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FLASH GENE

Symbol

DRD4

contributors: mct/npt - updated : 06-02-2018

HGNC name	dopamine receptor D4
HGNC id	3025

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000797 4 - 1360 NP_000788 - 419 - 2017 29051383

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular vessel artery       Homo sapiens Nervous brain       moderately Visual eye

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	fetal eyes, lens, eye anterior segment, optic nerve, retina, retina foveal and macular, RPE and Choroid

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

seven transmembrane segments (7TM) receptor

HOMOLOGY

Homologene

FAMILY	G-protein coupled receptor 1 family
	D2-like receptor family

CATEGORY

receptor membrane G

SUBCELLULAR LOCALIZATION

plasma membrane

basic FUNCTION	dopamine receptor D4, with high affinity for antagonist clozapine
	stimulating the DRD4 is likely essential in maintaining the normal rhythmic production of ADCY1 from transcript to enzyme activity
	putative involvement of SLC6A3 and DRD4 genes in the aetiology of ADHD with a main role in modulation of key dimensions of the disorder
	regulatory role of DRD4 on AGTR1 expression and function in in the vascular smooth muscle cell (VSMC)
	plays an essential role in cAMP regulation and gap junctional coupling in the photoreceptors, where DRD4 expression is under circadian control
	DRD4, requires two arrestins for desensitization and internalization, and opens up the possibility that other G-protein coupled receptors may require more than one arrestin for desensitization and/or internalization
	DRD4 is a moderator of childrearing effects on the development of disorganized attachment

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

neurotransmission

a component

INTERACTION

DNA

RNA

small molecule

protein	KLHL12 is a novel interaction partner of the DRD4 that functions as an adaptor in a CUL3-based E3 ubiquitin ligase complex to target the receptor for ubiquitination
	inhibit proliferation and migration of vascular smooth muscle cells induced by insulin via down-regulation of insulin receptor expression
	KLHL12, a BTB-Kelch protein, specifically interacts with the polymorphic repeats of the DRD4 and enhances its ubiquitination, which, however, has no influence on receptor degradation
	KLHL12 strongly promotes ubiquitination of the two- and four-repeat variant but has hardly any effect on ubiquitination of the seven-repeat DRD4
	ARRB1, ARRB2 bind constitutively to the most common DRD4 polymorphic variants and to KLHL12 and all three proteins can interact within a single macromolecular complex

cell & other

REGULATION

Other

palmitoylation of the C-terminal tail of DRD4 is required for surface expression, endocytosis, and signaling

ASSOCIATED DISORDERS

corresponding disease(s)

PTNS

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   by hypermethylation, DRD4 promoter methylation was significantly higher in AD patients than in controls

Susceptibility

to Gilles de la Tourette syndrome and a wide range of neuropsychiatric disorders to attention deficit hyperactivity disorder (ADHD), with preferential transmission of paternal alleles to dyslexia (DYX7) to migraine without aura to attention-deficit/hyperactivity disorder (ADHD) related to oxidative stress to schizophrenia to age related changes in brain glucose metabolism

Variant & Polymorphism repeat , other	association with seven repeat allele (VNTR) in exon 3 in attention deficit hyperactivity syndrome
	exon 3 VNTR allele protecting against migraine without aura (DeSousa 2007)
	carriers of the 7R allele appear to be less sensitive to the effects of age on brain glucose metabolism
	male-specific association between DRD4 gene methylation and schizophrenia
	DRD4 GG genotype, that had been exposed to high DMP levels (more than the median), and had high HNE-MA levels had a significantly increased risk for developing ADHD

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cardiovascular aquired   may be a potential therapeutic target to reduce the effects of insulin on artery remodeling

ANIMAL & CELL MODELS

	Drd4 knock-out mice, when compared with wild-type and heterozygous mice, displayed a 7-9.7p100 decrease in lifespan, reduced spontaneous locomotor activity, and no lifespan increase when reared in an enriched environment
	expression of the gene Adcy1, is downregulated in mice lacking Drd4