OFD1

更新于：2025-05-07

基本信息

别名

71-7A、Centriole and centriolar satellite protein OFD1、CXorf5

+ [6]

简介

Component of the centrioles controlling mother and daughter centrioles length. Recruits to the centriole IFT88 and centriole distal appendage-specific proteins including CEP164 (By similarity). Involved in the biogenesis of the cilium, a centriole-associated function. The cilium is a cell surface projection found in many vertebrate cells required to transduce signals important for development and tissue homeostasis (PubMed:33934390). Plays an important role in development by regulating Wnt signaling and the specification of the left-right axis. Only OFD1 localized at the centriolar satellites is removed by autophagy, which is an important step in the ciliogenesis regulation (By similarity).

关联

100 项与 OFD1 相关的临床结果

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100 项与 OFD1 相关的转化医学

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0 项与 OFD1 相关的专利（医药）

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216

项与 OFD1 相关的文献（医药）

2025-06-01·Genetics in Medicine

Identification of IDH3G, encoding the gamma subunit of mitochondrial isocitrate dehydrogenase, as a novel candidate gene for X-linked retinitis pigmentosa

Article

作者: Zeitz, Christina ; El Shamieh, Said ; Audo, Isabelle ; Sangermano, Riccardo ; Bianco, Lorenzo ; Bujakowska, Kinga M ; Mansard, Luke ; Kalatzis, Vasiliki ; Meunier, Isabelle ; Pierce, Eric A ; Antonio, Aline ; Andrieu, Camille ; Smirnov, Vasily ; Navarro, Julien ; Condroyer, Christel ; Place, Emily M ; Michiels, Christelle ; Bocquet, Béatrice ; Sahel, José-Alain ; Roux, Anne-Françoise ; Antropoli, Alessio

PURPOSERetinitis pigmentosa (RP) is a genetically heterogeneous group of retinal degenerative disorders characterized by the loss of rod and cone photoreceptors, leading to visual impairment and blindness. To date, to our knowledge, X-linked RP has been associated with variants in 3 genes (RPGR, RP2, and OFD1), whereas genetic defects at 3 loci (RP6, RP24, and RP34) are yet unidentified. The aim of this study was to identify a novel candidate gene underlying X-linked RP.METHODSParticipants were identified from cohorts of genetically unsolved male individuals affected by RP, who underwent genome sequencing, exome sequencing, or candidate gene screening via direct Sanger sequencing at 3 referral centers. Specifically, 2 probands were identified at the National Reference Centre for Rare Retinal Diseases (Paris, France), 2 at the Massachusetts Eye and Ear Hospital (Boston, MA), and 1 at the National Reference Centre for Inherited Sensory Diseases (Montpellier, France). The pathogenicity of the identified variants was assessed using bioinformatic predictions, protein expression analyses, and mitochondrial function assays.RESULTSWe identified 4 rare single-nucleotide variants in IDH3G (HGNC:5386), located at the RP34 locus on the X chromosome, and a complete gene deletion, in 5 unrelated male individuals affected with nonsyndromic RP. The variants segregated with the phenotype in all available family members. In all cases, the disease severity was intermediate. None had high myopia. IDH3G encodes the γ subunit of mitochondrial isocitrate dehydrogenase (IDH3), an enzyme involved in the citric acid cycle, which is expressed in the inner segments of photoreceptors. Variants in IDH3A and IDH3B, encoding the other subunits of IDH3, have already been associated with nonsyndromic autosomal recessive RP. Bioinformatic predictions and functional assays support a pathogenic role for the variants identified in this study, possibly through partial loss of enzymatic activity and mitochondrial function.CONCLUSIONOur findings suggest that variants in IDH3G are a novel cause of X-linked RP.

2025-04-01·The International Journal of Biochemistry & Cell Biology

SIRT2 inhibition attenuates myofibroblast transition through autophagy-mediated ciliogenesis in renal epithelial cells

Article

作者: Son, Juyoung ; Park, Jaejung ; Kim, Ja-Eun ; Jeong, Joo-Won ; Lee, Seung Hyeun

Myofibroblast transition plays a crucial role in both fibrotic diseases and wound healing. Although SIRT2 regulates fibrosis, its mechanisms of action remain poorly understood. This study aimed to investigate the effects of SIRT2 inhibition on myofibroblast transition in human renal cells under quiescent conditions. HK-2 kidney proximal tubular epithelial cells were starved of serum, resulting in the formation of primary cilia. Transforming growth factor-β (TGF-β) stimulation reduced both the number of ciliated cells and ciliary length. The ciliary defects resulted from a failure in autophagy termination, leading to the accumulation of OFD1, a negative regulator of ciliogenesis, at centriolar satellites. This phenomenon was correlated with the upregulation of fibrosis-related proteins. To elucidate the role of SIRT2 in the autophagy-ciliogenesis-fibrosis axis, cells were treated with AGK2, a specific inhibitor of SIRT2. AGK2 treatment promoted the formation of both autophagosomes and autolysosomes and facilitated OFD1 degradation at the centriolar satellites, resulting in the lengthening of primary cilia. Restoration of primary cilia by AGK2 was associated with the suppression of myofibroblast transition. In conclusion, SIRT2 inhibition attenuates TGF-β-induced fibrosis by promoting autophagy-mediated ciliogenesis. This study highlights SIRT2 as a potential therapeutic target for fibrotic diseases.

2025-01-01·The American Journal of Human Genetics

Chromosome X-wide common variant association study in autism spectrum disorder

Article

作者: Scherer, Stephen W ; Salazar, Nelson Bautista ; Sun, Lei ; Roshandel, Delnaz ; Bandres-Ciga, Sara ; Alexandrova, Roumiana ; Trost, Brett ; Mendes, Marla ; Pellecchia, Giovanna ; Thiruvahindrapuram, Bhooma ; Lai, Meng-Chuan ; Bradley, Clarrisa A ; Anagnostou, Evdokia ; Rivera-Alfaro, Natalia ; Leal, Thiago Peixoto ; McKee, Ethan A ; Nalpathamkalam, Thomas ; Chen, Desmond Zeya ; Howe, Jennifer L ; Engchuan, Worrawat

Autism spectrum disorder (ASD) displays a notable male bias in prevalence. Research into rare (<0.1) genetic variants on the X chromosome has implicated over 20 genes in ASD pathogenesis, such as MECP2, DDX3X, and DMD. The "female protective effect" in ASD suggests that females may require a higher genetic burden to manifest symptoms similar to those in males, yet the mechanisms remain unclear. Despite technological advances in genomics, the complexity of the biological nature of sex chromosomes leaves them underrepresented in genome-wide studies. Here, we conducted an X-chromosome-wide association study (XWAS) using whole-genome sequencing data from 6,873 individuals with ASD (82% males) across Autism Speaks MSSNG, Simons Simplex Collection (SSC), and Simons Powering Autism Research (SPARK), alongside 8,981 population controls (43% males). We analyzed 418,652 X chromosome variants, identifying 59 associated with ASD (p values 7.9 × 10^-6 to 1.51 × 10^-5), surpassing Bonferroni-corrected thresholds. Key findings include significant regions on Xp22.2 (lead SNP rs12687599, p = 3.57 × 10^-7) harboring ASB9/ASB11 and another encompassing DDX53 and the PTCHD1-AS long non-coding RNA (lead SNP rs5926125, p = 9.47 × 10^-6). When mapping genes within 10 kb of the 59 most significantly associated SNPs, 91 genes were found, 17 of which yielded association with ASD (GRPR, AP1S2, DDX53, HDAC8, PCDH19, PTCHD1, PCDH11X, PTCHD1-AS, DMD, SYAP1, CNKSR2, GLRA2, OFD1, CDKL5, GPRASP2, NXF5, and SH3KBP1). FGF13 emerged as an X-linked ASD candidate gene, highlighted by sex-specific differences in minor allele frequencies. These results reveal significant insights into X chromosome biology in ASD, confirming and nominating genes and pathways for further investigation.

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