PMC:2812425 / 11378-13700
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/2812425","sourcedb":"PMC","sourceid":"2812425","source_url":"https://www.ncbi.nlm.nih.gov/pmc/2812425","text":"Previous studies on HGF suggest a function of the GINGF3 gene product in cell cycle control, and more specifically, the gene product might directly or indirectly interact with SOS1. A heterozygous SOS1 single base insertion leading to a C-terminally truncated protein, leading to sustained activation of RAS/MAPK signaling in fibroblasts, was identified in the form of HGF [12, 13]. Mutations in another component of the RAS/MAPK pathway, HRAS, can cause Costello syndrome, a malformation-dysmorphism syndrome with gingival hypertrophy as a feature [14]. Most recently, dysregulation of the human mitogen-activated protein kinase kinase 6 (MAP2K6) was implicated in the pathogenesis of a syndromic form of HGF, congenital generalized hypertrichosis terminalis [15]. Therefore, genes from the candidate region encoding for components of the RAS/MAPK pathway will be given priority regarding sequence analysis to identify the mutation causing HGF in the presented family. For example, RAB10 from the interval encodes a member of the RAS (see HRAS; OMIM 190020) superfamily of small GTPases. RAB proteins localize to exocytic and endocytic compartments and regulate intracellular vesicle trafficking; however, the particular function of RAB10 is unknown. Most genes from the candidate region are incompletely characterized such as GPN1, which encodes a guanosine triphosphatase enzyme that may play a role in DNA repair and may function in activation of transcription, and AGBL5, a putative ATP/GTP binding protein. CIB4, encoding calcium and integrin binding family member 4, may represent a further HGF candidate gene considering that calcium channel blockers can induce gingival hyperplasia. Candidates further include PPP1CB, encoding one of the three catalytic subunits of protein phosphatase 1, which is known to be involved in the regulation of cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription, and the protein encoded by FKBP1B, a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. FKBP1B is a cis-trans prolyl isomerase that binds the immunosuppressant FK506 (Tacrolimus), which can induce gingival overgrowth as a side-effect in treated patients [16, 17].","tracks":[{"project":"MyTest","denotations":[{"id":"19633868-11868160-29215970","span":{"begin":374,"end":376},"obj":"11868160"},{"id":"19633868-17510059-29215971","span":{"begin":378,"end":380},"obj":"17510059"},{"id":"19633868-17726614-29215972","span":{"begin":550,"end":552},"obj":"17726614"},{"id":"19633868-19463983-29215973","span":{"begin":761,"end":763},"obj":"19463983"},{"id":"19633868-15016038-29215974","span":{"begin":2314,"end":2316},"obj":"15016038"},{"id":"19633868-18589122-29215975","span":{"begin":2318,"end":2320},"obj":"18589122"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"attributes":[{"subj":"19633868-11868160-29215970","pred":"source","obj":"MyTest"},{"subj":"19633868-17510059-29215971","pred":"source","obj":"MyTest"},{"subj":"19633868-17726614-29215972","pred":"source","obj":"MyTest"},{"subj":"19633868-19463983-29215973","pred":"source","obj":"MyTest"},{"subj":"19633868-15016038-29215974","pred":"source","obj":"MyTest"},{"subj":"19633868-18589122-29215975","pred":"source","obj":"MyTest"}]},{"project":"2_test","denotations":[{"id":"19633868-11868160-29215970","span":{"begin":374,"end":376},"obj":"11868160"},{"id":"19633868-17510059-29215971","span":{"begin":378,"end":380},"obj":"17510059"},{"id":"19633868-17726614-29215972","span":{"begin":550,"end":552},"obj":"17726614"},{"id":"19633868-19463983-29215973","span":{"begin":761,"end":763},"obj":"19463983"},{"id":"19633868-15016038-29215974","span":{"begin":2314,"end":2316},"obj":"15016038"},{"id":"19633868-18589122-29215975","span":{"begin":2318,"end":2320},"obj":"18589122"}],"attributes":[{"subj":"19633868-11868160-29215970","pred":"source","obj":"2_test"},{"subj":"19633868-17510059-29215971","pred":"source","obj":"2_test"},{"subj":"19633868-17726614-29215972","pred":"source","obj":"2_test"},{"subj":"19633868-19463983-29215973","pred":"source","obj":"2_test"},{"subj":"19633868-15016038-29215974","pred":"source","obj":"2_test"},{"subj":"19633868-18589122-29215975","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"MyTest","color":"#ecde93","default":true},{"id":"2_test","color":"#c493ec"}]}]}}