
rs1565447	chr9:85001992 - 85001992(1)	intron_variant
rs7036165	chr9:85003097 - 85003097(1)	intron_variant
rs7035804	chr9:85002821 - 85002821(1)	intron_variant
rs6559844	chr9:85000293 - 85000293(1)	intron_variant
rs4631550	chr9:84999898 - 84999898(1)	intron_variant
rs923559	chr9:85001617 - 85001617(1)	intron_variant
rs7023492	chr9:85000381 - 85000381(1)	intron_variant
rs4242632	chr9:85004296 - 85004296(1)	intron_variant
rs10125469	chr9:85005179 - 85005179(1)	intron_variant
rs4394478	chr9:85003470 - 85003470(1)	intron_variant
rs10125141	chr9:85007895 - 85007895(1)	intron_variant
rs4556163	chr9:85003611 - 85003611(1)	intron_variant
rs10115908	chr9:85008470 - 85008470(1)	intron_variant
rs7030960	chr9:85005505 - 85005505(1)	intron_variant
rs7857957	chr9:85006697 - 85006697(1)	intron_variant
rs7045296	chr9:85005325 - 85005325(1)	intron_variant
rs12553180	chr9:85005413 - 85005413(1)	intron_variant
rs1490405	chr9:85007470 - 85007470(1)	intron_variant
rs1490404	chr9:85007615 - 85007615(1)	intron_variant
rs1490407	chr9:85007409 - 85007409(1)	intron_variant
rs1490406	chr9:85007424 - 85007424(1)	intron_variant
rs4142910	chr9:85010182 - 85010182(1)	intron_variant
rs1948308	chr9:85001342 - 85001342(1)	intron_variant
rs7853433	chr9:85012816 - 85012816(1)	intron_variant
rs7036090	chr9:85002774 - 85002774(1)	intron_variant
rs10116750	chr9:85009408 - 85009408(1)	intron_variant
rs2378676	chr9:85004508 - 85004508(1)	intron_variant
rs10123600	chr9:85009718 - 85009718(1)	intron_variant
rs1490403	chr9:85023591 - 85023591(1)	3_prime_UTR_variant; downstream_gene_variant
rs729560	chr9:85019390 - 85019390(1)	intron_variant
rs1387925	chr9:85018073 - 85018073(1)	intron_variant

Gene related CNVs (count: 0)

Gene related other variants (count: 0)

Gene related regions (count: 4)

Region Name	Position	No. of Studies (Positive/Negative/Trend)
9q21-32	chr9:65000000-114900000	1 (0/1/0)
Chr 9	chr9:0-138394717	3 (0/3/0)
9q21-22	chr9:65000000-99800000	1 (0/1/0)
9q21	chr9:65000000-87800000	3 (1/1/1)

Overlap with schizophrenia (SZ) and major depressive disorder (MDD)

Gene relationship with SZ

Overlap with SZ from cross-disorder studies (count: 0)

Overlap with SZ from candidate gene intersection analysis (count: 1)

Reference	ID in SZGene	Result Category
17720314	542	Negative

Gene relationship with MDD

Overlap with MDD from cross-disorder studies (count: 1)

Reference	Description	Category in MDD
21438144	No significant association of this gene was observed in MDD.	Negative

Overlap with MDD from candidate gene intersection analysis (count: 4)

Reference	Description	Category in MDD	Link in MK4MDD
19844206	The most significant association was found between NTRK2 haplotype CAG (rs2289658, rs2289657 and rs2289656) and relative reduction of HAM-D21 score with a nominal P = 0.0002 and an effect size of squared R = 0.20	Pos	NTRK2
15303102	Genes altered in major depressive disorder	Pos	NTRK2
17353912	Selected differentially expressed genes in hippocampus	Pos	NTRK2
20386568	The expression of this gene was altered in the locus coeruleus of MDD	Pos	NTRK2

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Region: chr9:84668551..85027070 View in gBrowse