DRD4

dopamine receptor D4, the group of Dopamine receptors

Basic information

Region (hg38): 11:637268-640706

Links

ENSG00000069696 ∙ NCBI:1815 ∙ OMIM:126452 ∙ HGNC:3025 ∙ Uniprot:P21917 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DRD4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DRD4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	16		17
missense			70	5	3	78
nonsense						0
start loss						0
frameshift		1	2	1		4
inframe indel			4		2	6
splice donor/acceptor (+/-2bp)						0
splice region				2	1	3
non coding			2			2
Total	0	1	79	22	5

Variants in DRD4

This is a list of pathogenic ClinVar variants found in the DRD4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-637294-C-T		Hereditary attention deficit-hyperactivity disorder	Uncertain significance (-)
11-637335-G-C		DRD4-related disorder	Benign (Aug 01, 2023)
11-637349-GCGCGGGCCGGC-G		Hereditary attention deficit-hyperactivity disorder	Uncertain significance (-)
11-637355-G-A			Likely benign (Jun 23, 2018)
11-637361-CGCGGGGGCATCT-C		DRD4-related disorder	Benign (Oct 31, 2019)
11-637383-T-C		not specified	Uncertain significance (Feb 17, 2022)
11-637384-C-G		not specified	Uncertain significance (Jan 23, 2023)
11-637408-C-T		not specified	Uncertain significance (Dec 14, 2021)
11-637411-C-T		DRD4-related disorder	Uncertain significance (May 01, 2023)
11-637426-G-T		not specified	Uncertain significance (Jun 24, 2022)
11-637430-G-A		DRD4-related disorder	Likely benign (Jun 17, 2019)
11-637443-G-A		not specified	Uncertain significance (Jul 13, 2021)
11-637457-G-GA		Hereditary attention deficit-hyperactivity disorder	Likely pathogenic (Mar 26, 2024)
11-637462-C-G		not specified	Uncertain significance (Dec 22, 2023)
11-637485-A-C		not specified	Uncertain significance (Nov 22, 2021)
11-637491-C-T		not specified	Uncertain significance (Jan 10, 2023)
11-637495-C-T		not specified	Uncertain significance (Sep 25, 2023)
11-637526-G-A		DRD4-related disorder	Benign/Likely benign (Dec 23, 2019)
11-637531-T-C		not specified	Uncertain significance (Jan 23, 2023)
11-637536-G-A		DRD4-related disorder	Likely benign (Oct 02, 2019)
11-637536-GCCGCCGACCTCCT-G		Autonomic nervous system dysfunction • not specified	Conflicting classifications of pathogenicity (Dec 01, 1994)
11-637538-C-T		DRD4-related disorder	Likely benign (Jul 01, 2022)
11-637553-C-T			Likely benign (Oct 22, 2018)
11-637554-G-A		DRD4-related disorder	Benign (Mar 09, 2020)
11-637560-C-A		not specified	Uncertain significance (Aug 12, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DRD4	protein_coding	protein_coding	ENST00000176183	4	3414

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.34e-9	0.0486	121384	0	30	121414	0.000124

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.00	298	215	1.38	0.0000126	2546
Missense in Polyphen		50	38.884	1.2859		377
Synonymous	-5.20	172	104	1.65	0.00000615	975
Loss of Function	-0.722	11	8.70	1.26	3.78e-7	96

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000883	0.0000883
Ashkenazi Jewish	0.00	0.00
East Asian	0.000117	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000487	0.0000446
Middle Eastern	0.000117	0.000109
South Asian	0.000656	0.000654
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 synthetic agonists and drugs (PubMed:9003072, PubMed:16423344, PubMed:27659709, PubMed:29051383). Agonist binding triggers signaling via G proteins that inhibit adenylyl cyclase (PubMed:7512953, PubMed:7643093, PubMed:16423344, PubMed:27659709, PubMed:29051383). Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity). {ECO:0000250|UniProtKB:P51436, ECO:0000269|PubMed:16423344, ECO:0000269|PubMed:1840645, ECO:0000269|PubMed:27659709, ECO:0000269|PubMed:29051383, ECO:0000269|PubMed:7512953, ECO:0000269|PubMed:7643093, ECO:0000269|PubMed:8078498, ECO:0000269|PubMed:9003072}.
• Pathway: Dopaminergic synapse - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics;GPCRs, Other;Nicotine Activity on Dopaminergic Neurons;Common Pathways Underlying Drug Addiction;Olfactory bulb development and olfactory learning;GPCRs, Class A Rhodopsin-like;Monoamine GPCRs;Signaling by GPCR;Signal Transduction;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Dopamine receptors;Amine ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;G alpha (i) signalling events;GPCR signaling-G alpha i;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.399

Haploinsufficiency Scores

• pHI: 0.124
• hipred: Y
• hipred_score: 0.524
• ghis: 0.528

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.695

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Drd4
• Phenotype: homeostasis/metabolism phenotype; vision/eye phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: drd4a
• Affected structure: spinal cord interneuron
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: activation of MAPK activity;behavioral fear response;response to amphetamine;cellular calcium ion homeostasis;G protein-coupled receptor signaling pathway;G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger;adenylate cyclase-inhibiting dopamine receptor signaling pathway;dopamine receptor signaling pathway;chemical synaptic transmission;adult locomotory behavior;positive regulation of sodium:proton antiporter activity;positive regulation of kinase activity;response to histamine;social behavior;regulation of dopamine metabolic process;dopamine metabolic process;fear response;regulation of circadian rhythm;behavioral response to cocaine;behavioral response to ethanol;rhythmic process;arachidonic acid secretion;negative regulation of protein secretion;positive regulation of dopamine uptake involved in synaptic transmission;inhibitory postsynaptic potential;G protein-coupled serotonin receptor signaling pathway;regulation of postsynaptic neurotransmitter receptor internalization;negative regulation of voltage-gated calcium channel activity
• Cellular component: plasma membrane;integral component of plasma membrane;membrane;dendrite;postsynapse;glutamatergic synapse
• Molecular function: dopamine neurotransmitter receptor activity, coupled via Gi/Go;G protein-coupled receptor activity;dopamine neurotransmitter receptor activity;G protein-coupled serotonin receptor activity;protein binding;drug binding;potassium channel regulator activity;SH3 domain binding;neurotransmitter receptor activity;dopamine binding;identical protein binding;metal ion binding;epinephrine binding;norepinephrine binding