DRD4 (D(4) dopamine receptor) variants and mutations
DRD4 (also known as D(4) dopamine receptor) is a human protein-coding gene encoding a d(4) dopamine receptor protein. It modulates dopamine signaling in cortical and limbic circuits and influences cyclic-AMP production and neuronal excitability. Common repeat polymorphisms have been studied extensively for behavioral traits, although their individual effects are modest and not deterministic. This analysis covers 1,211 DRD4 variants and mutations. Of these, 100% have computational variant effect predictions. Disease context includes schizophrenia, Parkinson disease, and bipolar disorder. Example DRD4 variants include p.Gly2 Arg4del, p.Gly2 Asn3insTrp, and G2R.
Variant analysis overview
- Gene: DRD4
- Protein: D(4) dopamine receptor
- UniProt accession: P21917
- Organism: Homo sapiens
- Variants analyzed: 1211
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 854 unspecified-consequence records; 25 in-frame deletions; 4 in-frame insertions; 187 missense variants; 92 synonymous variants; 44 frameshift variants; 1 protein altering variant; 3 stop-gained variants; 1 splice-region variants
- Prediction scores: 1,206 variants have prediction scores (100% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: schizophrenia, Parkinson disease, bipolar disorder, major depressive disorder, restless legs syndrome, Agitation, psychotic disorder, bipolar I disorder, depressive disorder, hypogonadism, hyperprolactinemia, Tourette syndrome.
Protein structure and variant hotspots
- Protein features: 7 transmembrane segments; 4 binding sites; 1 post-translational modification sites.
- Structural context: 422 variants have structural context.
- PTM context: 7 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable DRD4 variants
Examples include p.Gly2 Arg4del, p.Gly2 Asn3insTrp, G2R, G2W, G2E, G2V, G2G, N3H. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- p.Gly2 Arg4del, rs1858078648, gnomAD 11-637307-GGGGAAC, CADD 17.40
- p.Gly2 Asn3insTrp, gnomAD 11-637308-G-GGCT, CADD 17.50
- G2R (p.Gly2Arg), gnomAD 11-637308-G-A, REVEL 0.21, MetaLR 0.28
- G2W (p.Gly2Trp), gnomAD 11-637308-G-T, REVEL 0.25, MetaLR 0.48
- G2E (p.Gly2Glu), gnomAD 11-637309-G-A, REVEL 0.11, MetaLR 0.19
- G2V (p.Gly2Val), gnomAD 11-637309-G-T, REVEL 0.22, MetaLR 0.34
- G2G (p.Gly2Gly), gnomAD 11-637310-G-C, CADD 7.62
- N3H (p.Asn3His), gnomAD rs1858078829, MetaLR 0.22, MetaSVM -0.90
- N3I (p.Asn3Ile), Ensembl rs1437241985, REVEL 0.13, AlphaMissense 0.32
- N3D (p.Asn3Asp), gnomAD 11-637311-A-G, REVEL 0.12, MetaLR 0.18
- N3Y (p.Asn3Tyr), gnomAD 11-637311-A-T, REVEL 0.22, MetaLR 0.19
- N3S (p.Asn3Ser), gnomAD 11-637312-A-G, REVEL 0.14, MetaLR 0.20
- N3K (p.Asn3Lys), gnomAD 11-637313-C-A, REVEL 0.13, MetaLR 0.18
- N3N (p.Asn3Asn), rs1858079025, gnomAD 11-637313-C-T, CADD 7.52
- R4C (p.Arg4Cys), ExAC rs766253519, TOPMed rs766253519, gnomAD rs766253519, REVEL 0.22, AlphaMissense 0.27
- R4G (p.Arg4Gly), ExAC rs766253519, TOPMed rs766253519, gnomAD rs766253519, MetaLR 0.12, MetaSVM -1.04
- R4L (p.Arg4Leu), Ensembl rs1321681323, REVEL 0.09, AlphaMissense 0.12
- R4S (p.Arg4Ser), gnomAD 11-637314-C-A, REVEL 0.07, MetaLR 0.10
- R4H (p.Arg4His), gnomAD 11-637315-G-A, REVEL 0.15, MetaLR 0.15
- R4R (p.Arg4Arg), gnomAD 11-637316-C-A, CADD 8.22
- S5G (p.Ser5Gly), TOPMed rs1404914278, gnomAD rs1404914278, REVEL 0.16, AlphaMissense 0.08
- S5N (p.Ser5Asn), TOPMed rs1391713906, gnomAD rs1391713906, REVEL 0.11, AlphaMissense 0.15
- S5A (p.Ser5Ala), gnomAD 11-637315-GC-G, CADD 22.40
- S5R (p.Ser5Arg), gnomAD 11-637317-AGCACCG, CADD 23.30
- S5C (p.Ser5Cys), gnomAD 11-637317-A-T, REVEL 0.14, MetaLR 0.16
- S5I (p.Ser5Ile), gnomAD 11-637318-G-T, REVEL 0.17, MetaLR 0.20
- S5T (p.Ser5Thr), gnomAD 11-637318-G-C, REVEL 0.07, MetaLR 0.13
- S5S (p.Ser5Ser), gnomAD 11-637319-C-T, CADD 7.90
- T6I (p.Thr6Ile), TOPMed rs1799989297, gnomAD rs1799989297, REVEL 0.10, AlphaMissense 0.17
- T6S (p.Thr6Ser), TOPMed rs1799989297, gnomAD rs1799989297, REVEL 0.13, AlphaMissense 0.07
- p.Thr6 Ala7del, gnomAD 11-637319-CACCGCG, CADD 11.10
- T6A (p.Thr6Ala), gnomAD 11-637320-A-G, REVEL 0.19, MetaLR 0.07
- T6N (p.Thr6Asn), gnomAD 11-637321-C-A, REVEL 0.11, MetaLR 0.16
- T6T (p.Thr6Thr), gnomAD 11-637322-C-G, CADD 1.19
- A7S (p.Ala7Ser), TOPMed rs1411841186, gnomAD rs1411841186, REVEL 0.03, AlphaMissense 0.09
- A7T (p.Ala7Thr), TOPMed rs1411841186, gnomAD rs1411841186, REVEL 0.02, AlphaMissense 0.09
- A7V (p.Ala7Val), TOPMed rs1200081739, gnomAD rs1200081739, REVEL 0.13, AlphaMissense 0.12
- A7P (p.Ala7Pro), gnomAD 11-637323-G-C, REVEL 0.03, MetaLR 0.15
- A7E (p.Ala7Glu), gnomAD 11-637324-C-A, REVEL 0.08, MetaLR 0.15
- A7A (p.Ala7Ala), rs901884594, gnomAD 11-637325-G-A, CADD 5.41
- D8E (p.Asp8Glu), TOPMed rs887057327, gnomAD rs887057327, REVEL 0.11, AlphaMissense 0.09
- D8G (p.Asp8Gly), gnomAD rs1564911613, REVEL 0.10, AlphaMissense 0.06
- D8H (p.Asp8His), TOPMed rs1220195801, gnomAD rs1220195801, REVEL 0.16, AlphaMissense 0.16
- D8N (p.Asp8Asn), TOPMed rs1220195801, gnomAD rs1220195801, REVEL 0.10, AlphaMissense 0.14
- D8A (p.Asp8Ala), gnomAD 11-637311-A-AACCG, CADD 23.60
- p.Asp8 Ala20del, gnomAD 11-637320-ACCGCGG, CADD 14.80
- D8Y (p.Asp8Tyr), gnomAD 11-637326-G-T, REVEL 0.14, MetaLR 0.18
- D8V (p.Asp8Val), gnomAD 11-637327-A-T, REVEL 0.15, MetaLR 0.19
- D8D (p.Asp8Asp), rs887057327, gnomAD 11-637328-C-T, CADD 3.01
- A9T (p.Ala9Thr), Ensembl rs1589956548, REVEL 0.14, AlphaMissense 0.09
- A9V (p.Ala9Val), ExAC rs776606454, TOPMed rs776606454, gnomAD rs776606454, REVEL 0.08, AlphaMissense 0.11
- p.Ala9 Asp10del, rs1165274734, gnomAD 11-637321-CCGCGGA, CADD 14.40
- A9P (p.Ala9Pro), gnomAD 11-637329-G-C, REVEL 0.14, MetaLR 0.20
- A9S (p.Ala9Ser), gnomAD 11-637329-G-T, REVEL 0.12, MetaLR 0.14
- A9E (p.Ala9Glu), gnomAD 11-637330-C-A, REVEL 0.07, MetaLR 0.10
- A9A (p.Ala9Ala), rs941276882, gnomAD 11-637331-G-A, CADD 5.12
- D10E (p.Asp10Glu), TOPMed rs12720386, gnomAD rs12720386, REVEL 0.06, AlphaMissense 0.09
- D10G (p.Asp10Gly), TOPMed rs1858080173, gnomAD rs1858080173, REVEL 0.06, AlphaMissense 0.05
- D10Y (p.Asp10Tyr), NCI-TCGA TCGA novel, MetaLR 0.16, MetaSVM -0.88, Variant assessed as somatic; moderate impact.
- D10H (p.Asp10His), gnomAD 11-637332-G-C, REVEL 0.14, MetaLR 0.16
- D10N (p.Asp10Asn), gnomAD 11-637332-G-A, REVEL 0.10, MetaLR 0.15
- D10D (p.Asp10Asp), rs12720386, gnomAD 11-637334-C-T, CADD 3.50
- G11E (p.Gly11Glu), TOPMed rs1274249349, gnomAD rs1274249349, REVEL 0.07, AlphaMissense 0.09
- G11R (p.Gly11Arg), rs189482961, 1000Genomes rs189482961, ExAC rs189482961, TOPMed rs189482961, REVEL 0.05, AlphaMissense 0.16, Benign, not provided
- G11W (p.Gly11Trp), 1000Genomes rs189482961, ExAC rs189482961, TOPMed rs189482961, gnomAD rs189482961, REVEL 0.10, AlphaMissense 0.14, Benign
- p.Gly11 Gly17del, gnomAD 11-637334-CGGGCTG, CADD 13.90
- G11V (p.Gly11Val), gnomAD 11-637336-G-T, REVEL 0.09, MetaLR 0.14
- G11G (p.Gly11Gly), gnomAD 11-637337-G-A, CADD 6.60
- L12C (p.Leu12Cys), gnomAD 11-637334-CG-C, CADD 13.00
- L12M (p.Leu12Met), gnomAD 11-637338-C-A, REVEL 0.09, MetaLR 0.18
- L12L (p.Leu12Leu), rs1858080491, gnomAD 11-637338-C-T, CADD 6.64
- L12P (p.Leu12Pro), gnomAD 11-637339-T-C, REVEL 0.06, MetaLR 0.18
- L13L (p.Leu13Leu), rs1858080567, gnomAD 11-637341-C-T, CADD 6.02
- L13M (p.Leu13Met), gnomAD 11-637341-C-A, REVEL 0.09, MetaLR 0.31
- L13P (p.Leu13Pro), gnomAD 11-637342-T-C, REVEL 0.23, MetaLR 0.31
- A14T (p.Ala14Thr), gnomAD 11-637344-G-A, REVEL 0.15, MetaLR 0.17
- A14P (p.Ala14Pro), gnomAD 11-637344-G-C, REVEL 0.12, MetaLR 0.32
- A14S (p.Ala14Ser), gnomAD 11-637344-G-T, REVEL 0.14, MetaLR 0.16
- A14V (p.Ala14Val), gnomAD 11-637345-C-T, REVEL 0.04, MetaLR 0.14
- A14D (p.Ala14Asp), gnomAD 11-637345-C-A, REVEL 0.21, MetaLR 0.24
- A14A (p.Ala14Ala), gnomAD 11-637346-T-C, CADD 1.20
- G15E (p.Gly15Glu), TOPMed rs1858080741, REVEL 0.06, AlphaMissense 0.10
- G15W (p.Gly15Trp), gnomAD 11-637347-G-T, REVEL 0.26, MetaLR 0.32
- G15R (p.Gly15Arg), gnomAD 11-637347-G-A, REVEL 0.20, MetaLR 0.11
- G15V (p.Gly15Val), gnomAD 11-637348-G-T, REVEL 0.15, MetaLR 0.14
- G15G (p.Gly15Gly), rs1350588801, gnomAD 11-637349-G-T, CADD 3.81
- R16C (p.Arg16Cys), TOPMed rs1589956563, REVEL 0.10, AlphaMissense 0.40
- R16H (p.Arg16His), TOPMed rs1230103335, gnomAD rs1230103335, REVEL 0.11, AlphaMissense 0.18
- p.Arg16 Gly32del, rs1564911627, gnomAD 11-637339-TGCTGGC, CADD 14.10
- R16S (p.Arg16Ser), gnomAD 11-637350-C-A, REVEL 0.04, MetaLR 0.10
- R16L (p.Arg16Leu), gnomAD 11-637351-G-T, REVEL 0.02, MetaLR 0.09
- R16R (p.Arg16Arg), rs765116919, gnomAD 11-637352-C-T, CADD 3.51
- G17E (p.Gly17Glu), TOPMed rs1016692423, gnomAD rs1016692423, REVEL 0.05, AlphaMissense 0.08
- G17R (p.Gly17Arg), TOPMed rs1004471672, gnomAD rs1004471672, REVEL 0.03, AlphaMissense 0.20
- G17del (p.Gly17del), rs1858080993, gnomAD 11-637350-CGCG-C, CADD 8.63
- G17W (p.Gly17Trp), rs774853371, gnomAD 11-637350-CGCGGGC, CADD 22.40
- G17V (p.Gly17Val), gnomAD 11-637354-G-T, REVEL 0.03, MetaLR 0.11
- G17G (p.Gly17Gly), rs534204857, gnomAD 11-637355-G-A, CADD 6.67
- P18A (p.Pro18Ala), TOPMed rs1858081469, gnomAD rs1858081469, REVEL 0.03, AlphaMissense 0.05
- P18L (p.Pro18Leu), TOPMed rs1478059195, gnomAD rs1478059195, REVEL 0.06, AlphaMissense 0.12
- P18S (p.Pro18Ser), TOPMed rs1858081469, gnomAD rs1858081469, REVEL 0.01, AlphaMissense 0.07
- P18G (p.Pro18Gly), gnomAD 11-637342-TGGCTGG, CADD 23.50
- P18H (p.Pro18His), gnomAD 11-637348-GGCGCGG, CADD 22.10
- P18R (p.Pro18Arg), rs996621902, gnomAD 11-637352-CG-C, CADD 18.80
- p.Pro18 Gly29del, rs1564911643, gnomAD 11-637352-CGGGCCG, CADD 9.82
- P18T (p.Pro18Thr), gnomAD 11-637356-C-A, REVEL 0.03, MetaLR 0.12
- P18Q (p.Pro18Gln), gnomAD 11-637357-C-A, REVEL 0.06, MetaLR 0.09
- P18P (p.Pro18Pro), rs962504136, gnomAD 11-637358-G-A, CADD 5.75
- A19D (p.Ala19Asp), TOPMed rs1406033786, gnomAD rs1406033786, REVEL 0.04, AlphaMissense 0.07
- A19G (p.Ala19Gly), TOPMed rs1406033786, gnomAD rs1406033786, MetaLR 0.10, MetaSVM -1.01
- A19P (p.Ala19Pro), gnomAD rs1858081781, REVEL 0.06, AlphaMissense 0.08
- A19R (p.Ala19Arg), gnomAD 11-637357-CGG-C, CADD 20.40
- A19S (p.Ala19Ser), gnomAD 11-637359-G-T, REVEL 0.07, MetaLR 0.10
- A19T (p.Ala19Thr), gnomAD 11-637359-G-A, REVEL 0.04, MetaLR 0.12
- A19V (p.Ala19Val), gnomAD 11-637360-C-T, REVEL 0.03, MetaLR 0.12
- A19A (p.Ala19Ala), rs890861964, gnomAD 11-637361-C-T, CADD 5.80
- A20V (p.Ala20Val), gnomAD rs998551458, REVEL 0.07, AlphaMissense 0.12
- A20T (p.Ala20Thr), gnomAD 11-637362-G-A, REVEL 0.04, MetaLR 0.09
- A20P (p.Ala20Pro), gnomAD 11-637362-G-C, REVEL 0.06, MetaLR 0.12
- A20E (p.Ala20Glu), gnomAD 11-637363-C-A, REVEL 0.05, MetaLR 0.09
- A20A (p.Ala20Ala), rs1207910293, gnomAD 11-637364-G-A, CADD 2.62
- G21E (p.Gly21Glu), TOPMed rs1031335519, gnomAD rs1031335519, MetaLR 0.11, MetaSVM -0.98
- G21V (p.Gly21Val), TOPMed rs1031335519, gnomAD rs1031335519, REVEL 0.14, AlphaMissense 0.10
- p.Gly21 Ala35del, gnomAD 11-637360-CCGCGGG, CADD 13.70
- G21W (p.Gly21Trp), gnomAD 11-637365-G-T, REVEL 0.16, MetaLR 0.42
- G21A (p.Gly21Ala), gnomAD 11-637366-G-C, REVEL 0.13, MetaLR 0.11
- G21G (p.Gly21Gly), gnomAD 11-637367-G-A, CADD 4.47
- A22H (p.Ala22His), NCI-TCGA TCGA novel, MetaLR 0.14, MetaSVM -0.96, Variant assessed as somatic; high impact.
- A22S (p.Ala22Ser), TOPMed rs1012641552, gnomAD rs1012641552, REVEL 0.05, AlphaMissense 0.07
- A22T (p.Ala22Thr), TOPMed rs1012641552, gnomAD rs1012641552, REVEL 0.04, AlphaMissense 0.09
- A22V (p.Ala22Val), gnomAD rs1451868738, REVEL 0.06, AlphaMissense 0.09
- A22R (p.Ala22Arg), gnomAD 11-637349-G-GCGCG, CADD 19.80
- A22G (p.Ala22Gly), gnomAD 11-637363-C-CG, CADD 19.30
- A22P (p.Ala22Pro), gnomAD 11-637368-G-C, REVEL 0.12, MetaLR 0.14
- A22E (p.Ala22Glu), gnomAD 11-637369-C-A, REVEL 0.06, MetaLR 0.15
- A22A (p.Ala22Ala), gnomAD 11-637370-A-G, CADD 6.17
- S23F (p.Ser23Phe), TOPMed rs1408168512, REVEL 0.13, AlphaMissense 0.17
- S23T (p.Ser23Thr), TOPMed rs1276711137, gnomAD rs1276711137, REVEL 0.11, AlphaMissense 0.08, Uncertain significance, not specified
- S23C (p.Ser23Cys), gnomAD 11-637369-CAT-C, CADD 9.94
- p.Ser23 Ala24del, rs1858082930, gnomAD 11-637370-ATCTGCG, CADD 6.67
- S23L (p.Ser23Leu), rs1382058392, gnomAD 11-637371-TC-T, CADD 16.40
- S23Y (p.Ser23Tyr), gnomAD 11-637372-C-A, REVEL 0.20, MetaLR 0.16
- S23S (p.Ser23Ser), rs956983830, gnomAD 11-637373-T-C, CADD 5.37
- A24T (p.Ala24Thr), TOPMed rs1858083195, REVEL 0.05, AlphaMissense 0.08
- A24V (p.Ala24Val), TOPMed rs1203166260, gnomAD rs1203166260, REVEL 0.11, AlphaMissense 0.10
- p.Ala24 Ala26del, gnomAD 11-637371-TCTGCGG, CADD 7.51
- A24R (p.Ala24Arg), gnomAD 11-637372-CT-C, CADD 9.04
- A24C (p.Ala24Cys), rs1564911675, gnomAD 11-637373-TGCGGGG, CADD 19.40
- A24S (p.Ala24Ser), gnomAD 11-637374-G-T, REVEL 0.04, MetaLR 0.12
- A24G (p.Ala24Gly), rs1858083332, gnomAD 11-637374-GC-G, CADD 15.70
- A24E (p.Ala24Glu), gnomAD 11-637375-C-A, REVEL 0.10, MetaLR 0.12
- A24A (p.Ala24Ala), rs1412049604, gnomAD 11-637376-G-A, CADD 5.14
- G25A (p.Gly25Ala), TOPMed rs1248931429, gnomAD rs1248931429, MetaLR 0.10, MetaSVM -1.04
- G25E (p.Gly25Glu), TOPMed rs1248931429, gnomAD rs1248931429, REVEL 0.04, AlphaMissense 0.11
- G25R (p.Gly25Arg), TOPMed rs1357836963, gnomAD rs1357836963, REVEL 0.06, AlphaMissense 0.19
- G25I (p.Gly25Ile), gnomAD 11-637375-CGGGGG-, CADD 17.20
- G25W (p.Gly25Trp), gnomAD 11-637377-G-T, REVEL 0.12, MetaLR 0.23
- G25V (p.Gly25Val), gnomAD 11-637378-G-T, REVEL 0.03, MetaLR 0.15
- G25G (p.Gly25Gly), gnomAD 11-637379-G-T, CADD 3.92
- A26S (p.Ala26Ser), TOPMed rs1296550152, gnomAD rs1296550152, REVEL 0.13, AlphaMissense 0.07
- A26T (p.Ala26Thr), TOPMed rs1296550152, gnomAD rs1296550152, REVEL 0.10, AlphaMissense 0.08
- A26V (p.Ala26Val), TOPMed rs990101829, gnomAD rs990101829, REVEL 0.05, AlphaMissense 0.09, Uncertain significance, not specified
- p.Ala26 Gly29del, rs1333795820, gnomAD 11-637359-GCCGCGG, CADD 9.27
- A26W (p.Ala26Trp), gnomAD 11-637373-TGCGGGG, CADD 21.90
- A26H (p.Ala26His), gnomAD 11-637375-CG-C, CADD 14.20
- A26E (p.Ala26Glu), gnomAD 11-637381-C-A, REVEL 0.07, MetaLR 0.09
- A26A (p.Ala26Ala), rs762138953, gnomAD 11-637382-A-T, CADD 4.00
- S27C (p.Ser27Cys), rs1022471416, ClinGen CA216942669, ClinVar RCV004269211, TOPMed rs1022471416, REVEL 0.12, AlphaMissense 0.18, Uncertain significance, not specified
- S27F (p.Ser27Phe), TOPMed rs1022471416, gnomAD rs1022471416, Uncertain significance
- S27P (p.Ser27Pro), rs1858083847, ClinGen CA379002427, ClinVar RCV004127147, REVEL 0.06, AlphaMissense 0.06, Uncertain significance, not specified
- S27T (p.Ser27Thr), gnomAD rs1858083847, REVEL 0.06, AlphaMissense 0.08
- S27G (p.Ser27Gly), rs869141319, gnomAD 11-637376-GGGGGCA, CADD 19.90
- S27Y (p.Ser27Tyr), gnomAD 11-637384-C-A, REVEL 0.12, MetaLR 0.15
- S27S (p.Ser27Ser), gnomAD 11-637385-T-C, CADD 3.23
- A28G (p.Ala28Gly), 1000Genomes rs547677287, TOPMed rs547677287, REVEL 0.05, AlphaMissense 0.06
- A28V (p.Ala28Val), 1000Genomes rs547677287, TOPMed rs547677287, REVEL 0.05, AlphaMissense 0.11
- A28del (p.Ala28del), gnomAD 11-637383-TCTG-T, CADD 6.50
- A28S (p.Ala28Ser), gnomAD 11-637386-G-T, REVEL 0.06, MetaLR 0.11
- A28T (p.Ala28Thr), gnomAD 11-637386-G-A, REVEL 0.08, MetaLR 0.12
- A28E (p.Ala28Glu), gnomAD 11-637387-C-A, REVEL 0.05, MetaLR 0.12
Public DRD4 analysis runs
- DRD4 analysis run — DRD4 (1,211 variants) — completed 2026-08-19