Details for: IBA57

Gene ID: 200205

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: IBA57

Ensembl ID: ENSG00000181873

Description: iron-sulfur cluster assembly factor IBA57

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • cerebral cortex endothelial cell CL1001602
    CSI 2.86
    rCSI 4.94%
    PRS 98.03
  • erythrocyte CL0000232
    CSI 2.8
    rCSI 6.35%
    PRS 98.3
  • retinal cone cell CL0000573
    CSI 2.05
    rCSI 3.3%
    PRS 97.15
  • astrocyte of the cerebral cortex CL0002605
    CSI 2
    rCSI 4.48%
    PRS 97.11

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [IBA57](/details-gene/200205), or Iron-Sulfur Cluster Assembly Factor [IBA57](/details-gene/200205), is a mitochondrial protein encoded by the *[IBA57](/details-gene/200205)* gene located on chromosome 1. Functionally, it is essential for the maturation of [4Fe-4S] iron-sulfur cluster-containing proteins, a process critical for mitochondrial respiration and cellular metabolism [Link](https://doi.org/10.1091/mbc.e11-09-0772). Its expression profile indicates a vital role in cells with high metabolic demands. Mutations in this gene are known to cause severe autosomal recessive disorders, including myopathy, encephalopathy, and hereditary spastic paraplegia, highlighting its fundamental importance in human health [Link](https://doi.org/10.1093/hmg/ddt107), [Link](https://doi.org/10.1212/wnl.0000000000001270). ## Cellular Roles and Expression Landscape The expression pattern of [IBA57](/details-gene/200205) underscores its role as a fundamental component of cellular metabolism, particularly in tissues with high energy requirements. **Overall**, the gene shows significant expression in a diverse set of cell types, rather than being restricted to a specific lineage. Key cell types with high significance scores for [IBA57](/details-gene/200205) include: * **Central Nervous System Cells:** It is a significant marker in [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 2.86) and [astrocyte of the cerebral cortex](/details-cell/CL0002605) (CSI: 2.00). This is consistent with the high metabolic activity of the brain and the critical role of these cells in supporting neuronal function and maintaining the blood-brain barrier. * **Hematopoietic Cells:** High significance is observed in [erythrocyte](/details-cell/CL0000232) (CSI: 2.80). This may relate to its involvement in the [Heme biosynthetic process](/details-ontology/GO:0006783), which is a core function of red blood cell precursors. * **Photoreceptor Cells:** The gene is also highly significant in [retinal cone cell](/details-cell/CL0000573) (CSI: 2.05), a cell type with one of the highest metabolic rates in the body, required for vision. This broad but specific expression profile in high-energy cells from the nervous, circulatory, and visual systems suggests that [IBA57](/details-gene/200205) is not a cell identity marker but rather a critical "workhorse" gene essential for maintaining core mitochondrial function across metabolically active tissues. ## Pathways and Molecular Function [IBA57](/details-gene/200205) is localized to the [mitochondrial matrix](/details-ontology/GO:0005759) and is a key player in the [Iron-sulfur cluster assembly](/details-ontology/GO:0016226) pathway. Iron-sulfur (Fe-S) clusters are ancient and ubiquitous cofactors essential for the function of numerous proteins involved in electron transport, enzyme catalysis, and DNA repair. Research has demonstrated that [IBA57](/details-gene/200205), along with ISCA1 and ISCA2, is specifically required for the final steps of [4Fe-4S] cluster assembly and their subsequent insertion into apoproteins [Link](https://doi.org/10.1091/mbc.e11-09-0772). This function is critical for the activity of mitochondrial respiratory chain complexes I, II, and III, as well as other vital mitochondrial enzymes. The gene's annotation for [Transferase activity](/details-ontology/GO:0016740) reflects its role in this molecular assembly line. Its involvement in the [Heme biosynthetic process](/details-ontology/GO:0006783) further links it to fundamental mitochondrial pathways that are particularly active in cell types like erythrocytes. ## Research Directions The severe neurological and muscular phenotypes associated with [IBA57](/details-gene/200205) mutations, combined with its expression profile, suggest clear avenues for further investigation. The gene's function points directly to a pathology rooted in mitochondrial bioenergetic failure. Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis 1:** The high significance of [IBA57](/details-gene/200205) in [cerebral cortex endothelial cell](/details-cell/CL1001602) suggests that its dysfunction contributes to the encephalopathy phenotype by compromising blood-brain barrier (BBB) integrity. Defective mitochondrial respiration in these cells could lead to a breakdown in tight junctions and increased permeability, exacerbating neuronal damage. 2. **Hypothesis 2:** The pronounced significance in [retinal cone cell](/details-cell/CL0000573) indicates that [IBA57](/details-gene/200205) is indispensable for photoreceptor survival and function. Loss-of-function mutations likely lead to progressive vision loss or retinal dysfunction as a clinical feature in patients, a consequence of the inability to meet the high energetic demands of phototransduction. A key experiment to test the first hypothesis could involve an *in vitro* model of the human BBB. CRISPR-Cas9-mediated knockout of [IBA57](/details-gene/200205) in human brain microvascular endothelial cells, cultured alone or in co-culture with astrocytes, could be performed. The impact on BBB integrity could then be quantified by measuring transendothelial electrical resistance (TEER) and the permeability to size-exclusion fluorescent dextrans. A significant decrease in TEER and an increase in permeability following [IBA57](/details-gene/200205) knockout would support its critical role in BBB maintenance. **Therapeutic Potential:** As the diseases associated with [IBA57](/details-gene/200205) are severe, monogenic, loss-of-function disorders, the therapeutic strategy would focus on functional restoration rather than inhibition. Gene therapy, aiming to deliver a functional copy of the *[IBA57](/details-gene/200205)* gene to affected tissues like the central nervous system and muscle, represents the most promising long-term approach. However, challenges related to efficient delivery across the BBB and specific targeting of mitochondria remain significant hurdles to clinical implementation.

Genular Protein ID: 1903948057

Symbol: CAF17_HUMAN

Name: Putative transferase CAF17, mitochondrial

UniProtKB Accession Codes:

Q5T440

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 1 Ensembl 1 GO 6 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 5 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 1 SASBDB 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22323289

Title: The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation.

PubMed ID: 22323289

DOI: 10.1091/mbc.e11-09-0772

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 25609768

Title: Fe/S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia.

PubMed ID: 25609768

DOI: 10.1212/wnl.0000000000001270

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 23462291

Title: Mutation of the iron-sulfur cluster assembly gene IBA57 causes severe myopathy and encephalopathy.

PubMed ID: 23462291

DOI: 10.1093/hmg/ddt107

Sequence Information:

  • Length: 356
  • Mass: 38155
  • Checksum: 199A04DAB6840807
  • Sequence:
    • MATAALLRGA TPGRGGPVWR WRLRAAPRCR LAHSSCSPGG DPTAGAAWAC FRLDGRTLLR 
VRGPDAAPFL LGLLTNELPL PSPAAAGAPP AARAGYAHFL NVQGRTLYDV ILYGLQEHSE 
VSGFLLECDS SVQGALQKHL ALYRIRRKVT VEPHPELRVW AVLPSSPEAC GAASLQERAG 
AAAILIRDPR TARMGWRLLT QDEGPALVPG GRLGDLWDYH QHRYLQGVPE GVRDLPPGVA 
LPLESNLAFM NGVSFTKGCY IGQELTARTH HMGVIRKRLF PVRFLDPLPT SGITPGATVL 
TASGQTVGKF RAGQGNVGLA LLWSEKIKGP LHIRASEGAQ VALAASVPDW WPTVSK

Genular Protein ID: 3468799152

Symbol: B4E1G9_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4E1G9

Database IDs:

ARBA 2 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 2 InterPro 3 NCBI Taxonomy 1 NCBIfam 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 RefSeq 1 SUPFAM 1

Sequence Information:

  • Length: 163
  • Mass: 17632
  • Checksum: 8D5A7FEECDE58BE9
  • Sequence:
    • MGWRLLTQDE GPALVPGSRL GDLWDYHQHR YLQGVPEGVR DLPPGVALPL ESNLAFMNGV 
SFTKGCYIGQ ELTARTHHMG VIRKRLFPVR FLDPLPTSGI TPGATVLTAS GQTVGKFRAG 
QGNVGLALLW SEKIKGPLHI RASEGAQVAL AASVPDWWPT VSK