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Schizophrenia 3(SCZD3)

MedGen UID:
Concept ID:
Mental or Behavioral Dysfunction
Monarch Initiative: MONDO:0010897
OMIM®: 600511


A schizophrenia that has material basis in an autosomal dominant mutation of SCZD3 on chromosome 6p23. [from MONDO]

Clinical features

From HPO
MedGen UID:
Concept ID:
Mental or Behavioral Dysfunction
Schizophrenia is highly heritable, as shown by family, twin, and adoption studies. For example, for identical twins, if one twin develops schizophrenia, the other twin has about a 50% chance of also developing the disease. The risk of the general population developing the schizophrenia is about 0.3-0.7% worldwide. The search for “schizophrenia genes” has been elusive. Initial linkage studies looked at parts of the genome associated with schizophrenia, and many candidate genes were identified, including APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GRIN2B, HP, IL1B, MTHFR, PLXNA2, SLC6A4, TP53, and TPH1. However, some of these have later been questioned. Microdeletions and microduplications have been found to be three times more common in individuals with schizophrenia, compared to controls. Because these deletions and duplications are in genes that are overexpressed in pathways related to brain development, it is possible that the inheritance of multiple rare variants may contribute to the development of schizophrenia. Several genetic disorders feature schizophrenia as a clinical feature. The 22q11.2 Deletion Syndrome comprises many different syndromes, of which one of the most serious is DiGeorge syndrome. Children born with DiGeorge syndrome typically have heart defects, cleft palate, learning difficulties, and immune deficiency. Schizophrenia is a late manifestation, affecting around 30% of individuals. Microdeletions and duplications in chromosome 1, 2, 3, 7, 15 and 16 have also been associated with schizophrenia. In 2014, a genome-wide association study looked at the genomes of over 35,000 patients and 110,00 controls. The study identified 108 SNPs that were associated with schizophrenia, 83 of which had not been previously reported. As expected, many of these loci occurred in genes that are expressed in the brain. For example, the SNPs included a gene that encodes the dopamine D2 receptor, DRD2 (the target of antipsychotic drugs), and many genes involved in glutamine neurotransmitter pathways and synaptic plasticity (e.g., GRM3, GRIN2A, SRR, GRIA1). More surprisingly, however, associations were also enriched among genes expressed in tissues with important immune functions. In 2016, a study based on nearly 65,000 people investigated the association between schizophrenia and variation in the Major Histocompatibility Complex (MHC) locus—a region on chromosome 6 that is important for immune function. The study focused on the C4 gene (complement component 4) that exists as two distinct genes: C4A and C4B, which encode particularly structurally diverse alleles. The study found that the alleles which promoted greater expression of C4A in the brain were associated with a greater risk of schizophrenia. By using mice models, the study showed that C4 is involved in the elimination of synapses during brain maturation. In humans, “synaptic pruning” is most active during late adolescence, which coincides with the typical onset of symptoms of schizophrenia. It is therefore possible that the inheritance of specific C4A alleles could lead to “run away” synaptic pruning, increasing the risk of schizophrenia. Further research may even determine C4 as a potential therapeutic target.
Abnormality of the nervous system
MedGen UID:
Concept ID:
Congenital Abnormality
An abnormality of the nervous system.

Professional guidelines


Panizzutti B, Skvarc D, Lin S, Croce S, Meehan A, Bortolasci CC, Marx W, Walker AJ, Hasebe K, Kavanagh BE, Morris MJ, Mohebbi M, Turner A, Gray L, Berk L, Walder K, Berk M, Dean OM
Int J Mol Sci 2023 Mar 9;24(6) doi: 10.3390/ijms24065250. PMID: 36982324Free PMC Article
Kane JM, McEvoy JP, Correll CU, Llorca PM
CNS Drugs 2021 Nov;35(11):1189-1205. Epub 2021 Oct 11 doi: 10.1007/s40263-021-00861-6. PMID: 34636025Free PMC Article
Smolak A, Gearing RE, Alonzo D, Baldwin S, Harmon S, McHugh K
Community Ment Health J 2013 Aug;49(4):444-50. Epub 2012 Aug 2 doi: 10.1007/s10597-012-9536-8. PMID: 22855264Free PMC Article

Recent clinical studies


Laverty D, Desai R, Uchański T, Masiulis S, Stec WJ, Malinauskas T, Zivanov J, Pardon E, Steyaert J, Miller KW, Aricescu AR
Nature 2019 Jan;565(7740):516-520. Epub 2019 Jan 2 doi: 10.1038/s41586-018-0833-4. PMID: 30602789Free PMC Article
Julie G, Hamdan FF, Rouleau GA
J Vis Exp 2011 Jun 15;(52) doi: 10.3791/2534. PMID: 21712793Free PMC Article


Julie G, Hamdan FF, Rouleau GA
J Vis Exp 2011 Jun 15;(52) doi: 10.3791/2534. PMID: 21712793Free PMC Article

Clinical prediction guides

Julie G, Hamdan FF, Rouleau GA
J Vis Exp 2011 Jun 15;(52) doi: 10.3791/2534. PMID: 21712793Free PMC Article
Austin J, Hoogendoorn B, Buckland P, Speight G, Cardno A, Bowen T, Williams N, Spurlock G, Sanders R, Jones L, Murphy K, McCarthy G, McGuffin P, Owen MJ, O'Donovan MC
Mol Psychiatry 2000 Mar;5(2):208-12. doi: 10.1038/sj.mp.4000693. PMID: 10822351

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