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    ISCA2 iron-sulfur cluster assembly 2 [ Homo sapiens (human) ]

    Gene ID: 122961, updated on 27-Nov-2024

    Summary

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    Official Symbol
    ISCA2provided by HGNC
    Official Full Name
    iron-sulfur cluster assembly 2provided by HGNC
    Primary source
    HGNC:HGNC:19857
    See related
    Ensembl:ENSG00000165898 MIM:615317; AllianceGenome:HGNC:19857
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ISA2; HBLD1; MMDS4; c14_5557
    Summary
    The protein encoded by this gene is an A-type iron-sulfur cluster (ISC) protein found in mitochondria. The encoded protein appears to be involved in the maturation of mitochondrial iron-sulfur proteins. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]
    Expression
    Ubiquitous expression in kidney (RPKM 13.2), thyroid (RPKM 12.0) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ISCA2 in Genome Data Viewer
    Location:
    14q24.3
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (74493765..74497106)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (68702736..68706077)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (74960468..74963809)

    Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene synapse differentiation inducing 1 like Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr14:74954493-74955692 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5930 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5931 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8728 Neighboring gene microRNA 4709 Neighboring gene RAP1A, member of RAS oncogene family pseudogene Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:74966807-74967802 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:74969212-74969906 Neighboring gene NPC intracellular cholesterol transporter 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:74973375-74973884 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:74976673-74977548 Neighboring gene uncharacterized LOC124903347 Neighboring gene latent transforming growth factor beta binding protein 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:74989151-74990029 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:74990491-74991430 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:74993815-74994316 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:74994959-74995460 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:75018058-75018721 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:75018722-75019386 Neighboring gene uncharacterized LOC124903346 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:75021824-75022324 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:75022325-75022825

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. ISCA2 inhibition decreases HIF and induces ferroptosis in clear cell renal carcinoma. Green YS, et al. Oncogene, 2022 Oct. PMID 36097192, Free PMC Article
    2. ISCA2 mutation causes infantile neurodegenerative mitochondrial disorder. Al-Hassnan ZN, et al. J Med Genet, 2015 Mar. PMID 25539947
    3. Loss-of-function mutations in ISCA2 disrupt 4Fe-4S cluster machinery and cause a fatal leukodystrophy with hyperglycinemia and mtDNA depletion. Alaimo JT, et al. Hum Mutat, 2018 Apr. PMID 29297947, Free PMC Article
    4. ISCA2-Related Mitochondrial Disorder. Adam MP, et al. , 1993. PMID 29470032
    5. Expanding the genotype-phenotype spectrum of ISCA2-related multiple mitochondrial dysfunction syndrome-cavitating leukoencephalopathy and prolonged survival. Hartman TG, et al. Neurogenetics, 2020 Oct. PMID 32424628

    See all (35) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Copper exerts cytotoxicity through inhibition of iron-sulfur cluster biogenesis on ISCA1/ISCA2/ISCU assembly proteins.
      Title: Copper exerts cytotoxicity through inhibition of iron-sulfur cluster biogenesis on ISCA1/ISCA2/ISCU assembly proteins.
    2. ISCA2 inhibition decreases HIF and induces ferroptosis in clear cell renal carcinoma.
      Title: ISCA2 inhibition decreases HIF and induces ferroptosis in clear cell renal carcinoma.
    3. ISCA2 deficiency leads to heme synthesis defects and impaired erythroid differentiation in K562 cells by indirect ROS-mediated IRP1 activation.
      Title: ISCA2 deficiency leads to heme synthesis defects and impaired erythroid differentiation in K562 cells by indirect ROS-mediated IRP1 activation.
    4. Characterization and Reconstitution of Human Lipoyl Synthase (LIAS) Supports ISCA2 and ISCU as Primary Cluster Donors and an Ordered Mechanism of Cluster Assembly.
      Title: Characterization and Reconstitution of Human Lipoyl Synthase (LIAS) Supports ISCA2 and ISCU as Primary Cluster Donors and an Ordered Mechanism of Cluster Assembly.
    5. Expanding the genotype-phenotype spectrum of ISCA2-related multiple mitochondrial dysfunction syndrome-cavitating leukoencephalopathy and prolonged survival.
      Title: Expanding the genotype-phenotype spectrum of ISCA2-related multiple mitochondrial dysfunction syndrome-cavitating leukoencephalopathy and prolonged survival.
    6. ISCA1 Orchestrates ISCA2 and NFU1 in the Maturation of Human Mitochondrial [4Fe-4S] Proteins.
      Title: ISCA1 Orchestrates ISCA2 and NFU1 in the Maturation of Human Mitochondrial [4Fe-4S] Proteins.
    7. Structural properties of [2Fe-2S] ISCA2-IBA57: a complex of the mitochondrial iron-sulfur cluster assembly machinery.
      Title: Structural properties of [2Fe-2S] ISCA2-IBA57: a complex of the mitochondrial iron-sulfur cluster assembly machinery.
    8. these data indicate loss of ISCA2 impaired function of 4Fe-4S proteins resulting in a fatal encephalopathy accompanied by a relatively unusual combination of features including mtDNA depletion alongside complex II deficiency and hyperglycinemia that may facilitate diagnosis of ISCA2 deficiency patients.
      Title: Loss-of-function mutations in ISCA2 disrupt 4Fe-4S cluster machinery and cause a fatal leukodystrophy with hyperglycinemia and mtDNA depletion.
    9. We identified a homoallelic missense founder mutation in ISCA2 leading to mitochondrial depletion and reduced complex I activity as well as decreased ISCA2, ISCA1 and IBA57 expression in fibroblasts.
      Title: ISCA2 mutation causes infantile neurodegenerative mitochondrial disorder.
    10. The structural plasticity of the dimeric state of the [2Fe-2S] bound form of human GRX5 is the crucial factor that allows an efficient cluster transfer to the partner proteins human ISCA1 and ISCA2 by a specific protein-protein recognition mechanism.
      Title: [2Fe-2S] cluster transfer in iron-sulfur protein biogenesis.
    Submit: New GeneRIF Correction See all GeneRIFs (13)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 2 iron, 2 sulfur cluster binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 4 iron, 4 sulfur cluster binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables iron ion binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in iron-sulfur cluster assembly IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein maturation by [4Fe-4S] cluster transfer IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    part_of mitochondrial [4Fe-4S] assembly complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    iron-sulfur cluster assembly 2 homolog, mitochondrial
    Names
    HESB-like domain-containing protein 1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_033074.1 RefSeqGene

      Range
      5046..8387
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001272007.2 → NP_001258936.1  iron-sulfur cluster assembly 2 homolog, mitochondrial isoform 2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate coding exon compared to variant 1, that causes a frameshift. The resulting isoform (2) has a shorter and distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AC005479, BX114918, BX248252, DB501282
      Consensus CDS
      CCDS61504.1
      UniProtKB/Swiss-Prot
      Q86U28
      Related
      ENSP00000450523.1, ENST00000554924.1

    2. NM_194279.4 → NP_919255.2  iron-sulfur cluster assembly 2 homolog, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_919255.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC005479, BX248252
      Consensus CDS
      CCDS32122.1
      UniProtKB/Swiss-Prot
      A6NFF1, A8K3W3, G3V291, Q86U28, Q8IYZ0, Q96BB2
      Related
      ENSP00000452007.1, ENST00000556816.6
      Conserved Domains (1) summary
      cl00400
      Location:7 → 153
      Fe-S_biosyn; Iron-sulphur cluster biosynthesis

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000014.9 Reference GRCh38.p14 Primary Assembly

      Range
      74493765..74497106
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060938.1 Alternate T2T-CHM13v2.0

      Range
      68702736..68706077
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q86U28.2 GenPept UniProtKB/Swiss-Prot:Q86U28

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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