ADHDgene Database

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Large-scale studies

Data Summary

Published Variant
- SNP: 1391
- CNV: 398
- Others: 173
Published Gene: 359
Published Region: 128
Pathway by PBA: 8
Study: 361

Detail ...

Gene Report

Basic Info

Approved Symbol	ADRA2A
Previous Symbol	ADRA2, ADRA2R
Symbol Alias	ADRAR
Approved Name	adrenergic, alpha-2A-, receptor
Name Alias	alpha-2AAR subtype C10, " alpha-2A-adrenergic receptor"
Location	10q24-q26
Position	chr10:112836790-112840665, +
External Links	HGNC: 281 Entrez Gene: 150 Ensembl: ENSG00000150594 UCSC: uc001kzo.2
No. of Studies	12 (significant: 4; non-significant: 8; trend: 0)
Source	Literature-origin; Mapped by LD-proxy; Mapped by literature SNP

Gene related studies (count: 12)

Reference	Statistical Values/Author Comments	Result of Statistical Analysis
Gizer IR, 2009	The present study does not support a relation between ADHD and this gene.	Non-significant
Cho SC, 2008(b)	C allele of ADRA2A DraI polymorphism showed preferential transmission; haplotype C/C P-value=0.051, X²=3.80; a trend of over-transmission of haplotype C/C was observed	Significant
Hawi, Z., 2012	This gene did not show significant association with ADHD.	Non-significant
de Cerqueira CC, 2011	chi-square test P-value=0.080, X²=5.044 for three-marker haplotype frequencies, which showed no significant differences between patients and controls	Non-significant
Xu C, 2001	no evidence for linkage of the ADRA2A gene with ADHD was found using the transmission disequilibrium test in this set of families	Non-significant
Roman T, 2003	there was no evidence of association between the ADRA2A MspI variant and the disorder, but effects of the ADRA2A gene on inattention and combined symptom scores were detected	Non-significant
Park L, 2005	haplotype 212 (rarer alleles of the DraI and MspI RFLPs, and the common allele of the HhaI RFLP) TDT P-value=0.013, X²=6.23, RR=5.50 in ADHD-C; TDT P-value=0.011, X²=6.55, RR=3.40 in ADHD-(C+PI); supported the hypothesis that an allele of the ADRA2A gene is associated and linked with the ADHD combined subtype	Significant
Bobb AJ, 2005	no polymorphism was associated with ADHD	Non-significant
Wang B, 2006	haplotype M (C allele)/C of MspI/DraI, P-value=0.072, X² (1df)=3.233 with the ADHD-C subtype; weak evidence for a possible role of ADRA2A	Non-significant
Schmitz M, 2006	CC+CG genotypes, P-value=0.02, OR=3.78, ADRA2A may be associated with ADHD inattentive type	Significant
Brookes K, 2006	UNPHASED TDT P-value=0.141, global P-value=0.505, WHAP TDT P_sum P-value=0.88, no SNP with nominal P-value<0.05 located in this gene	Non-significant
Deupree JD, 2006	HhaI-DraI haplotype 1 1 (GC), TDT P-value=0.035, sigma² (1df) =4.45; MspI-HhaI-DraI haplotype 1 1 1 or CGC, TDT P-value=0.046, sigma² (1df) =4.00; ADRA2A may play a role in ADHD	Significant

Gene related SNPs (count: 8)

Literature-origin SNPs (count: 7)

rs_ID	Location	Functional Annotation	No. of Studies (significant/non-significant/trend)
rs180045	Chr5:178639086(Fwd)	intron_variant	1(0/1/0)
rs553668	Chr10:112839579(Fwd)	3_prime_UTR_variant	3(1/2/0)
rs521674	Chr10:112835590(Fwd)	upstream_gene_variant	1(0/1/0)
rs583668	Chr16:33967254(Fwd); Chr2:133009053(Rev); ChrY:10039596(Fwd)	downstream_gene_variant(ENST00000515896;ENST00000365304;ENST00000363564) \| intron_variant(ENST00000470729) \| nc_transcript_variant(ENST00000470729) \| upstream_gene_variant(ENST00000445125;ENST00000539813)	3(2/1/0)
rs1800544	Chr10:112836503(Fwd)	upstream_gene_variant	11(1/10/0)
rs1800545	Chr10:112837538(Fwd)	5_prime_UTR_variant	3(1/2/0)
rs602618	Chr10:112843085(Fwd)	downstream_gene_variant	1(0/1/0)

LD-proxies (count: 1)

rs_ID	Location	Functional Annotation
rs638019	Chr10:112831829(Fwd)	upstream_gene_variant

Gene related CNVs (count: 0)

Gene related other variant (count: 0)

Gene related regions (count: 0)

Gene related GO terms (count: 63)

GO terms by PBA (with statistical significance of FDR<0.05) (count: 0)

GO terms by database search (count: 63)

ID	Name	Type	Evidence[PMID]	No. of Genes in ADHDgene
GO:0007596	blood coagulation	Biological Process		83
GO:0007565	female pregnancy	Biological Process		14
GO:0010700	negative regulation of norepinephrine secretion	Biological Process	NAS[16531006]; TAS[19477270]	4
GO:0008284	positive regulation of cell proliferation	Biological Process	TAS[10896916]	69
GO:0007194	negative regulation of adenylate cyclase activity	Biological Process	ISS[1354394]	10
GO:0007186	G-protein coupled receptor signaling pathway	Biological Process	ISS[19965390]	72
GO:0007266	Rho protein signal transduction	Biological Process	TAS[9624180]	11
GO:0007265	Ras protein signal transduction	Biological Process	TAS[8226727]	15
GO:0030818	negative regulation of cAMP biosynthetic process	Biological Process	IDA[16531006]	7
GO:0030335	positive regulation of cell migration	Biological Process	IMP[17655843]	29
GO:0031696	alpha-2C adrenergic receptor binding	Molecular Function	IPI[16605244]	1
GO:0031692	alpha-1B adrenergic receptor binding	Molecular Function		2
GO:0019901	protein kinase binding	Molecular Function	IPI[15653687]	51
GO:0016323	basolateral plasma membrane	Cellular Component	TAS[17655843]	29
GO:0030168	platelet activation	Biological Process		38
GO:0030036	actin cytoskeleton organization	Biological Process	TAS[9624180]	21
GO:0001819	positive regulation of cytokine production	Biological Process	IDA[17655843]	3
GO:0002526	acute inflammatory response	Biological Process		3
GO:0004938	alpha2-adrenergic receptor activity	Molecular Function	IDA[10948191]; ISS[1354394]	3
GO:0006112	energy reserve metabolic process	Biological Process		25
GO:0006260	DNA replication	Biological Process		27
GO:0006928	cellular component movement	Biological Process	TAS[9624180]	16
GO:0007165	signal transduction	Biological Process	TAS[2823383]	171
GO:0005515	protein binding	Molecular Function	IPI[16531006]	910
GO:0005737	cytoplasm	Cellular Component	IDA[19477270]	690
GO:0005886	plasma membrane	Cellular Component		772
GO:0005887	integral to plasma membrane	Cellular Component	IDA[10948191]	220
GO:0071882	phospholipase C-activating adrenergic receptor signaling pathway	Biological Process	IDA[10948191]	1
GO:0071883	activation of MAPK activity by adrenergic receptor signaling pathway	Biological Process	IDA[10948191]	3
GO:0090303	positive regulation of wound healing	Biological Process	IMP[17655843]	1
GO:1901020	negative regulation of calcium ion transmembrane transporter activity	Biological Process	ISS[1354394]	3
GO:0046982	protein heterodimerization activity	Molecular Function	IPI[16605244]	68
GO:0046676	negative regulation of insulin secretion	Biological Process	IMP[10952463]	3
GO:0045955	negative regulation of calcium ion-dependent exocytosis	Biological Process	IC[19965390]	2
GO:0045909	positive regulation of vasodilation	Biological Process		5
GO:0050995	negative regulation of lipid catabolic process	Biological Process	IGI[10948198]	5
GO:0050955	thermoception	Biological Process		2
GO:0050892	intestinal absorption	Biological Process	TAS[17655843]	3
GO:0050796	regulation of insulin secretion	Biological Process		22
GO:0051926	negative regulation of calcium ion transport	Biological Process		4
GO:0051380	norepinephrine binding	Molecular Function	IDA[2823383]	4
GO:0051379	epinephrine binding	Molecular Function	IDA[10948191]	5
GO:0051044	positive regulation of membrane protein ectodomain proteolysis	Biological Process	IDA[17655843]	3
GO:0071881	adenylate cyclase-inhibiting adrenergic receptor signaling pathway	Biological Process	IDA[10948191]	1
GO:0071878	negative regulation of adrenergic receptor signaling pathway	Biological Process		1
GO:0070473	negative regulation of uterine smooth muscle contraction	Biological Process		2
GO:0061179	negative regulation of insulin secretion involved in cellular response to glucose stimulus	Biological Process	IMP[19965390]	1
GO:0032148	activation of protein kinase B activity	Biological Process	IDA[17215105]	6
GO:0032795	heterotrimeric G-protein binding	Molecular Function	IDA[10948191]	1
GO:0031996	thioesterase binding	Molecular Function	IPI[19477270]	3
GO:0032147	activation of protein kinase activity	Biological Process	IDA[15653687]	5
GO:0035625	epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway	Biological Process	IDA[17215105]	4
GO:0042593	glucose homeostasis	Biological Process	IMP[10952463]	18
GO:0032811	negative regulation of epinephrine secretion	Biological Process	NAS[16531006]	3
GO:0032870	cellular response to hormone stimulus	Biological Process	IGI[10948198]	7
GO:0043235	receptor complex	Cellular Component	IDA[10948191]	11
GO:0043268	positive regulation of potassium ion transport	Biological Process	ISS[1354394]	3
GO:0042596	fear response	Biological Process		5
GO:0042803	protein homodimerization activity	Molecular Function	IDA[16605244]	113
GO:0045202	synapse	Cellular Component		31
GO:0045741	positive regulation of epidermal growth factor-activated receptor activity	Biological Process	IDA[17655843]	3
GO:0043406	positive regulation of MAP kinase activity	Biological Process	IDA[19477270]	10
GO:0044281	small molecule metabolic process	Biological Process		248

Gene related KEGG pathways (count: 1)

ID	Name	No. of Genes in ADHDgene	Brief Description
hsa04080	Neuroactive ligand-receptor interaction	93

Genes shared at least 5 GO terms with ADRA2A (count: 82)

Gene Symbol	Pathway Count	Pathway List
ADRA2C	21	blood coagulation; female pregnancy; negative regulation of norepinephrine secretion; G-protein coupled receptor signaling pathway; platelet activation; alpha2-adrenergic receptor activity; energy reserve metabolic process; protein binding; cytoplasm; plasma membrane; integral to plasma membrane; activation of MAPK activity by adrenergic receptor signaling pathway; protein heterodimerization activity; regulation of insulin secretion; epinephrine binding; negative regulation of uterine smooth muscle contraction; activation of protein kinase B activity; epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway; negative regulation of epinephrine secretion; protein homodimerization activity; small molecule metabolic process;
ADRA2B	14	blood coagulation; female pregnancy; negative regulation of norepinephrine secretion; G-protein coupled receptor signaling pathway; platelet activation; alpha2-adrenergic receptor activity; protein binding; plasma membrane; integral to plasma membrane; activation of MAPK activity by adrenergic receptor signaling pathway; epinephrine binding; activation of protein kinase B activity; epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway; negative regulation of epinephrine secretion;
INS	11	positive regulation of cell proliferation; G-protein coupled receptor signaling pathway; positive regulation of cell migration; energy reserve metabolic process; protein binding; positive regulation of vasodilation; negative regulation of lipid catabolic process; regulation of insulin secretion; activation of protein kinase B activity; glucose homeostasis; small molecule metabolic process;
VEGFA	10	blood coagulation; positive regulation of cell proliferation; positive regulation of cell migration; platelet activation; protein binding; cytoplasm; protein heterodimerization activity; activation of protein kinase activity; protein homodimerization activity; positive regulation of MAP kinase activity;
ADRB1	9	Rho protein signal transduction; protein binding; cytoplasm; plasma membrane; integral to plasma membrane; protein heterodimerization activity; norepinephrine binding; epinephrine binding; fear response;
BCAR1	8	blood coagulation; G-protein coupled receptor signaling pathway; positive regulation of cell migration; protein kinase binding; platelet activation; protein binding; cytoplasm; plasma membrane;
MAPK1	8	blood coagulation; positive regulation of cell proliferation; Ras protein signal transduction; positive regulation of cell migration; platelet activation; signal transduction; protein binding; cytoplasm;
PIK3CG	8	blood coagulation; G-protein coupled receptor signaling pathway; platelet activation; protein binding; cytoplasm; plasma membrane; positive regulation of MAP kinase activity; small molecule metabolic process;
ADAM17	8	positive regulation of cell proliferation; positive regulation of cell migration; protein binding; cytoplasm; plasma membrane; integral to plasma membrane; epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway; positive regulation of epidermal growth factor-activated receptor activity;
CHRM3	8	G-protein coupled receptor signaling pathway; basolateral plasma membrane; energy reserve metabolic process; signal transduction; plasma membrane; integral to plasma membrane; regulation of insulin secretion; small molecule metabolic process;
ADRB3	8	energy reserve metabolic process; protein binding; plasma membrane; integral to plasma membrane; norepinephrine binding; epinephrine binding; receptor complex; protein homodimerization activity;
ARRB2	7	blood coagulation; alpha-1B adrenergic receptor binding; basolateral plasma membrane; platelet activation; protein binding; cytoplasm; plasma membrane;
ITPR1	7	blood coagulation; platelet activation; energy reserve metabolic process; signal transduction; protein binding; regulation of insulin secretion; small molecule metabolic process;
ITPR2	7	blood coagulation; platelet activation; energy reserve metabolic process; signal transduction; plasma membrane; regulation of insulin secretion; small molecule metabolic process;
PRKAR2B	7	blood coagulation; energy reserve metabolic process; signal transduction; cytoplasm; plasma membrane; regulation of insulin secretion; small molecule metabolic process;
STXBP3	7	blood coagulation; basolateral plasma membrane; platelet activation; protein binding; cytoplasm; plasma membrane; negative regulation of calcium ion-dependent exocytosis;
EDNRA	7	positive regulation of cell proliferation; G-protein coupled receptor signaling pathway; Rho protein signal transduction; negative regulation of cAMP biosynthetic process; signal transduction; plasma membrane; integral to plasma membrane;
ILK	7	positive regulation of cell proliferation; positive regulation of cell migration; protein kinase binding; protein binding; cytoplasm; plasma membrane; positive regulation of MAP kinase activity;
CORO1A	7	positive regulation of cell migration; actin cytoskeleton organization; cellular component movement; protein binding; cytoplasm; plasma membrane; protein homodimerization activity;
GHR	7	protein kinase binding; protein binding; plasma membrane; integral to plasma membrane; cellular response to hormone stimulus; receptor complex; protein homodimerization activity;
ERBB2	7	basolateral plasma membrane; signal transduction; protein binding; plasma membrane; protein heterodimerization activity; receptor complex; positive regulation of MAP kinase activity;
CACNA1C	7	energy reserve metabolic process; protein binding; cytoplasm; plasma membrane; regulation of insulin secretion; glucose homeostasis; small molecule metabolic process;
SNAP25	7	energy reserve metabolic process; protein binding; cytoplasm; plasma membrane; regulation of insulin secretion; synapse; small molecule metabolic process;
APOA1	6	blood coagulation; G-protein coupled receptor signaling pathway; platelet activation; protein binding; plasma membrane; small molecule metabolic process;
CFL1	6	blood coagulation; Rho protein signal transduction; platelet activation; actin cytoskeleton organization; protein binding; cytoplasm;
MGLL	6	blood coagulation; platelet activation; plasma membrane; protein homodimerization activity; synapse; small molecule metabolic process;
PDE2A	6	blood coagulation; negative regulation of cAMP biosynthetic process; protein binding; cytoplasm; plasma membrane; protein homodimerization activity;
PIK3R1	6	blood coagulation; positive regulation of cell migration; platelet activation; protein binding; plasma membrane; small molecule metabolic process;
PRKCB	6	blood coagulation; platelet activation; signal transduction; protein binding; cytoplasm; plasma membrane;
PRKG1	6	blood coagulation; actin cytoskeleton organization; signal transduction; protein binding; cytoplasm; plasma membrane;
RASGRP2	6	blood coagulation; Ras protein signal transduction; platelet activation; signal transduction; plasma membrane; synapse;
DRD3	6	positive regulation of cell proliferation; negative regulation of adenylate cyclase activity; G-protein coupled receptor signaling pathway; protein binding; plasma membrane; integral to plasma membrane;
DRD2	6	negative regulation of adenylate cyclase activity; protein binding; plasma membrane; integral to plasma membrane; negative regulation of insulin secretion; activation of protein kinase activity;
DRD4	6	negative regulation of adenylate cyclase activity; negative regulation of cAMP biosynthetic process; protein binding; plasma membrane; integral to plasma membrane; fear response;
ADCY4	6	energy reserve metabolic process; signal transduction; protein binding; cytoplasm; plasma membrane; small molecule metabolic process;
CACNA1A	6	energy reserve metabolic process; protein binding; cytoplasm; plasma membrane; regulation of insulin secretion; small molecule metabolic process;
STX1A	6	energy reserve metabolic process; protein binding; plasma membrane; protein heterodimerization activity; regulation of insulin secretion; small molecule metabolic process;
VAMP2	6	energy reserve metabolic process; protein binding; plasma membrane; integral to plasma membrane; regulation of insulin secretion; small molecule metabolic process;
ACHE	6	DNA replication; protein binding; plasma membrane; protein homodimerization activity; synapse; small molecule metabolic process;
PRKD1	6	signal transduction; protein binding; cytoplasm; plasma membrane; integral to plasma membrane; small molecule metabolic process;
ADRB2	6	protein binding; plasma membrane; integral to plasma membrane; norepinephrine binding; receptor complex; protein homodimerization activity;
FZD4	6	protein binding; cytoplasm; plasma membrane; integral to plasma membrane; protein heterodimerization activity; protein homodimerization activity;
ADORA2A	5	blood coagulation; protein binding; plasma membrane; integral to plasma membrane; protein heterodimerization activity;
ARRB1	5	blood coagulation; platelet activation; protein binding; cytoplasm; plasma membrane;
F2RL2	5	blood coagulation; platelet activation; protein binding; plasma membrane; integral to plasma membrane;
GP1BB	5	blood coagulation; platelet activation; protein binding; plasma membrane; integral to plasma membrane;
JAM3	5	blood coagulation; protein binding; plasma membrane; protein heterodimerization activity; protein homodimerization activity;
PTPRJ	5	blood coagulation; protein kinase binding; protein binding; plasma membrane; integral to plasma membrane;
STX4	5	blood coagulation; basolateral plasma membrane; platelet activation; protein binding; plasma membrane;
SYK	5	blood coagulation; protein kinase binding; platelet activation; protein binding; plasma membrane;
TRPC3	5	blood coagulation; platelet activation; protein binding; plasma membrane; integral to plasma membrane;
VEGFB	5	blood coagulation; platelet activation; protein binding; protein heterodimerization activity; protein homodimerization activity;
AQP4	5	female pregnancy; basolateral plasma membrane; cytoplasm; plasma membrane; integral to plasma membrane;
CAV3	5	positive regulation of cell proliferation; protein binding; plasma membrane; negative regulation of calcium ion transport; glucose homeostasis;
CHRM1	5	positive regulation of cell proliferation; G-protein coupled receptor signaling pathway; signal transduction; plasma membrane; integral to plasma membrane;
EREG	5	positive regulation of cell proliferation; positive regulation of cytokine production; protein binding; integral to plasma membrane; positive regulation of epidermal growth factor-activated receptor activity;
FLT4	5	positive regulation of cell proliferation; protein binding; cytoplasm; plasma membrane; integral to plasma membrane;
HTR4	5	positive regulation of cell proliferation; G-protein coupled receptor signaling pathway; cytoplasm; plasma membrane; integral to plasma membrane;
PDCD10	5	positive regulation of cell proliferation; protein binding; plasma membrane; protein homodimerization activity; positive regulation of MAP kinase activity;
PRKAA1	5	positive regulation of cell proliferation; signal transduction; protein binding; negative regulation of lipid catabolic process; glucose homeostasis;
TGFBR1	5	positive regulation of cell proliferation; signal transduction; protein binding; plasma membrane; receptor complex;
GABBR2	5	negative regulation of adenylate cyclase activity; G-protein coupled receptor signaling pathway; cytoplasm; plasma membrane; integral to plasma membrane;
ABCA1	5	G-protein coupled receptor signaling pathway; protein binding; plasma membrane; integral to plasma membrane; small molecule metabolic process;
ADRA1A	5	G-protein coupled receptor signaling pathway; signal transduction; plasma membrane; integral to plasma membrane; protein heterodimerization activity;
ADRA1B	5	G-protein coupled receptor signaling pathway; plasma membrane; integral to plasma membrane; protein heterodimerization activity; glucose homeostasis;
BDKRB2	5	G-protein coupled receptor signaling pathway; protein binding; plasma membrane; integral to plasma membrane; protein heterodimerization activity;
CCR5	5	G-protein coupled receptor signaling pathway; protein binding; cytoplasm; plasma membrane; integral to plasma membrane;
CD3E	5	G-protein coupled receptor signaling pathway; protein kinase binding; plasma membrane; integral to plasma membrane; protein heterodimerization activity;
GNG10	5	G-protein coupled receptor signaling pathway; energy reserve metabolic process; signal transduction; plasma membrane; small molecule metabolic process;
HTR1B	5	G-protein coupled receptor signaling pathway; negative regulation of cAMP biosynthetic process; cytoplasm; plasma membrane; integral to plasma membrane;
APC	5	positive regulation of cell migration; protein kinase binding; protein binding; cytoplasm; plasma membrane;
DRD1	5	positive regulation of cell migration; protein binding; plasma membrane; integral to plasma membrane; positive regulation of potassium ion transport;
ENPP1	5	basolateral plasma membrane; protein binding; plasma membrane; protein homodimerization activity; small molecule metabolic process;
SLCO1B3	5	basolateral plasma membrane; cytoplasm; plasma membrane; integral to plasma membrane; small molecule metabolic process;
ARFIP2	5	actin cytoskeleton organization; cellular component movement; protein binding; cytoplasm; plasma membrane;
SLC11A1	5	positive regulation of cytokine production; plasma membrane; integral to plasma membrane; activation of protein kinase activity; protein homodimerization activity;
CACNA1E	5	energy reserve metabolic process; plasma membrane; regulation of insulin secretion; glucose homeostasis; small molecule metabolic process;
APBB1	5	signal transduction; protein binding; cytoplasm; plasma membrane; synapse;
DTNA	5	signal transduction; protein binding; cytoplasm; plasma membrane; synapse;
ADAM8	5	protein binding; cytoplasm; plasma membrane; integral to plasma membrane; positive regulation of membrane protein ectodomain proteolysis;
TPD52L1	5	protein binding; cytoplasm; protein heterodimerization activity; protein homodimerization activity; positive regulation of MAP kinase activity;
SCARB1	5	cytoplasm; plasma membrane; integral to plasma membrane; protein homodimerization activity; small molecule metabolic process;

Genes shared at least 2 KEGG pathways with ADRA2A (count: 0)

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Region: chr10:112836790..112840665 View in gBrowse