Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico Analysis
FAM20C (family with sequence similarity 20, member C) is a serine/threonine-specific protein kinase that is ubiquitously expressed and mainly associated with biomineralization and phosphatemia regulation. It is mostly known due to pathogenic variants causing its deficiency, which results in Raine sy...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/10/8904 |
| _version_ | 1797599774317215744 |
|---|---|
| author | Icela Palma-Lara Patricia García Alonso-Themann Javier Pérez-Durán Ricardo Godínez-Aguilar José Bonilla-Delgado Damián Gómez-Archila Ana María Espinosa-García Manuel Nolasco-Quiroga Georgina Victoria-Acosta Adolfo López-Ornelas Juan Carlos Serrano-Bello María Guadalupe Olguín-García Carmen Palacios-Reyes |
| author_facet | Icela Palma-Lara Patricia García Alonso-Themann Javier Pérez-Durán Ricardo Godínez-Aguilar José Bonilla-Delgado Damián Gómez-Archila Ana María Espinosa-García Manuel Nolasco-Quiroga Georgina Victoria-Acosta Adolfo López-Ornelas Juan Carlos Serrano-Bello María Guadalupe Olguín-García Carmen Palacios-Reyes |
| author_sort | Icela Palma-Lara |
| collection | DOAJ |
| description | FAM20C (family with sequence similarity 20, member C) is a serine/threonine-specific protein kinase that is ubiquitously expressed and mainly associated with biomineralization and phosphatemia regulation. It is mostly known due to pathogenic variants causing its deficiency, which results in Raine syndrome (RNS), a sclerosing bone dysplasia with hypophosphatemia. The phenotype is recognized by the skeletal features, which are related to hypophosphorylation of different FAM20C bone-target proteins. However, FAM20C has many targets, including brain proteins and the cerebrospinal fluid phosphoproteome. Individuals with RNS can have developmental delay, intellectual disability, seizures, and structural brain defects, but little is known about FAM20C brain-target-protein dysregulation or about a potential pathogenesis associated with neurologic features. In order to identify the potential FAM20C actions on the brain, an in silico analysis was conducted. Structural and functional defects reported in RNS were described; FAM20C targets and interactors were identified, including their brain expression. Gene ontology of molecular processes, function, and components was completed for these targets, as well as for potential involved signaling pathways and diseases. The BioGRID and Human Protein Atlas databases, the Gorilla tool, and the PANTHER and DisGeNET databases were used. Results show that genes with high expression in the brain are involved in cholesterol and lipoprotein processes, plus axo-dendritic transport and the neuron part. These results could highlight some proteins involved in the neurologic pathogenesis of RNS. |
| first_indexed | 2024-03-11T03:40:06Z |
| format | Article |
| id | doaj.art-eba2982e36614d36874a50ae95db9375 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:40:06Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-eba2982e36614d36874a50ae95db93752023-11-18T01:43:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410890410.3390/ijms24108904Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico AnalysisIcela Palma-Lara0Patricia García Alonso-Themann1Javier Pérez-Durán2Ricardo Godínez-Aguilar3José Bonilla-Delgado4Damián Gómez-Archila5Ana María Espinosa-García6Manuel Nolasco-Quiroga7Georgina Victoria-Acosta8Adolfo López-Ornelas9Juan Carlos Serrano-Bello10María Guadalupe Olguín-García11Carmen Palacios-Reyes12Laboratorio de Morfología Celular y Molecular, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, MexicoInstituto Nacional de Perinatología Isidro Espinosa de los Reyes, Ciudad de México 11000, MexicoInstituto Nacional de Perinatología Isidro Espinosa de los Reyes, Ciudad de México 11000, MexicoDivisión de Investigación, Hospital Juárez de México, Ciudad de México 11340, MexicoUnidad de Investigación, Hospital Regional de Ixtapaluca, Ixtapaluca 56530, MexicoDepartamento de Oncología Quirúrgica, Hospital de Gineco-Obstetricia 3, Centro Médico Nacional “La Raza”, Ciudad de México 02990, MexicoLaboratorio de Farmacología Clínica, Hospital General de México, Ciudad de México 06720, MexicoCoordinación de Enseñanza e Investigación, Clínica Hospital Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Huauchinango 73177, MexicoDivisión de Investigación, Hospital Juárez de México, Ciudad de México 11340, MexicoDivisión de Investigación, Hospital Juárez de México, Ciudad de México 11340, MexicoDepartamento de Patología Clínica y Experimental, Hospital Infantil de México Federico Gómez, Ciudad de México 06720, MexicoCentro Dermatológico “Dr. Ladislao de la Pascua”, Ciudad de México 06780, MexicoDivisión de Investigación, Hospital Juárez de México, Ciudad de México 11340, MexicoFAM20C (family with sequence similarity 20, member C) is a serine/threonine-specific protein kinase that is ubiquitously expressed and mainly associated with biomineralization and phosphatemia regulation. It is mostly known due to pathogenic variants causing its deficiency, which results in Raine syndrome (RNS), a sclerosing bone dysplasia with hypophosphatemia. The phenotype is recognized by the skeletal features, which are related to hypophosphorylation of different FAM20C bone-target proteins. However, FAM20C has many targets, including brain proteins and the cerebrospinal fluid phosphoproteome. Individuals with RNS can have developmental delay, intellectual disability, seizures, and structural brain defects, but little is known about FAM20C brain-target-protein dysregulation or about a potential pathogenesis associated with neurologic features. In order to identify the potential FAM20C actions on the brain, an in silico analysis was conducted. Structural and functional defects reported in RNS were described; FAM20C targets and interactors were identified, including their brain expression. Gene ontology of molecular processes, function, and components was completed for these targets, as well as for potential involved signaling pathways and diseases. The BioGRID and Human Protein Atlas databases, the Gorilla tool, and the PANTHER and DisGeNET databases were used. Results show that genes with high expression in the brain are involved in cholesterol and lipoprotein processes, plus axo-dendritic transport and the neuron part. These results could highlight some proteins involved in the neurologic pathogenesis of RNS.https://www.mdpi.com/1422-0067/24/10/8904FAM20CRaine syndromebrain defectsin silico analysisgene ontologypathways |
| spellingShingle | Icela Palma-Lara Patricia García Alonso-Themann Javier Pérez-Durán Ricardo Godínez-Aguilar José Bonilla-Delgado Damián Gómez-Archila Ana María Espinosa-García Manuel Nolasco-Quiroga Georgina Victoria-Acosta Adolfo López-Ornelas Juan Carlos Serrano-Bello María Guadalupe Olguín-García Carmen Palacios-Reyes Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico Analysis International Journal of Molecular Sciences FAM20C Raine syndrome brain defects in silico analysis gene ontology pathways |
| title | Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico Analysis |
| title_full | Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico Analysis |
| title_fullStr | Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico Analysis |
| title_full_unstemmed | Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico Analysis |
| title_short | Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico Analysis |
| title_sort | potential role of protein kinase fam20c on the brain in raine syndrome an in silico analysis |
| topic | FAM20C Raine syndrome brain defects in silico analysis gene ontology pathways |
| url | https://www.mdpi.com/1422-0067/24/10/8904 |
| work_keys_str_mv | AT icelapalmalara potentialroleofproteinkinasefam20conthebraininrainesyndromeaninsilicoanalysis AT patriciagarciaalonsothemann potentialroleofproteinkinasefam20conthebraininrainesyndromeaninsilicoanalysis AT javierperezduran potentialroleofproteinkinasefam20conthebraininrainesyndromeaninsilicoanalysis AT ricardogodinezaguilar potentialroleofproteinkinasefam20conthebraininrainesyndromeaninsilicoanalysis AT josebonilladelgado potentialroleofproteinkinasefam20conthebraininrainesyndromeaninsilicoanalysis AT damiangomezarchila potentialroleofproteinkinasefam20conthebraininrainesyndromeaninsilicoanalysis AT anamariaespinosagarcia potentialroleofproteinkinasefam20conthebraininrainesyndromeaninsilicoanalysis AT manuelnolascoquiroga potentialroleofproteinkinasefam20conthebraininrainesyndromeaninsilicoanalysis AT georginavictoriaacosta potentialroleofproteinkinasefam20conthebraininrainesyndromeaninsilicoanalysis AT adolfolopezornelas potentialroleofproteinkinasefam20conthebraininrainesyndromeaninsilicoanalysis AT juancarlosserranobello potentialroleofproteinkinasefam20conthebraininrainesyndromeaninsilicoanalysis AT mariaguadalupeolguingarcia potentialroleofproteinkinasefam20conthebraininrainesyndromeaninsilicoanalysis AT carmenpalaciosreyes potentialroleofproteinkinasefam20conthebraininrainesyndromeaninsilicoanalysis |