DRD4 (dopamine receptor D4)

Gene

• Entrez ID: 1815
• Gene name: Dopamine receptor D4
• Gene symbol: DRD4
• Synonyms: D4DR
• Chromosome: 11
• Chromosome location: 11p15.5
• Summary: This gene encodes the D4 subtype of the dopamine receptor. The D4 subtype is a G-protein coupled receptor which inhibits adenylyl cyclase. It is a target for drugs which treat schizophrenia and Parkinson disease. Mutations in this gene have been associate

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs587776842	GCCGACCTCCTCC>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT022474	hsa-miR-124-3p	Microarray	18668037
MIRT2519495	hsa-miR-125a-5p	CLIP-seq
MIRT2519496	hsa-miR-125b	CLIP-seq
MIRT2519497	hsa-miR-133a	CLIP-seq
MIRT2519498	hsa-miR-133b	CLIP-seq
MIRT2519499	hsa-miR-3187-3p	CLIP-seq
MIRT2519500	hsa-miR-3189-3p	CLIP-seq
MIRT2519501	hsa-miR-4281	CLIP-seq
MIRT2519502	hsa-miR-4319	CLIP-seq
MIRT2519503	hsa-miR-4529-5p	CLIP-seq
MIRT2519504	hsa-miR-4649-3p	CLIP-seq
MIRT2519505	hsa-miR-4732-3p	CLIP-seq
MIRT2519506	hsa-miR-544b	CLIP-seq
MIRT2519507	hsa-miR-670	CLIP-seq
MIRT2519495	hsa-miR-125a-5p	CLIP-seq
MIRT2519496	hsa-miR-125b	CLIP-seq
MIRT2519497	hsa-miR-133a	CLIP-seq
MIRT2519498	hsa-miR-133b	CLIP-seq
MIRT2519499	hsa-miR-3187-3p	CLIP-seq
MIRT2519500	hsa-miR-3189-3p	CLIP-seq
MIRT2519501	hsa-miR-4281	CLIP-seq
MIRT2519502	hsa-miR-4319	CLIP-seq
MIRT2519503	hsa-miR-4529-5p	CLIP-seq
MIRT2519504	hsa-miR-4649-3p	CLIP-seq
MIRT2519505	hsa-miR-4732-3p	CLIP-seq
MIRT2519506	hsa-miR-544b	CLIP-seq
MIRT2519507	hsa-miR-670	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000187	Process	Activation of MAPK activity	IDA	9843378, 15755724
GO:0001591	Function	Dopamine neurotransmitter receptor activity, coupled via Gi/Go	IDA	1840645, 9003072
GO:0001591	Function	Dopamine neurotransmitter receptor activity, coupled via Gi/Go	IMP	27659709
GO:0001591	Function	Dopamine neurotransmitter receptor activity, coupled via Gi/Go	ISS
GO:0001662	Process	Behavioral fear response	NAS	12860355
GO:0001963	Process	Synaptic transmission, dopaminergic	IEA
GO:0001975	Process	Response to amphetamine	ISS
GO:0004952	Function	Dopamine neurotransmitter receptor activity	IDA	8413587
GO:0004993	Function	G protein-coupled serotonin receptor activity	IBA	21873635
GO:0005515	Function	Protein binding	IPI	12297500, 21184734, 22723743, 32814053
GO:0005886	Component	Plasma membrane	IDA	20531939
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IBA	21873635
GO:0005887	Component	Integral component of plasma membrane	IDA	8413587, 9003072, 9843378, 15755724, 27659709
GO:0006874	Process	Cellular calcium ion homeostasis	IC	7921596
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007187	Process	G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	IBA	21873635
GO:0007195	Process	Adenylate cyclase-inhibiting dopamine receptor signaling pathway	IDA	7512953, 9003072, 9843378
GO:0007195	Process	Adenylate cyclase-inhibiting dopamine receptor signaling pathway	IMP	27659709
GO:0007212	Process	Dopamine receptor signaling pathway	IDA	1840645
GO:0007268	Process	Chemical synaptic transmission	IBA	21873635
GO:0008344	Process	Adult locomotory behavior	ISS
GO:0015459	Function	Potassium channel regulator activity	NAS	12297500
GO:0016020	Component	Membrane	IDA	7512953
GO:0017124	Function	SH3 domain binding	IDA	9843378
GO:0030425	Component	Dendrite	IBA	21873635
GO:0030594	Function	Neurotransmitter receptor activity	IBA	21873635
GO:0032417	Process	Positive regulation of sodium:proton antiporter activity	IDA	7512953
GO:0033674	Process	Positive regulation of kinase activity	IDA	15755724
GO:0034776	Process	Response to histamine	IDA	16839358
GO:0035176	Process	Social behavior	NAS	11126393, 11409696
GO:0035240	Function	Dopamine binding	IDA	1319557, 9003072
GO:0042053	Process	Regulation of dopamine metabolic process	ISS
GO:0042417	Process	Dopamine metabolic process	IC	1840645
GO:0042596	Process	Fear response	ISS
GO:0042752	Process	Regulation of circadian rhythm	ISS
GO:0042802	Function	Identical protein binding	IPI	21184734, 21320289
GO:0046872	Function	Metal ion binding	IEA
GO:0048148	Process	Behavioral response to cocaine	ISS
GO:0048149	Process	Behavioral response to ethanol	TAS	12888781
GO:0048511	Process	Rhythmic process	IEA
GO:0050482	Process	Arachidonic acid secretion	IDA	7512953
GO:0050709	Process	Negative regulation of protein secretion	IDA	16839358
GO:0051379	Function	Epinephrine binding	IDA	9003072
GO:0051380	Function	Norepinephrine binding	IDA	9003072
GO:0051586	Process	Positive regulation of dopamine uptake involved in synaptic transmission	IC	1840645
GO:0060080	Process	Inhibitory postsynaptic potential	ISS
GO:0098664	Process	G protein-coupled serotonin receptor signaling pathway	IEA
GO:0098794	Component	Postsynapse	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0099149	Process	Regulation of postsynaptic neurotransmitter receptor internalization	IEA
GO:1901386	Process	Negative regulation of voltage-gated calcium channel activity	IDA	7921596

Other IDs

• MIM: 126452
• HGNC: 3025
• e!Ensembl: ENSG00000069696

Protein

• UniProt ID: P21917
• Protein name: D(4) dopamine receptor (D(2C) dopamine receptor) (Dopamine D4 receptor)
• Protein function: Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Activated by dopamine, but also by epinephrine and norepinephrine, and by numerous synt
• PDB: 5WIU, 5WIV
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00001	7tm_1	51 → 400	7 transmembrane receptor (rhodopsin family)	Family

• Sequence:

  MGNRSTADADGLLAGRGPAAGASAGASAGLAGQGAAALVGGVLLIGAVLAGNSLVCVSVA
  TERALQTPTNSFIVSLAAADLLLALLVLPLFVYSEVQGGAWLLSPRLCDALMAMDVMLCT
  ASIFNLCAISVDRFVAVAVPLRYNRQGGSRRQLLLIGATWLLSAAVAAPVLCGLNDVRGR
  DPAVCRLEDRDYVVYSSVCSFFLPCPLMLLLYWATFRGLQRWEVARRAKLHGRAPRRPSG
  PGPPSPTPPAPRLPQDPCGPDCAPPAPGLPRGPCGPDCAPAAPSLPQDPCGPDCAPPAPG
  LPPDPCGSNCAPPDAVRAAALPPQTPPQTRRRRRAKITGRERKAMRVLPVVVGAFLLCWT
  PFFVVHITQALCPACSVPPRLVSAVTWLGYVNSALNPVIYTVFNAEFRNVFRKALRACC

• Sequence length: 419

Pathways

KEGG:

Neuroactive ligand-receptor interaction
Hormone signaling
Dopaminergic synapse

Reactome:

Dopamine receptors
G alpha (i) signalling events

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Attention deficit hyperactivity disorder	Attention Deficit Disorder, Attention deficit hyperactivity disorder	rs120074176, rs786205019	14699430, 14699433, 29054088, 17671965, 29054088, 14699430, 14699433, 17671965
Autism spectrum disorder	Pervasive Development Disorder	rs724159978, rs75184679, rs119103221, rs9332964, rs121912562, rs1594344233, rs727504317, rs111033204, rs1801086, rs587784464, rs724159948, rs764659822, rs794727977, rs796052733, rs796052728, rs762292772, rs864321694, rs869312878, rs758432471, rs750896617, rs886039692, rs886039770, rs201037487, rs200483989, rs1057518198, rs1057517708, rs780267761, rs1555910143, rs1057519632, rs775225727, rs751037529, rs1064794848, rs1064795655, rs1131691548, rs1135401811, rs1553248081, rs1454466097, rs1554480537, rs1553578503, rs1553518509, rs774152851, rs1554481395, rs1554464807, rs1554401434, rs1452048149, rs370498156, rs756691187, rs1557863430, rs1557863440, rs1557863546, rs769581210, rs202098093, rs1276388879, rs778792467, rs760059077, rs373783340, rs1557867853, rs772572695, rs753214391, rs749270162, rs548226228, rs1557870645, rs1557874046, rs749548928, rs754532606, rs1557901347, rs1557902023, rs1557909572, rs574335012, rs1557909821, rs1372713010, rs561369202, rs1476293577, rs1557910728, rs1557911386, rs375045125, rs998675361, rs1557916296, rs1557935477, rs866632178, rs1561824498, rs1396313317, rs1564801388, rs1564801473, rs1564950387, rs1565527302, rs1569513495, rs1569305431, rs143944436, rs1563183492, rs1561846159, rs1565819425, rs1562957809, rs1585645641, rs1585016242, rs1595127294, rs1585667374, rs1585653028, rs1585653240, rs1592919048, rs1585645384, rs1789927813	20731709
Schizophrenia	Schizophrenia	rs74315508, rs74315509, rs13447324, rs1558507406, rs387906932, rs387906933, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	18583979

Unknown
Disease name	Disease term	dbSNP ID	References
Bipolar disorder	Bipolar Disorder		15627807, 15860340, 22543114, 25233244, 18332878
Development disorder	Child Development Disorders, Pervasive		20731709
Disruptive behavior disorder	Disruptive Behavior Disorder		20731709
Mental depression	Mental Depression, Depressive disorder, Unipolar Depression, Major Depressive Disorder	rs587778876, rs587778877	23512949, 23627963, 22607734, 25011686, 23796967, 23512949, 25011686, 23796967, 23627963, 22607734, 17938638, 16756688, 10512150, 10483058, 20558238, 10512150, 17938638, 10483058, 16756688, 20558238
Minimal brain dysfunction	Minimal Brain Dysfunction		29054088, 14699433, 17671965, 14699430
Mood disorder	Dysphoric mood, Mood Disorders		14560322, 15627807, 15860340, 16319504, 16756688, 15288435
Motor tic disorders	Motor Tic Disorders		20731709
Oppositional defiant disorder	Oppositional Defiant Disorder		20731709
Seasonal affective disorder	Seasonal Affective Disorder		16760922, 14560322, 15522250, 20336060
Separation anxiety disorder	Separation Anxiety Disorder		20731709
Tic disorder	Tic disorder, Tic Disorders, Vocal, Childhood Tic Disorders		20731709
Transient tic disorder	Transient Tic Disorder		20731709