IBA57 Gene

IBA57 Gene

Introduction

Iba57 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2">IBA57 - Iron-Sulfur Cluster Assembly Factor IBA57</th></tr>
<tr><td>Full Name</td><td>Iron-Sulfur Cluster Assembly Factor IBA57</td></tr>
<tr><td>Chromosomal Location</td><td>1q42.3</td></tr>
<tr><td>NCBI Gene ID</td><td>[128308](https://www.ncbi.nlm.nih.gov/gene/128308)</td></tr>
<tr><td>OMIM</td><td>[615316](https://www.omim.org/entry/615316)</td></tr>
<tr><td>Ensembl ID</td><td>ENSG00000169189</td></tr>
<tr><td>UniProt</td><td>[Q9H1K0](https://www.uniprot.org/uniprot/Q9H1K0)</td></tr>
<tr><td>Associated Diseases</td><td>SPG74, MC4AH, MLS, Hereditary Spastic Paraplegia</td></tr>
<tr><td>Protein Class</td><td>Mitochondrial Fe-S cluster assembly factor</td></tr>
<tr><td>Expression</td><td>Mitochondria (brain, muscle, liver)</td></tr>
</table>
</div>

Overview

IBA57 (Iron-Sulfur Cluster Assembly Factor IBA57) encodes a mitochondrial matrix protein essential for the biogenesis of iron-sulfur (Fe-S) clusters, which are critical cofactors for numerous enzymes involved in energy metabolism, DNA repair, and protein synthesis. IBA57 mutations cause hereditary spastic paraplegia (SPG74), myopathy, and in severe cases, multiple congenital anomalies. The protein forms a complex with ISCA1 and ISCA2 to catalyze the final steps of Fe-S cluster maturation for specific target proteins[@sheftel2015].

IBA57 Gene

Introduction

Iba57 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2">IBA57 - Iron-Sulfur Cluster Assembly Factor IBA57</th></tr>
<tr><td>Full Name</td><td>Iron-Sulfur Cluster Assembly Factor IBA57</td></tr>
<tr><td>Chromosomal Location</td><td>1q42.3</td></tr>
<tr><td>NCBI Gene ID</td><td>[128308](https://www.ncbi.nlm.nih.gov/gene/128308)</td></tr>
<tr><td>OMIM</td><td>[615316](https://www.omim.org/entry/615316)</td></tr>
<tr><td>Ensembl ID</td><td>ENSG00000169189</td></tr>
<tr><td>UniProt</td><td>[Q9H1K0](https://www.uniprot.org/uniprot/Q9H1K0)</td></tr>
<tr><td>Associated Diseases</td><td>SPG74, MC4AH, MLS, Hereditary Spastic Paraplegia</td></tr>
<tr><td>Protein Class</td><td>Mitochondrial Fe-S cluster assembly factor</td></tr>
<tr><td>Expression</td><td>Mitochondria (brain, muscle, liver)</td></tr>
</table>
</div>

Overview

IBA57 (Iron-Sulfur Cluster Assembly Factor IBA57) encodes a mitochondrial matrix protein essential for the biogenesis of iron-sulfur (Fe-S) clusters, which are critical cofactors for numerous enzymes involved in energy metabolism, DNA repair, and protein synthesis. IBA57 mutations cause hereditary spastic paraplegia (SPG74), myopathy, and in severe cases, multiple congenital anomalies. The protein forms a complex with ISCA1 and ISCA2 to catalyze the final steps of Fe-S cluster maturation for specific target proteins[@sheftel2015].

Molecular Function

IBA57 is a mitochondrial Fe-S cluster assembly factor that functions in the late stages of 4Fe-4S cluster maturation:

• Fe-S Cluster Biogenesis: Essential cofactor for ISCA2 and ISCA1 in the mitochondrial Fe-S cluster (ISC) assembly pathway[@beilschmidt2017]
• Mitochondrial Electron Transport Chain: Required for proper assembly and function of Complex I (NADH:ubiquinone oxidoreductase), Complex II (succinate dehydrogenase), and Complex III (cytochrome bc1 complex)
• Iron-Sulfur Protein Maturation: Catalyzes insertion of 4Fe-4S clusters into specific target proteins including aconitase, ferredoxin, and respiratory complex subunits
• Mitochondrial DNA Maintenance: Indirectly supports mtDNA replication and transcription through Fe-S protein function
• Cellular Iron Homeostasis: Regulates mitochondrial iron uptake and storage to prevent oxidative damage

Expression Pattern

IBA57 is primarily expressed in tissues with high mitochondrial content:

• Brain: High expression in cerebral [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), basal ganglia, and spinal cord motor [neurons](/entities/neurons)
• Skeletal Muscle: Essential for mitochondrial function in muscle fibers
• Heart: Cardiac muscle relies heavily on oxidative phosphorylation
• Liver: High metabolic activity requires mitochondrial function
• Kidney: Renal tubular cells with high energy demands

Disease Associations

SPG74 - Hereditary Spastic Paraplegia Type 74

SPG74 is an autosomal recessive form of pure hereditary spastic paraplegia caused by IBA57 mutations[@marti2014]:

• Clinical Features: Adult-onset progressive spastic paraplegia, lower limb spasticity, weakness, and sometimes peripheral neuropathy
• Inheritance: Autosomal recessive (homozygous or compound heterozygous mutations)
• First Described: 2014 by Marti et al.
• MRI Findings: May show spinal cord atrophy

MC4AH - Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome

Severe early-onset disorder with:

• Congenital contractures (arthrogryposis)
• Hypotonia
• Seizures
• Dysmorphic features
• Often lethal in infancy

Myopathy with Lactic Acidosis

• Childhood-onset myopathy
• Exercise intolerance
• Elevated serum creatine kinase

Pathogenic Mechanisms

The neurodegeneration caused by IBA57 deficiency involves:

Therapeutic Strategies

No approved disease-modifying treatments exist:

• Gene Therapy: AAV-vector delivery of functional IBA57
• Small Molecule Mitochondrial Supporters: CoQ10, L-carnitine, B-vitamins
• Iron Chelation: Caution needed as iron is essential but can accumulate
• Supportive Care: Physical therapy, spasticity management

Animal Models

• Zebrafish: iba57 knockdown shows mitochondrial defects and motor impairment
• Mouse: Conditional knockout recapitulates spastic paraplegia phenotype
• Drosophila: Homolog Dmel\Iba57 is essential for mitochondrial function

Background

The study of Iba57 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

See Also

• [Hereditary Spastic Paraplegia](/diseases/hereditary-spastic-paraplegia)
• [Mitochondrial Dysfunction Pathway](/mechanisms/mitochondrial-dysfunction)
• Iron Metabolism in Neurodegeneration
• Complex I Deficiency
• SPG74