Centre for Arab Genomic Studies a Division of Sheikh Hamdan Award for Medical Sciences

Centre for Arab Genomic Studies A Division of Sheikh Hamdan Award for Medical Sciences

The Catalogue for Transmission Genetics in Arabs CTGA Database

ATP/GTP-Binding Protein 1

Alternative Names cells. Analysis of pcd mice has shown increased AGTPBP1 levels of tubulin polyglutamylation in the brain. Nervous System Nuclear Protein Induced by Axotomy Molecular Genetics NNA1 The AGTPBP1 gene is located on the long arm of KIAA1035 chromosome 9 at position 9q21.33. The gene spans Cytosolic Carboxypeptidase 1 a length of 195.4 kb of DNA and its coding CCP1 sequence is spread across 31 exons. Several additional isoforms of the AGTPBP1 gene exist due Record Category to alternatively spliced transcript variants. While Gene locus the gene is widely expressed in the human body, overexpression is seen in the fetal brain, retina and WHO-ICD peripheral blood mononuclear cells. N/A to gene loci Epidemiology in the Arab World Incidence per 100,000 Live Births Saudi Arabia N/A to gene loci Monies et al. (2017) analyzed the findings of 1000 diagnostic panels and exomes carried out at a next OMIM Number generation sequencing lab in Saudi Arabia. One 606830 patient, a 2-year-old female, presented with congenital hypotonia and global developmental Mode of Inheritance delay. She was found to suffer from diffuse N/A to gene loci atrophic changes of the brain indicated by diminished myelinated white matter volume, Gene Map Locus deepened sulci, dilated ventricular system, thinned 9q21.33 corpus callosum, increased mamillo-potine distance and significantly prominent extra axial CSF spaces. Description Using WES, a homozygous mutation (c.2908C>T, The AGTPBP1 gene, also known as CCP1, encodes p.R970W) was identified in exon 20 of the patient’s a zinc carboxypeptidase enzyme that is responsible AGTPBP1 gene. This gene mutation was for catalysing the deglutamylation of target considered a candidate for pathogenicity as it was a proteins. CCP1 can carry out the deglutamylation of novel variant located within the autozygome that polyglutamate side chains added by post- was predicted to be deleterious, and mutations in translational modification to the C-termini of the mouse orthologue of the AGTPBP1 gene have tubulin proteins. It can also mediate the been shown to result in cerebellar Purkinje neuron deglutamylation of gene-encoded polyglutamates degeneration. The authors noted that further studies from proteins such as MYLK. are required to independently confirm this association. Mouse models have helped elucidate the physiological role of CCP1. The mouse orthologue References gene, Ccp1, is found to be mutated in the Purkinje Monies D, Abouelhoda M, AlSayed M, Alhassnan cell degeneration (pcd) phenotype of mice. These Z, Alotaibi M, Kayyali H, Al-Owain M, Shah A, pcd mice exhibit ataxia subsequent to cerebellar Rahbeeni Z, Al-Muhaizea MA, Alzaidan HI, Purkinje cell degeneration. They also suffer the Cupler E, Bohlega S, Faqeih E, Faden M, Alyounes progressive deterioration of thalamic neurons, B, Jaroudi D, Goljan E, Elbardisy H, Akilan A, retinal photoreceptors and olfactory bulb mitral Albar R, Aldhalaan H, Gulab S, Chedrawi A, Al Saud BK, Kurdi W, Makhseed N, Alqasim T, El

Khashab HY, Al-Mousa H, Alhashem A, Kanaan I, Alfadhel M, Faquih T, El-Kalioby M, Subhani S, Algoufi T, Alsaleem K, Basha TA, Al-Murshedi F, Shah Z, Moghrabi N, Meyer BF, Alkuraya FS. The Khan S, Al-Kindy A, Alnemer M, Al-Hajjar S, landscape of genetic diseases in Saudi Arabia based Alyamani S, Aldhekri H, Al-Mehaidib A, Arnaout on the first 1000 diagnostic panels and exomes. R, Dabbagh O, Shagrani M, Broering D, Tulbah M, Hum Genet. 2017 Aug;136(8):921-939. PMID: Alqassmi A, Almugbel M, AlQuaiz M, Alsaman A, 28600779. Al-Thihli K, Sulaiman RA, Al-Dekhail W, Alsaegh A, Bashiri FA, Qari A, Alhomadi S, Alkuraya H, Related CTGA Records Alsebayel M, Hamad MH, Szonyi L, Abaalkhail F, Al-Mayouf SM, Almojalli H, Alqadi KS, Elsiesy H, External Links Shuaib TM, Seidahmed MZ, Abosoudah I, Akleh http://www.genecards.org/cgi- H, AlGhonaium A, Alkharfy TM, Al Mutairi F, bin/carddisp.pl?gene=AGTPBP1 Eyaid W, Alshanbary A, Sheikh FR, Alsohaibani FI, Alsonbul A, Al Tala S, Balkhy S, Bassiouni R, Contributors Alenizi AS, Hussein MH, Hassan S, Khalil M, Sayeeda Hana Tabarki B, Alshahwan S, Oshi A, Sabr Y, 03.08.2017 Alsaadoun S, Salih MA, Mohamed S, Sultana H, Tamim A, El-Haj M, Alshahrani S, Bubshait DK,