Gene Report

Basic Information

Approved Symbol	HTR2A
Approved Name	5-hydroxytryptamine (serotonin) receptor 2A, G protein-coupled
Previous Symbol	HTR2
Previous Name	5-hydroxytryptamine (serotonin) receptor 2A
Symbol Alias	5-HT2A
Location	13q14-q21
Position	chr13:47405677-47471211 (-)
External Links	Entrez Gene: 3356 Ensembl: ENSG00000102468 UCSC: uc010acr.3 HGNC ID: 5293
No. of Studies (Positive/Negative)	9(7/2)
Type	Literature-origin; SNP mapped; Protein mapped

Positive relationships between HTR2A and MDD (count: 5)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
5-HT2A	Du, 2000	patients and normal controls	P-value=0.03	The major finding of this study was a significant associatio...... The major finding of this study was a significant association between the 102 C allele in 5-HT2A receptor gene and major depression, chi(2) = 4.5, df = 1, P = 0.03, particularly in patients with suicidal ideation, chi(2) = 8.5, df = 1, P < 0.005. More...
5-HT(2A)	Arias B, 2001	Patients and nomal controls	OR = 5.50; 95% CI = 1.18-35.20; P = 0.01	Significant differences in allele (chi-square = 4.13, df = 1...... Significant differences in allele (chi-square = 4.13, df = 1, P = 0.04) and genotype (chi-square = 6.19, df = 2, P = 0.04) distributions were found between non-suicide attempters and suicide attempters. Moreover, those patients carrying 5-HT(2A)-C allele had more than five times the risk for attempting suicide than noncarriers (OR = 5.50, 95% CI = 1.18-35.20, P = 0.01). More...
5-HTR2A	Choi, 2004	patients and normal controls	genotype: chi(2) = 10.78, d.f. = 2, P-value = 0.005; allele:chi(2) = 10.18, P-value = 0.001; OR = 2.46, 95% CI 1.40-4.32	This polymorphism was analyzed in 189 patients with MDD and ...... This polymorphism was analyzed in 189 patients with MDD and in 148 unrelated healthy controls using a case-control design, which revealed a significant difference in the genotype distributions (chi(2) = 10.78, d.f. = 2, p = 0.005). The frequency of the -1438G allele was also much higher in MDD patients than in normal controls (chi(2) = 7.20, p = 0.007; OR = 1.52, 95% CI 1.12-2.06). We also found significantly more carriers of the G allele (GG+AG genotypes) in MDD patients than in normal controls (chi(2) = 10.18, p = 0.001; OR = 2.46, 95% CI 1.40-4.32). More...
HTR2A	Klempan, 2009	patients and normal controls		Selected differentially expressed genes in BA44 to BA47 (ANO...... Selected differentially expressed genes in BA44 to BA47 (ANOVA and t-test P < 0.01, fold change 1.3t) More...
HTR2A	Belzeaux, 2010	patients and normal controls		We also observed that variations in other mRNA expression we...... We also observed that variations in other mRNA expression were associated with treatment efficacy or clinical improvement (CREB1, HDAC5, HSPA2, HTR1B, HTR2A, and SLC6A4/5HTT). More...

Positive relationships between HTR2A and other components at different levels (count: 4)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description
Name in Literature	Related Components
HTR2A		GNB3(GNB3)	gene	Lin, 2009	patients only	P-value=0.025	The generalized multifactor dimensionality reduction approac...... The generalized multifactor dimensionality reduction approach identified a significant gene-gene interaction (P-value=0.025) involving GNB3 and HTR2A More...
HTR2A		Sodium-dependent serotonin transporter(serotonin transporter (5-HTT))	protein	Laje, 2010	patients and normal controls		Genetic variation in HTR2A that was previously associated wi...... Genetic variation in HTR2A that was previously associated with citalopram treatment outcome was also associated with thalamic 5-HTT binding. More...
HTR2A		Thalamus(thalamus)	brain morphology and function	Laje, 2010	patients and normal controls		Genetic variation in HTR2A that was previously associated wi...... Genetic variation in HTR2A that was previously associated with citalopram treatment outcome was also associated with thalamic 5-HTT binding. More...
5-HT2A		Suicide(suicide attempt)	symptoms	Du, 2000	patients and normal controls	P-value<0.05	The major finding of this study was a significant associatio...... The major finding of this study was a significant association between the 102 C allele in 5-HT2A receptor gene and major depression, chi(2) = 4.5, df = 1, P = 0.03, particularly in patients with suicidal ideation, chi(2) = 8.5, df = 1, P < 0.005. Furthermore, we found that patients with a 102 C/C genotype had a significantly higher mean HAMD item 3 score (indication of suicidal ideation) than T/C or T/T genotype patients. More...

Positive relationship network of HTR2A in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between HTR2A and MDD (count: 2)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
5HTR2A	Yoon HK, 2008	Patients and nomal controls		There were no significant differences in the genotype distri...... There were no significant differences in the genotype distributions or allelic frequencies in the two serotonergic polymorphisms between suicide attempters and normal controls. None of the two serotonergic polymorphisms was correlated with lethality. More...
HTR2A	Kishi T, 2009	Patients and nomal controls		We did not detect significant an association of HTR2A with M...... We did not detect significant an association of HTR2A with MDD and BP in allele/genotype-wise or haplotype-wise analysis More...

Negative relationships between HTR2A and other components at different levels (count: 0)

HTR2A related SNPs in MK4MDD (count: 3)

#rs	Location	Annotation	No. of Studies (Positive/Negative)
rs6313	chr13:47469940(Forward)	intron_variant; synonymous_variant	1(1/0)
rs6311	chr13:47471478(Forward)	upstream_gene_variant	2(1/1)
rs7333412	chr13:47403360(Forward)	downstream_gene_variant	1(1/0)

HTR2A related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
5-hydroxytryptamine receptor 2A	P28223	8(7/1)	Literature-origin

HTR2A related GO terms (count: 32)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0007268	synaptic transmission	biological process	TAS[9109547]
GO:0006950	response to stress	biological process	IEA

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0008284	positive regulation of cell proliferation	biological process	IEA
GO:0043267	negative regulation of potassium ion transport	biological process	IEA
GO:0014059	regulation of dopamine secretion	biological process	IEA
GO:0043198	dendritic shaft	cellular component	IEA
GO:0005886	plasma membrane	cellular component	IDA[15862800]; TAS
GO:0007613	memory	biological process	IEA
GO:0019233	sensory perception of pain	biological process	IEA
GO:0008144	drug binding	molecular function	IDA[15831837]
GO:0001965	G-protein alpha-subunit binding	molecular function	IEA
GO:0005829	cytosol	cellular component	IEA
GO:0006661	phosphatidylinositol biosynthetic process	biological process	IMP[19057895]
GO:0004993	serotonin receptor activity	molecular function	IDA[7582481]
GO:0001659	temperature homeostasis	biological process	IEA
GO:0004435	phosphatidylinositol phospholipase C activity	molecular function	IMP[16517693]
GO:0051378	serotonin binding	molecular function	IDA[7582481]
GO:0005887	integral to plasma membrane	cellular component	TAS[9109547]
GO:0014065	phosphatidylinositol 3-kinase cascade	biological process	IMP[16517693]
GO:0007210	serotonin receptor signaling pathway	biological process	IMP[18703043]
GO:0070371	ERK1 and ERK2 cascade	biological process	IMP[19057895]
GO:0008219	cell death	biological process	IEA
GO:0032403	protein complex binding	molecular function	IEA
GO:0043406	positive regulation of MAP kinase activity	biological process	IEA
GO:0042493	response to drug	biological process	IDA[15862800]
GO:0071886	1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding	molecular function	IDA[19057895]
GO:0045907	positive regulation of vasoconstriction	biological process	IEA
GO:0051209	release of sequestered calcium ion into cytosol	biological process	IDA[15862800]; IMP[18703043]
GO:0007568	aging	biological process	IEA
GO:0007208	phospholipase C-activating serotonin receptor signaling pathway	biological process	IEA
GO:0051967	negative regulation of synaptic transmission, glutamatergic	biological process	IEA
GO:0030431	sleep	biological process	IEA

HTR2A related KEGG pathways (count: 3)

ID	Name	Brief Description	Full Description
Literature-origin KEGG pathway
hsa04020	calcium signaling_pathway	Calcium signaling pathway	Ca2+ that enters the cell from the outside is a principal so...... Ca2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this external source of signal Ca2+ by activating various entry channels with widely different properties. The voltage-operated channels (VOCs) are found in excitable cells and generate the rapid Ca2+ fluxes that control fast cellular processes. There are many other Ca2+-entry channels, such as the receptor-operated channels (ROCs), for example the NMDA (N-methyl-D-aspartate) receptors (NMDARs) that respond to glutamate. There also are second-messenger-operated channels (SMOCs) and store-operated channels (SOCs). The other principal source of Ca2+ for signalling is the internal stores that are located primarily in the endoplasmic/sarcoplasmic reticulum (ER/SR), in which inositol-1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RYRs) regulate the release of Ca2+. The principal activator of these channels is Ca2+ itself and this process of Ca2+-induced Ca2+ release is central to the mechanism of Ca2+ signalling. Various second messengers or modulators also control the release of Ca2+. IP3, which is generated by pathways using different isoforms of phospholipase C (PLCbeta, delta, epsilon, gamma and zeta), regulates the IP3Rs. Cyclic ADP-ribose (cADPR) releases Ca2+ via RYRs. Nicotinic acid adenine dinucleotide phosphate (NAADP) may activate a distinct Ca2+ release mechanism on separate acidic Ca2+ stores. Ca2+ release via the NAADP-sensitive mechanism may also feedback onto either RYRs or IP3Rs. cADPR and NAADP are generated by CD38. This enzyme might be sensitive to the cellular metabolism, as ATP and NADH inhibit it. The influx of Ca2+ from the environment or release from internal stores causes a very rapid and dramatic increase in cytoplasmic calcium concentration, which has been widely exploited for signal transduction. Some proteins, such as troponin C (TnC) involved in muscle contraction, directly bind to and sense Ca2+. However, in other cases Ca2+ is sensed through intermediate calcium sensors such as calmodulin (CALM). More...

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04080	neuroactive ligand_receptor_interaction	Neuroactive ligand-receptor interaction
hsa04540	gap junction	Gap junction	Gap junctions contain intercellular channels that allow dire...... Gap junctions contain intercellular channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is formed by docking of two 'hemichannels', each containing six connexins, contributed by each neighboring cell. These channels permit the direct transfer of small molecules including ions, amino acids, nucleotides, second messengers and other metabolites between adjacent cells. Gap junctional communication is essential for many physiological events, including embryonic development, electrical coupling, metabolic transport, apoptosis, and tissue homeostasis. Communication through Gap Junction is sensitive to a variety of stimuli, including changes in the level of intracellular Ca2+, pH, transjunctional applied voltage and phosphorylation/dephosphorylation processes. This figure represents the possible activation routes of different protein kinases involved in Cx43 and Cx36 phosphorylation. More...

HTR2A related BioCarta pathways (count: 0)

HTR2A related Reactome pathways (count: 6)

ID	Name	Description
Gene mapped Reactome pathways
REACT_18283	g alpha_q_signalling_events	The classic signalling route for G alpha (q) is activation o...... The classic signalling route for G alpha (q) is activation of phospholipase C beta thereby triggering phosphoinositide hydrolysis, calcium mobilization and protein kinase C activation. This provides a path to calcium-regulated kinases and phosphatases, GEFs, MAP kinase cassettes and other proteins that mediate cellular responses ranging from granule secretion, integrin activation, and aggregation in platelets. Gq participates in many other signalling events including direct interaction with RhoGEFs that stimulate RhoA activity and inhibition of PI3K. Both in vitro and in vivo, the G-protein Gq seems to be the predominant mediator of the activation of platelets. More...
REACT_14828	class a1_rhodopsin_like_receptors	Rhodopsin-like receptors. They represent members which inclu...... Rhodopsin-like receptors. They represent members which include hormone, light and neurotransmitter receptors and encompass a wide range of functions including many autocrine, paracrine and endocrine processes. More...
REACT_16983	amine ligand_binding_receptors	The class A (rhodopsin-like) GPCRs that bind to classical bi...... The class A (rhodopsin-like) GPCRs that bind to classical biogenic amine ligands are annotated here. The amines involved (acetylcholine, adrenaline, noradrenaline, dopamine, serotonin and histamine) can all act as neurotransmitters in humans. The so-called 'trace amines', used when referring to p-tyramine, beta-phenylethylamine, tryptamine and octopamine, can also bind to recently-discovered GPCRs. More...
REACT_19184	downstream events_in_gpcr_signaling	G protein-coupled receptors. The beta:gamma G-protein dimer ...... G protein-coupled receptors. The beta:gamma G-protein dimer is also involved in downstream signaling , and some receptors form part of metastable complexes of receptor and accessory proteins such as the arrestins. GPCRs are involved in many diverse signaling events , using a variety of pathways that include modulation of adenylyl cyclase, phospholipase C, the mitogen activated protein kinases (MAPKs), extracellular signal regulated kinase (ERK) c-Jun-NH2-terminal kinase (JNK) and p38 MAPK. More...
REACT_21340	gpcr ligand_binding	There are more than 800 G-protein coupled receptor. GPCRs ar...... There are more than 800 G-protein coupled receptor. GPCRs are receptors for a diverse range of ligands from large proteins to photons and have an equal diverstiy of ligand-binding mechanisms. Classical GPCR signaling involves signal transduction via heterotrimeric G-proteins, however many G-protein independent mechanisms have been reported. More...
REACT_17064	serotonin receptors	Serotonin. Serotonin.

HTR2A related interactors from protein-protein interaction data in HPRD (count: 16)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
HTR2A	RPS6KA3	No	in vitro;in vivo;yeast 2-hybrid	16537434
HTR2A	EIF3F	No	yeast 2-hybrid	16537434
HTR2A	JAK2	No	in vivo	9169451
HTR2A	GNAQ	No	in vivo	11916537
HTR2A	PON2	No	yeast 2-hybrid	16537434
HTR2A	GLUL	Yes	yeast 2-hybrid	16537434
HTR2A	GNA11	No	in vivo	11916537
HTR2A	MRPL28	No	yeast 2-hybrid	16537434
HTR2A	DLG4	Yes	in vitro;in vivo	12682061
HTR2A	PPP5C	No	yeast 2-hybrid	16537434
HTR2A	NME3	No	yeast 2-hybrid	16537434
HTR2A	NTRK3	Yes	yeast 2-hybrid	16537434
HTR2A	GNAI1	No	in vivo	11916537
HTR2A	ANKS1B	No	yeast 2-hybrid	16537434
HTR2A	MAP1A	Yes	yeast 2-hybrid	16537434
HTR2A	NDUFB10	No	yeast 2-hybrid	16537434

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Literature-origin KEGG pathway

Gene mapped KEGG pathways

Gene mapped Reactome pathways