DISC1

From Wikipedia, the free encyclopedia

Disrupted in schizophrenia 1

Identifiers

DISC1; SCZD9; KIAA0457

External IDs

OMIM: 605210 MGI: 2447658 HomoloGene: 10257

Gene ontology
Molecular Function:	• protein binding
Cellular Component:	• cellular_component • cytoskeleton • microtubule
Biological Process:	• biological_process

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

n/a

n/a

Refseq

NM_001012957 (mRNA)
NP_001012975 (protein)

NM_170596 (mRNA)
NP_733484 (protein)

Location

Chr 1: 229.83 - 230.24 Mb

n/a

Pubmed search

[1]

[2]

Disrupted in Schizophrenia 1 or DISC1 is a protein with a wide array of interactions. It participates in cell growth, movement, axonal growth and transport, neural positioning. Among its known partners are LIS1 and NUDEL proteins and PDE4B enzyme. Disruptions in DISC1 structure may play an important role at least in some cases of schizophrenia, however the evidence from genetic linkage and association studies suggests that variants of DISC1 do not play a significant role in most cases of schizophrenia, although DISC1 may be more important in bipolar disorder.

This gene encodes a protein with multiple coiled coil motifs which is located in the nucleus, cytoplasm and mitochondria. The protein is involved in neurite outgrowth and cortical development through its interaction with other proteins. This gene is disrupted in a t(1;11)(q42.1;q14.3) translocation which segregates with schizophrenia and related psychiatric disorders in a large Scottish family. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.^[1]

[edit] References

^ Entrez Gene: DISC1 disrupted in schizophrenia 1.

[edit] Further reading

Blackwood DH, Muir WJ (2004). "Clinical phenotypes associated with DISC1, a candidate gene for schizophrenia.". Neurotoxicity research 6 (1): 35-41. PMID 15184103.
Millar JK, James R, Brandon NJ, Thomson PA (2005). "DISC1 and DISC2: discovering and dissecting molecular mechanisms underlying psychiatric illness.". Ann. Med. 36 (5): 367-78. PMID 15478311.
Porteous DJ, Thomson P, Brandon NJ, Millar JK (2006). "The genetics and biology of DISC1--an emerging role in psychosis and cognition.". Biol. Psychiatry 60 (2): 123-31. doi:10.1016/j.biopsych.2006.04.008. PMID 16843095.
Lipska BK, Mitkus SN, Mathew SV, et al. (2006). "Functional genomics in postmortem human brain: abnormalities in a DISC1 molecular pathway in schizophrenia.". Dialogues in clinical neuroscience 8 (3): 353-7. PMID 17117617.
Seki N, Ohira M, Nagase T, et al. (1998). "Characterization of cDNA clones in size-fractionated cDNA libraries from human brain.". DNA Res. 4 (5): 345-9. PMID 9455484.
Millar JK, Wilson-Annan JC, Anderson S, et al. (2000). "Disruption of two novel genes by a translocation co-segregating with schizophrenia.". Hum. Mol. Genet. 9 (9): 1415-23. PMID 10814723.
Millar JK, Christie S, Semple CA, Porteous DJ (2001). "Chromosomal location and genomic structure of the human translin-associated factor X gene (TRAX; TSNAX) revealed by intergenic splicing to DISC1, a gene disrupted by a translocation segregating with schizophrenia.". Genomics 67 (1): 69-77. doi:10.1006/geno.2000.6239. PMID 10945471.
Blackwood DH, Fordyce A, Walker MT, et al. (2001). "Schizophrenia and affective disorders--cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family.". Am. J. Hum. Genet. 69 (2): 428-33. PMID 11443544.
Ekelund J, Hovatta I, Parker A, et al. (2001). "Chromosome 1 loci in Finnish schizophrenia families.". Hum. Mol. Genet. 10 (15): 1611-7. PMID 11468279.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899-903. doi:10.1073/pnas.242603899. PMID 12477932.
Ozeki Y, Tomoda T, Kleiderlein J, et al. (2003). "Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth.". Proc. Natl. Acad. Sci. U.S.A. 100 (1): 289-94. doi:10.1073/pnas.0136913100. PMID 12506198.
Taylor MS, Devon RS, Millar JK, Porteous DJ (2003). "Evolutionary constraints on the Disrupted in Schizophrenia locus.". Genomics 81 (1): 67-77. PMID 12573262.
Morris JA, Kandpal G, Ma L, Austin CP (2004). "DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation.". Hum. Mol. Genet. 12 (13): 1591-608. PMID 12812986.
Miyoshi K, Honda A, Baba K, et al. (2004). "Disrupted-In-Schizophrenia 1, a candidate gene for schizophrenia, participates in neurite outgrowth.". Mol. Psychiatry 8 (7): 685-94. doi:10.1038/sj.mp.4001352. PMID 12874605.
Hennah W, Varilo T, Kestilä M, et al. (2004). "Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects.". Hum. Mol. Genet. 12 (23): 3151-9. doi:10.1093/hmg/ddg341. PMID 14532331.
Millar JK, Christie S, Porteous DJ (2004). "Yeast two-hybrid screens implicate DISC1 in brain development and function.". Biochem. Biophys. Res. Commun. 311 (4): 1019-25. PMID 14623284.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40-5. doi:10.1038/ng1285. PMID 14702039.
Brandon NJ, Handford EJ, Schurov I, et al. (2004). "Disrupted in Schizophrenia 1 and Nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disorders.". Mol. Cell. Neurosci. 25 (1): 42-55. doi:10.1016/j.mcn.2003.09.009. PMID 14962739.
Miyoshi K, Asanuma M, Miyazaki I, et al. (2004). "DISC1 localizes to the centrosome by binding to kendrin.". Biochem. Biophys. Res. Commun. 317 (4): 1195-9. doi:10.1016/j.bbrc.2004.03.163. PMID 15094396.
James R, Adams RR, Christie S, et al. (2004). "Disrupted in Schizophrenia 1 (DISC1) is a multicompartmentalized protein that predominantly localizes to mitochondria.". Mol. Cell. Neurosci. 26 (1): 112-22. doi:10.1016/j.mcn.2004.01.013. PMID 15121183.