Susumu Mitsuyama

The KMDB/MutationView: a mutation database for human disease genes

The KMDB/MutationView is a graphical database of mutations in human disease-causing genes and its current version consists of nine category-based sub-databases including diseases of eye, heart, ear, brain, cancer, syndrome, autoimmunity, muscle and blood. The KMDB/MutationView stores mutation data of 97 genes involved in 87 different disease and is accessible through http://mutview.dmb.med. keio.ac.jp.

Eye disorder database "KMeyeDB".

The KMeyeDB (http://mutview.dmb.med.keio.ac.jp) has been developed as a database of mutations in human eye disorder genes using software called MutationView which provides graphical presentation of various data analysis. Here, we present several display windows from the KMeyeDB for data analysis of mutations in the RB‐1 gene, which is responsible for the pathogenesis of retinoblastoma, a malignant tumor in the retina. Hum Mutat 15:95–98, 2000.

Keio Mutation Database for eye disease genes (KMeyeDB)

A database of mutations in human eye disease genes has been constructed. This KMeyeDB employs a database software MutationView which provides graphical data presentation and analysis as a smooth user-interface. Currently, the KMeyeDB contains mutation data of 16 different genes for 18 eye diseases. The KMeyeDB is accessible through http://mutview.dmb.med.keio.ac.jp with advanced internet browsers.

KMeyeDB: a graphical database of mutations in genes that cause eye diseases.

KMeyeDB (http://mutview.dmb.med.keio.ac.jp/) is a database of human gene mutations that cause eye diseases. We have substantially enriched the amount of data in the database, which now contains information about the mutations of 167 human genes causing eye‐related diseases including retinitis pigmentosa, cone‐rod dystrophy, night blindness, Oguchi disease, Stargardt disease, macular degeneration, Leber congenital amaurosis, corneal dystrophy, cataract, glaucoma, retinoblastoma, Bardet–Biedl syndrome, and Usher syndrome. KMeyeDB is operated using the database software MutationView, which deals with various characters of mutations, gene structure, protein functional domains, and polymerase chain reaction (PCR) primers, as well as clinical data for each case. Users can access the database using an ordinary Internet browser with smooth user‐interface, without user registration. The results are displayed on the graphical windows together with statistical calculations. All mutations and associated data have been collected from published articles. Careful data analysis with KMeyeDB revealed many interesting features regarding the mutations in 167 genes that cause 326 different types of eye diseases. Some genes are involved in multiple types of eye diseases, whereas several eye diseases are caused by different mutations in one gene. Hum Mutat 31:1–8, 2010.

Keio Mutation Database (KMDB) for human disease gene mutations

A database of mutations in human disease-causing genes has been constructed and named as Keio Mutation Database (KMDB). This KMDB utilizes a database software called MutationView which was designed to compile various mutation data and to provide graphical presentation of data analysis. Currently, the KMDB accommodates mutation data of 38 different genes for 35 different diseases which are involved in eye, heart, ear and brain. These KMDBs are accessible through http://mutview.dmb.med.keio.ac.jp with advanced internet browsers.

The KM-parkin-DB: A Sub-set MutationView Database Specialized for PARK2 (PARKIN) Variants

We previously isolated PARKIN (PARK2) as a gene responsible for a unique sort of Parkinson disease, namely Autosomal Recessive Juvenile Parkinsonism (ARJP). In this study, we surveyed all the available literature describing PARK2 gene/Parkin protein mutations found in Parkinson disease patients. Only carefully evaluated data were deposited in the graphical database MutationView (http://mutview.dmb.med.keio.ac.jp) to construct KM‐parkin‐DB, an independent sub‐set database. Forty‐four articles were selected for data curation regarding clinical information such as ethnic origins, manifested symptoms, onset age, and hereditary patterns as well as mutation details including base changes and zygosity. A total of 366 cases were collected from 39 ethnic origins and 96 pathogenic mutations were found. PARK2 gene mutations were found also in some general Parkinson disease patients. The majority (63%) of mutations in PARK2 were restricted to two particular domains (UBL and RING1) of the Parkin protein. In these domains, two major mutations, a large deletion (DelEx3) and a point mutation (p.Arg275Trp), were located.

Novel Bernard-Soulier syndrome variants caused by compound heterozygous mutations (case I) or a cytoplasmic tail truncation (case II) of GPIbα

A defective platelet glycoprotein (GP) Ib/IX/V complex [von Willebrand factor (VWF) receptor] results in Bernard-Soulier syndrome (BSS), which is characterized by macrothrombocytopenia and impaired ristocetin- and thrombin-induced platelet aggregation. We found 2 independent BSS-variant families: Case I [compound heterozygous mutations, p.Glu331X and a frame shift by a deletion at c.1444delA of GPIbα (GP1BA) terminating at a premature stop codon (p.Thr452ProfsX58)], and case II [homozygous nonsense mutation at c.1723C>T, p.Gln545X]. Case I platelets expressed no GPIbα, resulting in absence of ristocetin-induced platelet aggregation (RIPA) and 50% reduction in thrombin-induced aggregation with no shape change. The mothers platelets had 50% the expression level of A-type GPIbα (4-repeated VNTR: variable number of tandem repeats, p.[Thr145Met; Ser399_Pro411[4]]); the fathers platelets had the same expression level of C-type GPIbα (2-repeated VNTR, p.Ser399_Pro411dup) as the mothers platelets. The mothers RIPA was significantly higher than the fathers. Thrombin-induced aggregation was normal in both parents. Case II platelets expressed a GPIbα with an abnormal cytoplasmic tail, p.Gln545X-truncated GPIbα, which complexed with GPIX and GPV on the cell surface; its expression level of the complex was normal. Case II platelets had reversible RIPA, with no ATP release, and weak thrombin-induced aggregation without shape change. These results suggest that a signaling process through the GPIbα cytoplasmic tail required for full platelet activation is defective in BSS variant case II and a length polymorphism of GPIbα is associated with a modified level of RIPA heterozygous BSS case I.

CancerProView: a graphical image database of cancer-related genes and proteins.

We have developed a graphical image database CancerProView (URL: http://cancerproview.dmb.med.keio.ac.jp/php/cpv.html) to assist the search for alterations of the motifs/domains in the cancer-related proteins that are caused by mutations in the corresponding genes. For the CancerProView, we have collected various kinds of data on 180 cancer-related proteins in terms of the motifs/domains, genomic structures of corresponding genes, and 109 charts of the protein interaction pathways. Moreover, we have collected the relevant data on 1041 reference genes including 197 non-cancer disease-associated genes, and the nucleotide sequences for 2011 full-length cDNAs and the alternatively spliced transcript variants. Thus, the CancerProView database system would provide valuable information to facilitate basic cancer research as well as for designing new molecular diagnosis and drug discovery for cancers. The CancerProView database can be operated via Internet with any Web browser, and the system is freely available to interested users without ID and password.