DRD3

dopamine receptor D3, the group of Dopamine receptors

Basic information

Region (hg38): 3:114127579-114199407

Links

ENSG00000151577 ∙ NCBI:1814 ∙ OMIM:126451 ∙ HGNC:3024 ∙ Uniprot:P35462 ∙ 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 DRD3 gene.

• Tremor, hereditary essential, 1 (14 variants)
• not provided (11 variants)
• Hereditary essential tremor (10 variants)
• Inborn genetic diseases (8 variants)
• not specified (3 variants)
• DRD3-related condition (1 variants)
• Essential tremor, susceptibility to (1 variants)
• Schizophrenia, susceptibility to (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DRD3 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				7	3	10
missense			13	5		18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			3			3
non coding			5	4	4	13
Total	0	0	18	16	7

Variants in DRD3

This is a list of pathogenic ClinVar variants found in the DRD3 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-114128768-G-T		Hereditary essential tremor	Uncertain significance (Jun 14, 2016)
3-114128809-C-A		DRD3-related disorder	Uncertain significance (Mar 21, 2023)
3-114128842-G-A		Tremor, hereditary essential, 1	Benign/Likely benign (Aug 01, 2022)
3-114128872-A-G			Likely benign (Nov 01, 2022)
3-114128901-C-A		not specified	Uncertain significance (Aug 17, 2021)
3-114131137-T-C		Tremor, hereditary essential, 1	Benign (Dec 31, 2019)
3-114131170-C-T			Likely benign (May 31, 2018)
3-114131184-G-T		not specified	Uncertain significance (Dec 14, 2021)
3-114131203-C-A			Likely benign (Jul 20, 2018)
3-114131303-C-T		Hereditary essential tremor	Uncertain significance (Jun 14, 2016)
3-114131379-G-A		not specified	Uncertain significance (Dec 28, 2023)
3-114139496-T-C			Uncertain significance (Jul 01, 2022)
3-114139503-C-T		Tremor, hereditary essential, 1	Benign (Jan 13, 2018)
3-114139503-C-C			Benign (Dec 31, 2019)
3-114139532-A-T		Tremor, hereditary essential, 1 • DRD3-related disorder	Likely benign (May 09, 2022)
3-114139547-G-C		not specified	Uncertain significance (Feb 28, 2023)
3-114139564-C-T		not specified	Uncertain significance (Jun 16, 2023)
3-114139600-T-C		not specified	Uncertain significance (Dec 19, 2023)
3-114139694-C-T		not specified	Uncertain significance (Jan 31, 2024)
3-114147535-C-T		Tremor, hereditary essential, 1	Likely benign (Jan 13, 2018)
3-114147536-G-A			Likely benign (Dec 01, 2023)
3-114147537-G-T		Tremor, hereditary essential, 1	Uncertain significance (Jul 01, 2022)
3-114157428-G-A		not specified	Benign (Mar 09, 2018)
3-114159748-G-A		Hereditary essential tremor	Uncertain significance (Jun 14, 2016)
3-114159773-C-T		not specified	Uncertain significance (Nov 22, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DRD3	protein_coding	protein_coding	ENST00000383673	6	70756

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00237	0.983	125729	0	18	125747	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.47	169	232	0.728	0.0000133	2560
Missense in Polyphen		61	98.94	0.61653		1099
Synonymous	-0.0948	96	94.8	1.01	0.00000538	847
Loss of Function	2.13	7	16.3	0.429	8.27e-7	185

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000427	0.000427
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000807	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation. {ECO:0000269|PubMed:19520868}.
• Disease: DISEASE: Tremor, hereditary essential 1 (ETM1) [MIM:190300]: A common movement disorder mainly characterized by postural tremor of the arms. Head, legs, trunk, voice, jaw, and facial muscles also may be involved. The condition can be aggravated by emotions, hunger, fatigue and temperature extremes, and may cause a functional disability or even incapacitation. Inheritance is autosomal dominant. {ECO:0000269|PubMed:16650084, ECO:0000269|PubMed:16809426}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Schizophrenia (SCZD) [MIM:181500]: A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. {ECO:0000269|PubMed:1362221, ECO:0000269|PubMed:9514583}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.
• 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;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: 0.361

Intolerance Scores

• loftool: 0.706
• rvis_EVS: -0.36
• rvis_percentile_EVS: 29.16

Haploinsufficiency Scores

• pHI: 0.219
• hipred: Y
• hipred_score: 0.714
• ghis: 0.428

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.933

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Drd3
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; digestive/alimentary phenotype; 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); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;synaptic transmission, dopaminergic;response to amphetamine;regulation of blood volume by renin-angiotensin;G protein-coupled receptor internalization;cellular calcium ion homeostasis;autophagy;G protein-coupled receptor signaling pathway;adenylate cyclase-modulating G protein-coupled receptor signaling pathway;adenylate cyclase-activating dopamine receptor signaling pathway;adenylate cyclase-inhibiting dopamine receptor signaling pathway;learning or memory;learning;locomotory behavior;positive regulation of cell population proliferation;visual learning;regulation of dopamine secretion;regulation of lipid metabolic process;negative regulation of sodium:proton antiporter activity;positive regulation of cytokinesis;circadian regulation of gene expression;response to histamine;social behavior;gastric emptying;positive regulation of renal sodium excretion;regulation of multicellular organism growth;response to cocaine;dopamine metabolic process;response to drug;negative regulation of apoptotic process;response to morphine;regulation of circadian sleep/wake cycle, sleep;response to ethanol;negative regulation of blood pressure;positive regulation of mitotic nuclear division;positive regulation of transcription by RNA polymerase II;acid secretion;behavioral response to cocaine;negative regulation of oligodendrocyte differentiation;arachidonic acid secretion;negative regulation of protein secretion;musculoskeletal movement, spinal reflex action;regulation of dopamine uptake involved in synaptic transmission;negative regulation of protein kinase B signaling;prepulse inhibition;negative regulation of dopamine receptor signaling pathway;positive regulation of dopamine receptor signaling pathway;adenylate cyclase-activating adrenergic receptor signaling pathway;regulation of locomotion involved in locomotory behavior;regulation of postsynaptic neurotransmitter receptor internalization
• Cellular component: plasma membrane;integral component of plasma membrane;endocytic vesicle;cell projection;apical part of cell;dopaminergic synapse;glutamatergic synapse;GABA-ergic synapse;integral component of postsynaptic density membrane
• Molecular function: dopamine neurotransmitter receptor activity, coupled via Gi/Go;adrenergic receptor activity;protein binding;drug binding;protein domain specific binding;D1 dopamine receptor binding;dopamine binding