DRD4
dopamine receptor D4, the group of Dopamine receptors
Basic information
Region (hg38): 11:637269-640706
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (133 variants)
- not_provided (27 variants)
- DRD4-related_disorder (25 variants)
- Hereditary_attention_deficit-hyperactivity_disorder (13 variants)
- DRD4_POLYMORPHISM (1 variants)
- AUTONOMIC_NERVOUS_SYSTEM_DYSFUNCTION (1 variants)
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. These statistics are base on transcript: NM_000000797.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 20 | 23 | ||||
| missense | 136 | 145 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 6 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 1 | 140 | 27 | 6 |
Highest pathogenic variant AF is 0.00000506029
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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