The DOI matches its Crossref record; 19 of the 20 references it cites were found in a registry or an index.
Multiple dopamine D4 receptor variants in the human population
Abstract
The dopamine D4 receptor structurally and pharmacologically resembles the dopamine D2 and D3 receptors. Clozapine, an atypical antipsychotic that is relatively free of the adverse effects of drug-induced parkinsonism and tardive dyskinesia, binds to the D4 receptor with an affinity 10 times higher than to the D2 and D3 receptors. This may explain clozapine's atypical properties. Here we report the existence of at least three polymorphic variations in the coding sequence of the human D4 receptor. A 48-base-pair sequence in the putative third cytoplasmic loop of this receptor exists either as a direct-repeat sequence (D4.2), as a fourfold repeat (D4.4) or as a sevenfold repeat (D4.7). Two more variant alleles were detected in humans. Expression of the complementary DNA for the three cloned receptor variants showed different properties for the long form (D4.7) and the shorter forms (D4.2, D4.4) with respect to clozapine and spiperone binding. To our knowledge, this is the first report of a receptor in the catecholamine receptor family that displays polymorphic variation in the human population. Such variation among humans may underlie individual differences in susceptibility to neuropsychiatric disease and in responsiveness to antipsychotic medication.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Functional significance of this polymorphism has been demonstrated [70–75].”
From Genetics of child aggression, a systematic review (2024) · cites this paper as [70]
Citations
Cites
Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
Chomczynski, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1006/abio.1987.9999 · Cited by 65,515
A simple and very efficient method for generating cDNA libraries
Gubler, U., & Hoffman, B. J. (1983) · Gene · doi:10.1016/0378-1119(83)90230-5 · Cited by 4,461
Clozapine for the Treatment-Resistant Schizophrenic: A Double-blind Comparison With Chlorpromazine
Kane, J. (1988) · Archives of General Psychiatry · doi:10.1001/archpsyc.1988.01800330013001 · Cited by 4,156
A catalogue of splice junction sequences
Mount, S. M. (1982) · Nucleic Acids Research · doi:10.1093/nar/10.2.459 · Cited by 3,742
Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy
Spada, A. L., Wilson, E. M., Lubahn, D. B., Harding, A., & Fischbeck, K. (1991) · Nature · doi:10.1038/352077a0 · Cited by 2,801
Brook, J. D., McCurrach, M. E., Harley, H. G., Buckler, A., Church, D. M., Aburatani, H., Hunter, K. W., Stanton, V. P., Thirion, J., Hudson, T. J., et al. (1992) · Cell · doi:10.1016/0092-8674(92)90154-5 · Cited by 2,754
Sokoloff, P., Bruno Giros, A., Martres, M., Bouthenet, M.-L., & Schwartz, J. (1990) · Nature · doi:10.1038/347146a0 · Cited by 2,608
McMaster, G. K., & Carmichael, G. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.11.4835 · Cited by 2,406
Tol, H. H. M. V., Bunzow, J. R., Guan, H., Sunahara, R. K., Seeman, P. M., Niznik, H. B., & Civelli, O. (1991) · Nature · doi:10.1038/350610a0 · Cited by 2,015
Self-citationInstability of a 550-Base Pair DNA Segment and Abnormal Methylation in Fragile X Syndrome
Oberlé, I., Rousseau, F., Heitz, D., Kretz, C., Devys, D., Hanauer, A., Boué, J., Bertheas, M. F., & Mandel, J. L. (1991) · Science · doi:10.1126/science.252.5009.1097 · Cited by 1,499
Flagged first, then by citations
1 of the 20 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
- Chomczynski, P. & Sacchi, N. Analyt. Biochem. 162, 156–159 (1987). · DOI
- Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning (Cold Spring Harbor Laboratory Press, New York, 1989).
- Budowle, B. & Baechtel, F. S. Appl. theoret. Electrophoresis (in the press).
Cited by
Sorted by citations
Items 801–900 of 960
Stendel, M. S., Ramstead, M. J. D., & Veissière, S. P. L. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108695374.026 · Cited by 2
van der Westhuizen, E. T. (2023) · British Journal of Pharmacology · doi:10.1111/bph.16057 · Cited by 2
Chaki, S., Nakazato, A., & Okuyama, S. (2000) · CNS Drug Reviews · doi:10.1111/j.1527-3458.2000.tb00140.x · Cited by 2
Recombinant protein expression in a Drosophila cell line: comparison with the baculovirus system
Bernard, A. R., Kost, T. A., Overton, L. K., Cavegn, C., Young, J., Bertrand, M., Yahia-Cherif, Z., Chabert, C., & Mills, A. (1994) · Current applications of cell culture engineering · doi:10.1007/978-94-011-0257-5_16 · Cited by 2
Mueller, K. L., Murray, J. C., Duff, M., Pennington, B. F., Zubrowski, P., & Tomblin, J. B. (2012) · doi:10.17077/etd.dfynfxnz · Cited by 2
Changes in Research and Development of Medicinal Products since the Paediatric Regulation
Ceci, A., Catapano, M., Manfredi, C., Wong, I. C. K., Orlu, M., Meneguz, A., Baiardi, P., Pasqua, O. E. D., Iolascon, A., Scarpa, M., et al. (2011) · InTech eBooks · doi:10.5772/28797 · Cited by 1
The Neural Mechanisms Underlying Social Norms
Mu, Y., & Gelfand, M. J. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108695374.015 · Cited by 2
Yang, J. J., Wang, Z., Trucco, E. M., Buu, A., & Lin, H. (2021) · The American Journal of Drug and Alcohol Abuse · doi:10.1080/00952990.2021.1977311 · Cited by 1
Jamnik, M. R., & DiLalla, L. F. (2023) · Developmental Psychobiology · doi:10.1002/dev.22387 · Cited by 1
Jiang, H., Zhang, J., Li, Q., & Zhou, Y. (2024) · Medicine · doi:10.1097/md.0000000000039726 · Cited by 1
Bliźniewska-Kowalska, K. M., Gałecki, P., Czarny, P. L., Szemraj, J., Kołodziej, Ł., & Gałecka, M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26178653 · Cited by 1
Approche pharmacogénétique de la réponse aux antipsychotiques chez les schizophrènes
Moulier, V., & Januel, D. (2007) · L Encéphale · doi:10.1016/j.encep.2007.01.004 · Cited by 1
Pharmacogenomics of Attention-Deficit/Hyperactivity Disorder
Froehlich, T. E., & Stein, M. A. (2010) · Advances in biological psychiatry · doi:10.1159/000317300 · Cited by 1
Atabay, M. M., Öz, Z. S., & Kurtman, E. (2014) · Molecular Biology Reports · doi:10.1007/s11033-014-3389-x · Cited by 1
Mallet, J. J., Laurent‐Levinson, C., Meloni, R., & Nosten‐Bertrand, M. (1996) · Annales de l Institut Pasteur / Actualités · doi:10.1016/0924-4204(96)82114-7 · Cited by 1
Genetic studies of bipolar disorder in patients selected by their treatment response
Ortiz‐Domínguez, A., & Alda, M. (2008) · Redalyc (Universidad Autónoma del Estado de México) · Cited by 1
Dopamine Receptor Diversity: Anatomy, Function, and Relevance to Parkinson’s Disease
Mash, D. C. (2003) · CRC Press eBooks · doi:10.1201/9780203912164-17 · Cited by 1
Genetikai hatások a korai kötődés fejlődésében
Gervai, J., Tóth, I., & Lakatos, K. (2017) · Magyar Pszichológiai Szemle · doi:10.1556/0016.2017.72.1.2 · Cited by 1
Amiri, S., Farhang, S., Khaniani, M. S., Derakhshan, S. M., Zadfattah, A., Bina, Z. M., Ghazipour, F., Sardari, N., Barzegar, H., & Fanid, L. M. (2021) · Journal of Comprehensive Pediatrics · doi:10.5812/compreped.109377 · Cited by 1
Chen, Z., & Fu, S. M. (2024) · European Journal of Neuroscience · doi:10.1111/ejn.16283 · Cited by 1
The extraordinary “ordinary magic” of resilience
Grigorenko, E. L. (2024) · Development and Psychopathology · doi:10.1017/s0954579424000841 · Cited by 3
A Multi-Gene by Environment Perspective of ADHD Symptomatology in Young Children
Allison, A. L. (2013) · ScholarWorks @ The University of New Orleans (The University of New Orleans) · Cited by 1
Candidate Gene Studies of Attention Deficit Hyperactivity Disorder
Güney, E., Ceylan, M. F., & İşeri, E. (2011) · Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry · doi:10.5455/cap.20110330 · Cited by 1
Pharmacogenomics in Psychiatric Disorders
Lam, Y. W. F., Fukui, N., Sugai, T., Watanabe, J., Watanabe, Y., Suzuki, Y., & Someya, T. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-391918-2.00006-8 · Cited by 1
Sensing Happiness in Senseless Information
Özdilek, Ü. (2020) · Applied Research in Quality of Life · doi:10.1007/s11482-020-09854-x · Cited by 1
Cities, Psychosis, and Social Defeat
Sayanvala, F., Bornstein, L., Choudhury, S., Shah, J. L., Weinstock, D., & Gold, I. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108695374.025 · Cited by 1
Culture, Mind, and Brain in Human Evolution
Stout, D. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108695374.005 · Cited by 1
Liminal Brains in Uncertain Futures
Choudhury, S., & Berson, J. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108695374.020 · Cited by 1
DRD4 Allele Frequency as a Lab Exercise in Neuroscience and Genetics Courses.
Koob, A. O., Ballantyne, S. M., Levesque, A. A., Qureshi, A. A., & Congdon, S. T. (2021) · PubMed · Cited by 1
Miller, E. M. (2014) · UKnowledge (University of Kentucky) · Cited by 1
Neuere Ergebnisse molekulargenetischer Untersuchungen bei psychotischen Erkrankungen
Körner, J., Nöthen, M. M., Rietschel, M., Möller, H.-J., & Propping, P. (1996) · Springer eBooks · doi:10.1007/978-3-7091-9414-0_8 · Cited by 1
Shalev, I., Lerer, E., Israel, S., Uzefovsky, F., Gritsenko, I., Mankuta, D., Kaitz, M., & Ebstein, R. P. (2009) · Wiley eBooks · doi:10.1002/9783527628346.ch6 · Cited by 1
Restrepo, J. E. (2013) · Gredos (University of Salamanca) · doi:10.14201/gredos.124205 · Cited by 1
Genetic architecture and behavioral analysis of attention and impulsivity
Loos, M. (2012) · Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) · Cited by 1
Catecol O-metiltransferase e o transtorno obsessivo-compulsivo: revisão sistemática com meta-análise
Sampaio, A. S. (2012) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.5.2012.tde-27112012-105200 · Cited by 2
Bakker, P. R. (2012) · Research Publications (Maastricht University) · doi:10.26481/dis.20120523pb · Cited by 1
Civelli, O., & Borrelli, E. (2010) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0000097.pub2 · Cited by 1
Self-citationMecânica estatística de sistemas de agentes bayesianos: aplicação à teoria dos fundamentos morais
Cesar, J. E. D. S. (2014) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.43.2014.tde-30102014-090629 · Cited by 1
Dr. Ekelund and Colleagues Reply
Ekelund, J., Lichtermann, D., & Peltonen, L. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.11.1885-a · Cited by 1
Shankar, P. (2003) · Dyuthi Digital Repository (Cochin University of Science and Technology) · Cited by 1
ADHD Pharmacogenomics: Past, Present, and Future
McGough, J. J., & Stein, M. A. (2007) · Medical psychiatry · doi:10.3109/9781420017144.033 · Cited by 1
Klinische Relevanz pharmakogenetischer Phänotypisierungen
Baumann, P., & Eap, C. B. (1993) · Springer eBooks · doi:10.1007/978-3-7091-9263-4_152 · Cited by 1
Untersuchungen zur genetischen Variabilität von Dopamin- und Serotonin-Rezeptoren
Nöthen, M. M., Erdmann, J., Cichon, S., Shimron‐Abarbanell, D., & Propping, P. (1996) · Springer eBooks · doi:10.1007/978-3-7091-6889-9_127 · Cited by 1
Ishiguro, H., Saito, T., Shibuya, H., & Arinami, T. (2000) · Alcoholism Clinical and Experimental Research · doi:10.1097/00000374-200003000-00015 · Cited by 1
Dopamine D4 Receptors: Molecular Biology and Pharmacology
Civelli, O. (2002) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-56051-4_8 · Cited by 1
Self-citationMolekulare Grundlagen der Interaktion zwischen Dopamin-(D1-/D2-)Rezeptoren
Niznik, H. B., Sunahara, R. K., Pristupa, Z. B., & Jarvie, K. R. (1995) · Springer eBooks · doi:10.1007/978-3-642-79738-5_1 · Cited by 1
Self-citationSchizophrenia Treatment Strategies
Meltzer, H. Y. (1996) · Humana Press eBooks · doi:10.1007/978-1-59259-466-5_1 · Cited by 1
Genetic Variation Analysis in Parkinson Disease Patients With and Without Hallucinations
Goetz, C. G., Burke, P. F., Leurgans, S. E., Berry‐Kravis, E., Blasucci, L. M., Raman, R., & Zhou, L. (2001) · Archives of Neurology · doi:10.1001/archneur.58.2.209
Vulnerability to cocaine : role of stress hormones
de Jong, I. J. (2007)
Comparative genomics of amino acid tandem repeats
Mularoni, L. (2009) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Ackenheil, M., & Weber, K. (2004) · Springer eBooks · doi:10.1007/978-3-7091-0623-5_16
Major depressive disorders: depressive disorders
Serretti, A., & Artioli, P. (2006) · Springer eBooks · doi:10.1007/0-387-34577-2_3
GENETIC LINKS TO THE REINFORCING EFFECTS OF ALCOHOL IN A SOCIAL CONTEXT
Creswell, K. G. (2012) · D-Scholarship@Pitt (University of Pittsburgh)
Dholkawala, F. S. (2014) · Human Biology
Candidate Gene Approaches to Schizophrenia
Kunugi, H. (2000) · International Journal of Mental Health · doi:10.1080/00207411.2000.11449496
Florijn, W. J., Tarazi, F. I., & Creese, I. (1997) · Principles of medical biology · doi:10.1016/s1569-2582(97)80066-9
Robinson, R., & Paulose, C. S. (2007) · Dyuthi Digital Repository (Cochin University of Science and Technology)
Ash, H. (2014) · Stirling Online Research Repository (University of Stirling)
Cognitive and biological individual differences in problematic alcohol use
Wildenberg, E. V. D. (2007) · Research Publications (Maastricht University) · doi:10.26481/dis.20070614ew
Villalba, K. (2014) · FIU - Digital Commons (Florida International University) · doi:10.25148/etd.fi14110727
Behavioral impulsivity and hallucinations : insights from Parkinson's disease
Ashourian, P. (2011) · DSpace@MIT (Massachusetts Institute of Technology)
Novel antipsychotics with unique D2/5-HT1A affinity and minimal extrapyramidal side effect liability
Reitz, A. B., & Scott, M. K. (1995) · Advances in medicinal chemistry · doi:10.1016/s1067-5698(06)80003-9
Lobo, D. S. S. (2005) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.5.2005.tde-02092005-150159
Sheikh, H. I. (2014) · Scholarship@Western (Western University)
Die Rolle der Pharmakogenetik/-genomic für die Behandlung der Schizophrenie
Ackenheil, M. (2006) · Springer eBooks · doi:10.1007/3-211-29109-1_9
Assessment of Pharmacokinetics and Pharmacodynamics of Psychoactive Drugs using Brain Microdialysis
Sood, P. (2010) · Figshare
Multiple Dopamine Receptors: Implications for Schizophrenia
Sokoloff, P., Martres, M., Lévesque, D., Díaz, J., Pilon, C., Griffon, N., & Schwartz, J. (1995) · Springer eBooks · doi:10.1007/978-3-642-79429-2_12
Gardner, W. O. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.11.1884-b
Paul, J. (2011) · Dyuthi Digital Repository (Cochin University of Science and Technology)
Ahn, R. (2012) · Scholarship - Claremont (Claremont Colleges)
Williams, Y. S. (2011) · UKnowledge (University of Kentucky)
GENETICS OF MAJOR DEPRESSIVE DISORDER IN TREATMENT RESISTANCE AND TRYPTOPHAN DEPLETION
Garriock, H. A. (2006) · UA Campus Repository (The University of Arizona)
XXVI-7 Neurogenetics of Personality Disorders
Reif, A., & Lesch, K. (2002)
Marques, F. Z. (2006) · Americanae (AECID Library)
Polymorphic Variation at Neurotransmitter Receptor Loci and Clinical Response
Adityanjee, & Jampala, V. C. (1996) · Psychiatric Annals · doi:10.3928/0048-5713-19960701-09
Patte, K. A. (2015) · YorkSpace (York University)
Personality Genetics and Health in Super-Seniors
Nelson, J. M. T. (2015) · Summit (Simon Fraser University)
Dopamine D2 Receptor Functional Selectivity as a Mechanism of Atypical Antipsychotic Drug Action
Urban, J. D. (2006) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/q8t3-p159 · Cited by 1
Giardino, E. (2015) · Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) · doi:10.13130/giardino-elena_phd2015-12-17
Evolution of Neurotransmitter-Related Genes in Primates
Inoue‐Murayama, M., Niimi, Y., ADACHI, S., MITANI, H., Takenaka, O., Ito, S., & Murayama, Y. (2000) · Primate Research · doi:10.2354/psj.16.69
Sasaki, T., & Kennedy, J. L. (1995) · Current Opinion in Psychiatry · doi:10.1097/00001504-199501000-00007
Self-citationGüney, E., & Ceylan, M. F. (2011)
Sugamori, K. S., Sunahara, R. K., Guan, H., BULLOCHt, A. G. M., Seeman, P. M., Niznik, H. B., & Tol, H. H. M. V. (2016)
Self-citationBiochemistry and Molecular Biology Techniques
Herrero, S., & Ivorra, J. L. (2008)
New Perspectives on the Clinical Neurobiology of Treatment Response in Schizophrenia
Honer, W. G. (1994) · The Canadian Journal of Psychiatry · doi:10.1177/070674379403900108
Genetic Disorders of the Autonomic Nervous System
Peroutka, S. J. (2007) · Elsevier eBooks · doi:10.1016/b978-012369509-3.50023-8
Knockout Mice in the Study of Dopaminergic Diseases
Aoyama, S., Kase, H., Baik, J., & Borrelli, E. (2000) · Elsevier eBooks · doi:10.1016/b978-012400405-4/50010-1
Analysis of dopamine receptor and dopamine transporter genes in schizophrenia
Yamaguchi, K. (1996) · Okayama Igakkai Zasshi (Journal of Okayama Medical Association) · doi:10.4044/joma1947.108.7-8_253
Kanazawa, I. (1992) · Internal Medicine · doi:10.2169/internalmedicine.31.1411
Add Health Wave IV Documentation Report
Whitsel, E. A., Cuthbertson, C. C., Tabor, J. W., Potter, A., Wener, M. H., Clapshaw, P. A., Killeya‐Jones, L. A., Halpern, C. T., & Harris, K. M. (2013)
A study on candidate gene polymorphisms in association with mental retardation
Bhowmik, A. D. (2010) · Shodhganga
Variation of the pseudogene for a serotonin-7-like receptor
Nam, D. (1997) · Library and Archives Canada (Government of Canada)
Az impulzivitás genetikai korrelátumai
Varga, G. (2015) · Eötvös Loránd Tudományegyetem · doi:10.15476/elte.2014.096
Metadata
- Authors
- Tol, H. H. M. V., Wu, C. M., Guan, H.-C., Ohara, K., Bunzow, J. R., Civelli, O., Kennedy, J., Seeman, P., Niznik, H. B., & Jovanovic, V.
- Affiliations
- University of Toronto (CA)
- Oregon Health & Science University (US)
- Venue
- Nature
- Published
- 1992-07
- Volume
- 358
- Issue
- 6382
- Pages
- 149-152
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2026395566
- Cited by
- 955
- References
- 20
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 10 · 2023: 15 · 2022: 10 · 2021: 14 · 2020: 43 · 2019: 15 · 2018: 7 · 2017: 12 · 2016: 32 · 2015: 34 · 2014: 26 · 2013: 23 · 2012: 35
- FWCI
- 16.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- dopamine D4 receptor, genetic polymorphism, receptor isoforms, spiperone binding, direct repeats, cytoplasmic loop, atypical antipsychotics, individual differences in drug response
- MeSH terms
- Base Sequence, Binding, Competitive, Cell Line, Clozapine, DNA, DNA Restriction Enzymes, Humans, Introns, Molecular Sequence Data, Pituitary Gland, Receptors, Dopamine, Repetitive Sequences, Nucleic Acid, Spiperone, Substantia Nigra, Transfection, Genetic Variation, Gene Expression, Receptors, Dopamine D2, Receptors, Dopamine D4
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review