Identification and characterization of a novel serine-threonine kinase gene from the Xp22 region.
Eukaryotic protein kinases are part of a large and expanding family of proteins. Through our transcriptional mapping effort in the Xp22 region, we have isolated and sequenced the full-length transcript of STK9, a novel cDNA highly homologous to serine-threonine kinases. A number of human genetic disorders have been mapped to the region where STK9 has been localized including Nance-Horan (NH) syndrome, oral-facial-digital syndrome type 1 (OFD1), and a novel locus for nonsyndromic sensorineural deafness (DFN6). To evaluate the possible involvement of STK9 in any of the above-mentioned disorders, a 2416-bp full-length cDNA was assembled. The entire genomic structure of the gene, which is composed of 20 coding exons, was determined. Northern analysis revealed a transcript larger than 9.5 kb in several tissues including brain, lung, and kidney. The mouse homologue (Stk9) was identified and mapped in the mouse in the region syntenic to human Xp. This location is compatible with the location of the Xcat mutant, which shows congenital cataracts very similar to those observed in NH patients. Sequence homologies, expression pattern, and mapping information in both human and mouse make STK9 a candidate gene for the above-mentioned disorders.
Telethon Institute of Genetics and Medicine (TIGEM), San Raffaele Biomedical Science Park, Milan, Italy.
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E
Montini
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G
Andolfi
A
A
Caruso
G
G
Buchner
S M
SM
Walpole
M
M
Mariani
G
G
Consalez
D
D
Trump
A
A
Ballabio
B
B
Franco
D000595:Amino Acid Sequence; D000818:Animals; D016203:CDC2 Protein Kinase / Q000737:chemistry; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018844:Cyclin-Dependent Kinases; D030342:Genetic Diseases, Inborn / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry*; D012326:RNA Splicing / Q000235:genetics; D015183:Restriction Mapping; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014960:X Chromosome / Q000235:genetics*
D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D016203:CDC2 Protein Kinase; C096702:CDKL1 protein, human; C103570:CDKL2 protein, human; C114482:CDKL5 protein, human; C521371:Cdkl2 protein, mouse; D018844:Cyclin-Dependent Kinases