Ask about this productRelated genes to: C12ORF4 antibody
- Gene:
- C12orf4 NIH gene
- Name:
- chromosome 12 open reading frame 4
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 12p13.32
- Locus Type:
- gene with protein product
- Date approved:
- 2000-08-24
- Date modifiied:
- 2019-03-27
Related products to: C12ORF4 antibody
Related articles to: C12ORF4 antibody
- TBCK syndrome is a severe neurodevelopmental disorder characterized by hypotonia, intellectual disability, and progressive neurodegeneration. While the gene has been implicated in MTOR signaling, its primary molecular function has remained controversial. In a recent study, we identify TBCK as the catalytic core of a heterotrimeric complex comprising TBCK, PPP1R21, and FERRY3/C12orf4. This complex functions as a specific GTPase-activating protein (GAP) for RAB5. deficiency or missense mutations of its key residues in the RABGAP-TBC domain lead to constitutive RAB5 hyperactivation, which blocks the transition from early to late endosomes and results in the formation of massively enlarged RAB5-positive endosomes. Furthermore, this RAB5 hyperactivation drives the constitutive activation of the PIK3C3/VPS34 complex. These defects culminate in a failure of lysosomal enzyme delivery and a secondary collapse of macroautophagic/autophagic flux. These findings redefine TBCK syndrome as a primary disorder of endosomal dynamics and highlight the TBCK-PPP1R21-FERRY3 axis as a critical "brake" for maintaining neuronal homeostasis. - Source: PubMed
Publication date: 2026/03/11
Chen YingjiXu XiayunZheng YiWang HongyanWang Chenji - - Source: PubMed
Publication date: 2025/10/25
Wang YalanXu XiayunCao XiaotongHe HuiyingQin YueDeng TingZhang ZhigangWu LingqianWang ChenjiWang Hongyan - Monogenic pediatric neurodegenerative disorders can reveal fundamental cellular mechanisms that underlie selective neuronal vulnerability. TBCK-Encephaloneuronopathy (TBCKE) is a rare autosomal recessive disorder caused by stop-gain variants in the gene. Clinically, patients show evidence of profound neurodevelopmental delays, but also symptoms of progressive encephalopathy and motor neuron disease. Yet, the physiological role of TBCK protein remains unclear. We report a human neuronal TBCKE model, derived from iPSCs homozygous for the Boricua variant (p.R126X). Using unbiased proteomic analyses of human neurons, we find TBCK interacts with PPP1R21, C12orf4, and Cryzl1, consistent with TBCK being part of the FERRY mRNA transport complex. Loss of TBCK leads to depletion of C12ORF4 protein levels across multiple cell types, suggesting TBCK may also play a role regulating at least some members of the FERRY complex. We find that TBCK preferentially, but not exclusively, localizes to the surface of endolysosomal vesicles and can colocalize with mRNA in lysosomes. Furthermore, TBCK-deficient neurons have reduced mRNA content in the axonal compartment relative to the soma. TBCK-deficient neurons show reduced levels of the lysosomal dynein/dynactin adapter protein JIP4, which functionally leads to TBCK-deficient neurons exhibiting striking lysosomal axonal retrograde trafficking defects. Hence, our work reveals that TBCK can mediate endolysosomal trafficking of mRNA, particularly along lysosomes in human axonal compartments. TBCK-deficiency leads to compartment-specific mRNA and lysosomal trafficking defects in neurons, which likely contribute to the preferential susceptibility to neurodegeneration. - Source: PubMed
Publication date: 2025/03/07
Flores-Mendez MarcoTintos-Hernández Jesus ARamos-Rodriguez LeonardoMiles LeannLo Tsz YSong YuanquanOrtiz-González Xilma R - The five-subunit endosomal Rab5 and RNA/ribose intermediary (FERRY) complex is a newly described protein complex consisting of TBCK, PPP1R21, FERRY3 (previously C12orf4), CRYZL1, and GATD1. The FERRY complex is proposed to function as a Rab5 effector to shuttle mRNA to the cell periphery for local translation, a process especially important in cells with far reaching processes. Interestingly, three members of the FERRY complex are associated with ultra-rare neurogenetic disorders. Mutation of TBCK causes TBCK syndrome, mutation of PPP1R21 is associated with PPP1R21-related intellectual disability, and mutation of FERRY3 results in an autosomal recessive intellectual disability. Neurologic disorders have yet to be associated with mutation of GATD1 or CRYZL1. Here, we provide a review of each FERRY complex-related neurologic disorder and draw clinical comparisons between the disease states. We also discuss data from the current cellular and animal models available to study these disorders, which is notably disparate and scattered across different cell types and systems. Taken together, we explore the possibility that these three diseases may represent one shared disease class, which could be further understood by combining and comparing known information about each individual disease. If true, this could have substantial implications on our understanding of the cellular role of the FERRY complex and on treatment strategies for affected individuals, allowing researchers, clinicians, and patient organizations to maximize the utility of research efforts and resources to support patients with these disorders. - Source: PubMed
Publication date: 2025/03/10
Riffe R MadisonDownes Gerald B - Intellectual disability (ID) is a hallmark of many rare disorders that are highly heterogeneous and complex. A large number of specific genes are involved in development of this heterogeneity, and each of these genes is only found in a small number of patients. This weakens the definition of the predominant genotype and the phenotypic characteristics associated with that gene. Autosomal recessive ID type 66 (OMIM #618221) is one of these very rare diseases created by defects in the C12orf4 gene. - Source: PubMed
Publication date: 2022/01/31
Rashvand ZahraKahrizi KimiaNajmabadi HosseinNajafipour RezaOmrani Mir Davood