Dopamine receptor D4

DRD4
Identifiers
Aliases	DRD4, D4DR, dopamine receptor D4
External IDs	OMIM: 126452; MGI: 94926; HomoloGene: 20215; GeneCards: DRD4; OMA:DRD4 - orthologs
Gene location (Human)
Chr.	Chromosome 11 (human)
End	640,706 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	140,876,377 bp
RNA expression pattern
	Top expressed in
	testicle; ; right uterine tube; ; pituitary gland; ; right hemisphere of cerebellum; ; left ovary; ; anterior pituitary; ; right ovary; ; primary visual cortex; ; sural nerve; ; body of uterus;
	Top expressed in
	neural layer of retina; ; retinal pigment epithelium; ; epithelium of lens; ; decidua; ; seminiferous tubule; ; embryo; ; gastrula; ; embryo; ; iris; ; cumulus cell;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	signal transducer activity; potassium channel regulator activity; SH3 domain binding; identical protein binding; dopamine neurotransmitter receptor activity; G protein-coupled receptor activity; protein binding; dopamine binding; dopamine neurotransmitter receptor activity, coupled via Gi/Go; epinephrine binding; norepinephrine binding; metal ion binding; G protein-coupled serotonin receptor activity; neurotransmitter receptor activity;
Cellular component	integral component of membrane; integral component of plasma membrane; membrane; plasma membrane; postsynapse; glutamatergic synapse; dendrite;
Biological process	response to amphetamine; rhythmic process; arachidonic acid secretion; regulation of circadian rhythm; positive regulation of dopamine uptake involved in synaptic transmission; signal transduction; fear response; dopamine metabolic process; behavioral response to ethanol; behavioral response to cocaine; positive regulation of sodium:proton antiporter activity; cellular calcium ion homeostasis; positive regulation of kinase activity; adult locomotory behavior; inhibitory postsynaptic potential; negative regulation of protein secretion; social behavior; negative regulation of voltage-gated calcium channel activity; regulation of dopamine metabolic process; response to histamine; behavioral fear response; dopamine receptor signaling pathway; G protein-coupled receptor signaling pathway; adenylate cyclase-inhibiting dopamine receptor signaling pathway; regulation of postsynaptic neurotransmitter receptor internalization; G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; chemical synaptic transmission; G protein-coupled serotonin receptor signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	1815
	13491
	ENSG00000069696; ENSG00000276825
	ENSMUSG00000025496
	P21917
	P51436
	NM_000797
	NM_007878
	NP_000788
	NP_031904
	Wikidata
View/Edit Human	View/Edit Mouse

The dopamine receptor D₄ is a dopamine D2-like G protein-coupled receptor encoded by the DRD4 gene on chromosome 11 at 11p15.5.^[5]

The structure of DRD4 has been reported in complex with the antipsychotic drug nemonapride.^[6]

As with other dopamine receptor subtypes, the D₄ receptor is activated by the neurotransmitter dopamine. It is linked to many neurological and psychiatric conditions^[7] including schizophrenia and bipolar disorder,^[8] ADHD,^[9]^[10] addictive behaviors,^[11] Parkinson's disease,^[12] and eating disorders such as anorexia nervosa.^[13] A weak association has been drawn between DRD4 and borderline personality disorder.

It is also a target for drugs which treat schizophrenia and Parkinson's disease.^[14] The D₄ receptor is considered to be D₂-like in which the activated receptor inhibits the enzyme adenylate cyclase, thereby reducing the intracellular concentration of the second messenger cyclic AMP.^[15]

^ ^a ^b ^c ENSG00000276825 GRCh38: Ensembl release 89: ENSG00000069696, ENSG00000276825 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000025496 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Van Tol HH, Bunzow JR, Guan HC, Sunahara RK, Seeman P, Niznik HB, Civelli O (April 1991). "Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine". Nature. 350 (6319): 610–4. Bibcode:1991Natur.350..610V. doi:10.1038/350610a0. PMID 1840645. S2CID 4244670.
^ Wang S, Wacker D, Levit A, Che T, Betz RM, McCorvy JD, Venkatakrishnan AJ, Huang XP, Dror RO, Shoichet BK, Roth BL (October 2017). "D4 dopamine receptor high-resolution structures enable the discovery of selective agonists". Science. 358 (6361): 381–386. Bibcode:2017Sci...358..381W. doi:10.1126/science.aan5468. PMC 5856174. PMID 29051383.
^ Ptácek R, Kuzelová H, Stefano GB (September 2011). "Dopamine D4 receptor gene DRD4 and its association with psychiatric disorders". Medical Science Monitor. 17 (9): RA215–20. doi:10.12659/MSM.881925. PMC 3560519. PMID 21873960.
^ Domschke K (July 2013). "Clinical and molecular genetics of psychotic depression". Schizophrenia Bulletin. 39 (4): 766–75. doi:10.1093/schbul/sbt040. PMC 3686457. PMID 23512949.
^ LaHoste GJ, Swanson JM, Wigal SB, Glabe C, Wigal T, King N, Kennedy JL (May 1996). "Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder". Molecular Psychiatry. 1 (2): 121–4. PMID 9118321.
^ Smalley SL, Bailey JN, Palmer CG, Cantwell DP, McGough JJ, Del'Homme MA, Asarnow JR, Woodward JA, Ramsey C, Nelson SF (September 1998). "Evidence that the dopamine D4 receptor is a susceptibility gene in attention deficit hyperactivity disorder". Molecular Psychiatry. 3 (5): 427–30. doi:10.1038/sj.mp.4000457. PMID 9774776.
^ McGeary J (September 2009). "The DRD4 exon 3 VNTR polymorphism and addiction-related phenotypes: a review". Pharmacology Biochemistry and Behavior. 93 (3): 222–9. doi:10.1016/j.pbb.2009.03.010. PMC 2706302. PMID 19336242.
^ Cormier F, Muellner J, Corvol JC (April 2013). "Genetics of impulse control disorders in Parkinson's disease". Journal of Neural Transmission. 120 (4): 665–71. doi:10.1007/s00702-012-0934-4. PMID 23232665. S2CID 21967333.
^ Rask-Andersen M, Olszewski PK, Levine AS, Schiöth HB (March 2010). "Molecular mechanisms underlying anorexia nervosa: focus on human gene association studies and systems controlling food intake". Brain Research Reviews. 62 (2): 147–64. doi:10.1016/j.brainresrev.2009.10.007. PMID 19931559. S2CID 37635456.
^ Ptáček R, Kuželová H, Stefano GB, Raboch J, Kream RM (April 2013). "Targeted D4 dopamine receptors: implications for drug discovery and therapeutic development". Current Drug Targets. 14 (4): 507–12. doi:10.2174/1389450111314040012. PMID 23469923.
^ Neve KA, Seamans JK, Trantham-Davidson H (August 2004). "Dopamine receptor signaling". Journal of Receptor and Signal Transduction Research. 24 (3): 165–205. CiteSeerX 10.1.1.465.5011. doi:10.1081/RRS-200029981. PMID 15521361. S2CID 12407397.

[refGRCh38Ensembl-1] ENSG00000276825 GRCh38: Ensembl release 89: ENSG00000069696, ENSG00000276825 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000025496 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid1840645-5] Van Tol HH, Bunzow JR, Guan HC, Sunahara RK, Seeman P, Niznik HB, Civelli O (April 1991). "Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine". Nature. 350 (6319): 610–4. Bibcode:1991Natur.350..610V. doi:10.1038/350610a0. PMID 1840645. S2CID 4244670.

[6] Wang S, Wacker D, Levit A, Che T, Betz RM, McCorvy JD, Venkatakrishnan AJ, Huang XP, Dror RO, Shoichet BK, Roth BL (October 2017). "D4 dopamine receptor high-resolution structures enable the discovery of selective agonists". Science. 358 (6361): 381–386. Bibcode:2017Sci...358..381W. doi:10.1126/science.aan5468. PMC 5856174. PMID 29051383.

[7] Ptácek R, Kuzelová H, Stefano GB (September 2011). "Dopamine D4 receptor gene DRD4 and its association with psychiatric disorders". Medical Science Monitor. 17 (9): RA215–20. doi:10.12659/MSM.881925. PMC 3560519. PMID 21873960.

[8] Domschke K (July 2013). "Clinical and molecular genetics of psychotic depression". Schizophrenia Bulletin. 39 (4): 766–75. doi:10.1093/schbul/sbt040. PMC 3686457. PMID 23512949.

[9] LaHoste GJ, Swanson JM, Wigal SB, Glabe C, Wigal T, King N, Kennedy JL (May 1996). "Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder". Molecular Psychiatry. 1 (2): 121–4. PMID 9118321.

[10] Smalley SL, Bailey JN, Palmer CG, Cantwell DP, McGough JJ, Del'Homme MA, Asarnow JR, Woodward JA, Ramsey C, Nelson SF (September 1998). "Evidence that the dopamine D4 receptor is a susceptibility gene in attention deficit hyperactivity disorder". Molecular Psychiatry. 3 (5): 427–30. doi:10.1038/sj.mp.4000457. PMID 9774776.

[11] McGeary J (September 2009). "The DRD4 exon 3 VNTR polymorphism and addiction-related phenotypes: a review". Pharmacology Biochemistry and Behavior. 93 (3): 222–9. doi:10.1016/j.pbb.2009.03.010. PMC 2706302. PMID 19336242.

[12] Cormier F, Muellner J, Corvol JC (April 2013). "Genetics of impulse control disorders in Parkinson's disease". Journal of Neural Transmission. 120 (4): 665–71. doi:10.1007/s00702-012-0934-4. PMID 23232665. S2CID 21967333.

[13] Rask-Andersen M, Olszewski PK, Levine AS, Schiöth HB (March 2010). "Molecular mechanisms underlying anorexia nervosa: focus on human gene association studies and systems controlling food intake". Brain Research Reviews. 62 (2): 147–64. doi:10.1016/j.brainresrev.2009.10.007. PMID 19931559. S2CID 37635456.

[14] Ptáček R, Kuželová H, Stefano GB, Raboch J, Kream RM (April 2013). "Targeted D4 dopamine receptors: implications for drug discovery and therapeutic development". Current Drug Targets. 14 (4): 507–12. doi:10.2174/1389450111314040012. PMID 23469923.

[pmid15521361-15] Neve KA, Seamans JK, Trantham-Davidson H (August 2004). "Dopamine receptor signaling". Journal of Receptor and Signal Transduction Research. 24 (3): 165–205. CiteSeerX 10.1.1.465.5011. doi:10.1081/RRS-200029981. PMID 15521361. S2CID 12407397.

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