UNC45A

Last update 08 May 2025

Basic Info

Synonyms

GC-UNC45, GCUNC-45, Protein unc-45 homolog A

+ [6]

Introduction

Acts as a co-chaperone for HSP90. Prevents the stimulation of HSP90AB1 ATPase activity by AHSA1. Positive factor in promoting PGR function in the cell. May be necessary for proper folding of myosin (Potential). Necessary for normal cell proliferation. Necessary for normal myotube formation and myosin accumulation during muscle cell development. May play a role in erythropoiesis in stroma cells in the spleen (By similarity).

100 Clinical Results associated with UNC45A

100 Translational Medicine associated with UNC45A

0 Patents (Medical) associated with UNC45A

Literatures (Medical) associated with UNC45A

01 May 2025·Radiology Case Reports

Alazami syndrome with a single LARP7 variant and concurrent osteo-oto-hepato-enteric syndrome: A case of complex genetic interplay

Article

Author: Thouqan, Ayman ; Ghanayem, Rawan ; Janem, Abdullah ; Janem, Aya

Alazami syndrome is a rare autosomal recessive disorder characterized by primordial dwarfism, intellectual disability, and distinct facial features, primarily caused by biallelic mutations in the LARP7 gene. Osteo-oto-hepato-enteric (O2HE) syndrome is another rare autosomal recessive disorder resulting from mutations in the UNC45A gene, presenting with congenital diarrhea, neonatal cholestasis, deafness, and bone fragility. We report a unique case of an 11-month-old male patient exhibiting clinical features consistent with Alazami syndrome, including developmental delay, intellectual disability, and characteristic facial dysmorphisms (triangular face, deep-set eyes, and prominent forehead). Genetic analysis revealed a single pathogenic variant in the LARP7 gene inherited from the father, which is atypical for an autosomal recessive condition. Additionally, the patient presented with features of O2HE syndrome and was found to carry compound heterozygous mutations in the UNC45A gene. The presence of only one LARP7 variant suggests an alternative genetic mechanism, such as uniparental disomy (UPD) or a second undetected variant. This case challenges the conventional autosomal recessive inheritance model of Alazami syndrome by presenting with a single detectable LARP7 variant. It underscores the necessity for comprehensive genetic evaluations, including investigations for UPD or structural variants, in patients with suspected Alazami syndrome but only one identified pathogenic allele. Furthermore, the co-occurrence of O2HE syndrome highlights the complexity of diagnosing patients with multiple overlapping genetic disorders. This report contributes to expanding the genetic and phenotypic spectrum of Alazami syndrome and emphasizes the importance of considering multifactorial genetic mechanisms in rare congenital disorders.

01 May 2025·Current Pediatric Reviews

Newly Described Mutations of the UNC45A Gene in Infants with Jaundice and Pruritus

Article

Author: Tolmacheva, Ekaterina ; Shubina, Jekaterina ; Degtyarev, Dmitriy ; Sadelov, Igor ; Filippova, Elena ; Dokshukina, Alina ; Degtyareva, Anna ; Albegova, Marina

Background:Cholestatic liver disease is an important cause of morbidity and mortality and a leading indication for liver transplantation in children. These include diseases, such as biliary atresia, Alagille syndrome, progressive familial intrahepatic cholestasis, sclerosing cholangitis, bile acid synthesis defects, and many others.Case Presentation:NGS was used as a diagnostic tool to identify the genetic cause in the patient with cholestatic syndrome and to figure out and describe what mutation will be found. In the present observation, the cholestasis syndrome with low GGT activity and intense pruritus was the leading symptom of the patient. The examination also revealed other characteristic features of osteo- oto-hepato-enteric syndrome. The patient had facial features that mimicked Alagille syndrome, which complicated the diagnostic search. Moreover, the genetic test revealed two new pathogenic variants in the UNC45A gene.Conclusion:This clinical observation demonstrates the importance of a multidisciplinary approach in the diagnosis of rare genetic diseases and using WES, which can accelerate the diagnosis compared with outdated gene panels.

24 Mar 2025·JCI Insight

Altered chaperone–nonmuscle myosin II interactions drive pathogenicity of the UNC45A c.710T>C variant in osteo-oto-hepato-enteric syndrome

Article

Author: Dostál, Vojtěch ; Ruemmele, Frank M ; Uhlig, Holm H ; Pollio, Adam R ; Parlato, Marianna ; Vodopiutz, Julia ; Müller, Thomas ; Valovka, Taras ; Demir, Arzu Meltem ; Hess, Michael W ; Huber, Lukas A ; Kreidl, Karin ; Cerf-Bensussan, Nadine ; Adam, Rüdiger ; Waich, Stephanie ; Vogel, Georg F ; Pfaller, Kristian ; Janecke, Andreas R

The osteo-oto-hepato-enteric (O2HE) syndrome is a severe autosomal recessive disease ascribed to loss-of-function mutations in the Unc-45 myosin chaperone A (UNC45A) gene. The clinical spectrum includes bone fragility, hearing loss, cholestasis, and life-threatening diarrhea associated with microvillus inclusion disease-like enteropathy. Here, we present molecular and functional analysis of the UNC45A c.710T>C (p.Leu237Pro) missense variant, which revealed a unique pathogenicity compared with other genetic variants causing UNC45A deficiency. The UNC45A p.Leu237Pro mutant retained chaperone activity, prevented myosin aggregation, and supported proper nonmuscle myosin II (NMII) filament formation in patient fibroblasts and human osteosarcoma (U2OS) cells. However, the mutant formed atypically stable oligomers and prevented chaperone-myosin complex dissociation, thereby inhibiting NMII functions. Similar to biallelic UNC45A deficiency, this resulted in impaired intracellular trafficking, defective recycling, and abnormal retention of transferrin at various endocytic sites. In particular, coexpression of wild-type protein attenuated the pathogenic effects of the variant by inhibiting excessive oligomer formation. Our results elucidate the pathogenic mechanisms and recessive characteristics of this variant and may aid in the development of targeted therapies.

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UNC45A

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