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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 atalogue for ransmission enetics in rabs C T G A CTGA Database Endoplasmic Reticulum Lipid Raft-Associated Protein 2 Alternative Names progressive weakness and spasticity of the lower ERLIN2 limbs. SPFH Domain-Containing Protein 2 SPFH2 Molecular Genetics Chromosome 8 Open Reading Frame 2 C8ORF2 The ERLIN2 gene resides on chromosome 8p11.2, and has 12 exons spanning approximately 25 kb in Record Category the genomic DNA. ERLIN2 has three isoforms, Gene locus two short 7-exon isoforms with alternate first exon and a long 12-exon isoform. The encoded protein WHO-ICD comprises 339 amino acids with a molecular mass N.B.: Classification not applicable to gene loci. of 38 kDa. Mutations in this gene have been associated with spastic paraplegia-18 (SPG18) Incidence per 100,000 Live Births disease, and with disease-specific survival and N/A to gene loci distant recurrence in breast cancer patients. OMIM Number Epidemiology in the Arab World 611605 Oman Mode of Inheritance N/A Al-Yahyaee et al. (2006) described two families diagnosed with autosomal recessive hereditary Gene Map Locus spastic paraplegia. The first extended family had 8p11.23 multiple consanguineous marriages with six affected individuals. In the second family, the Description parents were first cousins and had a total of seven children, three of them were affected. Using The ERLIN2 gene, also known as SPFH2 or linkage analysis for both families, a disease gene C8ORF2, encodes a member of the SPFH domain- location on chromosome 8 between markers containing family of lipid raft-associated proteins. D8S1820 and D8S532 (located on 8p12-p11.21) The encoded protein is an endoplasmic reticulum was identified. Within this interval there were two (ER) membrane protein containing a prohibitin functional candidate genes, neuregulin and domain and forms a heterodimer with Erlin1. KIF13B. Erlin2 plays a critical role in the ER associated degradation (ERAD) pathway and suppression of Saudi Arabia Erlin2 expression using RNAi leads to inhibition of polyubiquitination and proteasomal degradation of Anas et al. (2011) described an extended ERAD substrates such as inositol 1,4,5-triphosphate consanguineous Saudi family with five affected receptors and 3-hydroxy-3-methylglutaryl- members (two siblings and three maternal uncles) coenzyme A reductase. It also promotes ER with HSP. Using autozygosity mapping and retention of the SCAP-SREBF complex. linkage analysis, a novel 20 kb deletion spanning two protein-coding genes, ERLIN2 and FLJ34378 Defects in this protein are the cause of spastic (a gene of unknown function) were identified in all paraplegia-18 (SPG18), a neurodegenerative five patients. The loss of ERLIN2 initiation exons disorder characterized by a slow, gradual, along with mislocalization of exon 2 was the cause of nullimorphic allele. The ERLIN2 depletion was Copyright © Centre for Arab Genomic Studies 1 strongly associated with HSP patients, while the Van Broeckhoven C, Bayoumi RA. A novel locus deletion of FLJ34378 gene may contribute as a for hereditary spastic paraplegia with thin corpus modifier effect. callosum and epilepsy. Neurology. 2006; 66(8):1230-4. PMID: 16636240 Al-Saif et al. (2012) performed single nucleotide Anas M. Alazami, Nouran Adly, Hisham Al Dhalaan, polymorphism arrays for homozygosity mapping and Fowzan S. Alkuraya. A nullimorphic ERLIN2 for four siblings from the central region of the mutation defines a complicated hereditary spastic Arabian Peninsula affected with juvenile primary paraplegia locus (SPG18). Neurogenetics. 2011; lateral sclerosis. Homozygous splice junction 12(4): 333–336. PMID: 21796390 mutation in intron 7 of the ERLIN2 gene (c.499- 1G>T) was identified in all affecteds, resulting in Related CTGA Records an abnormal splicing of the ERLIN2 transcript and Spastic Paraplegia 18, Autosomal Recessive nonsense-mediated decay of ERLIN2 mRNA. External Links References http://www.genecards.org/cgi- Al-Saif A, Bohlega S, Al-Mohanna F. Loss of bin/carddisp.pl?gene=ERLIN2 ERLIN2 function leads to juvenile primary lateral https://ghr.nlm.nih.gov/gene/ERLIN2#conditions sclerosis. Ann Neurol. 2012; 72(4):510-6. PMID: 23109145 Contributors Al-Yahyaee S, Al-Gazali LI, De Jonghe P, Al- Nada Assaf: 8.6.2016 Barwany H, Al-Kindi M, De Vriendt E, Chand P, Koul R, Jacob PC, Gururaj A, Sztriha L, Parrado A, Copyright © Centre for Arab Genomic Studies 2 .
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