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    ISCU iron-sulfur cluster assembly enzyme [ Homo sapiens (human) ]

    Gene ID: 23479, updated on 5-Mar-2024

    Summary

    Official Symbol
    ISCUprovided by HGNC
    Official Full Name
    iron-sulfur cluster assembly enzymeprovided by HGNC
    Primary source
    HGNC:HGNC:29882
    See related
    Ensembl:ENSG00000136003 MIM:611911; AllianceGenome:HGNC:29882
    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
    HML; ISU2; NIFU; NIFUN; hnifU; 2310020H20Rik
    Summary
    This gene encodes a component of the iron-sulfur (Fe-S) cluster scaffold. Fe-S clusters are cofactors that play a role in the function of a diverse set of enzymes, including those that regulate metabolism, iron homeostasis, and oxidative stress response. Alternative splicing results in transcript variants encoding different protein isoforms that localize either to the cytosol or to the mitochondrion. Mutations in this gene have been found in patients with hereditary myopathy with lactic acidosis. A disease-associated mutation in an intron may activate a cryptic splice site, resulting in the production of a splice variant encoding a putatively non-functional protein. A pseudogene of this gene is present on chromosome 1. [provided by RefSeq, Feb 2016]
    Expression
    Ubiquitous expression in adrenal (RPKM 47.9), heart (RPKM 43.2) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See ISCU in Genome Data Viewer
    Location:
    12q23.3
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (108561463..108569384)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (108530831..108538753)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (108955239..108963160)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:108910488-108910988 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:108910989-108911489 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr12:108918373-108919572 Neighboring gene FIC domain protein adenylyltransferase Neighboring gene spliceosome associated factor 3, U4/U6 recycling protein Neighboring gene MPRA-validated peak1936 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6962 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4827 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6963 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6964 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6965 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6966 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6967 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4828 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4829 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6968 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6969 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:108976096-108976273 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:108982554-108983282 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:108987423-108988089 Neighboring gene transmembrane protein 119 Neighboring gene Sharpr-MPRA regulatory region 9141 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6970 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6971 Neighboring gene uncharacterized LOC105369968 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6972 Neighboring gene selectin P ligand Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6973

    Genomic regions, transcripts, and products

    Expression

    • 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Hereditary myopathy with lactic acidosis due to ISCU deficiency
    MedGen: C1850718 OMIM: 255125 GeneReviews: Not available
    Compare labs

    EBI GWAS Catalog

    Description
    Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris.
    EBI GWAS Catalog

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • MGC74517

    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 ferrous iron binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables iron ion binding TAS
    Traceable Author Statement
    more info
    PubMed 
    enables molecular adaptor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables zinc ion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    part_of iron-sulfur cluster assembly complex NAS
    Non-traceable Author Statement
    more info
    PubMed 
    part_of mitochondrial iron-sulfur cluster assembly complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in mitochondrial matrix IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
     
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in mitochondrion NAS
    Non-traceable Author Statement
    more info
    PubMed 
    located_in nucleus TAS
    Traceable Author Statement
    more info
    PubMed 

    General protein information

    Preferred Names
    iron-sulfur cluster assembly enzyme ISCU
    Names
    IscU iron-sulfur cluster scaffold homolog
    iron-sulfur cluster assembly enzyme ISCU, mitochondrial
    nifU-like N-terminal domain-containing protein

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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_011857.1 RefSeqGene

      Range
      5079..11851
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001301140.1NP_001288069.1  iron-sulfur cluster assembly enzyme ISCU isoform 3 precursor

      See identical proteins and their annotated locations for NP_001288069.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) contains an alternate exon in the 3' region, resulting in a different 3' coding region and 3' UTR, compared to variant 2. Variants 3 and 5 encode the same protein (isoform 3), which has a distinct, shorter C-terminus, compared to isoform 2. Isoform 3 may not be stable (PMID:23035118). This variant may be preferentially produced in individuals containing an alternate intronic C vs G (rs767000507), which activates a cryptic splice acceptor site. The alternate C allele is associated with myopathy (PMIDs 18296749, 18304497).
      Source sequence(s)
      AK057251, BG702203, BQ020993
      Consensus CDS
      CCDS76597.1
      UniProtKB/TrEMBL
      B4DNC9, F5H5N2
      Related
      ENSP00000446606.1, ENST00000547005.5
      Conserved Domains (1) summary
      cl00528
      Location:35139
      IscU_like; Iron-sulfur cluster scaffold-like proteins
    2. NM_001301141.1NP_001288070.1  iron-sulfur cluster assembly enzyme ISCU isoform 4 precursor

      See identical proteins and their annotated locations for NP_001288070.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) contains an alternate exon in the 3' region, resulting in a different 3' coding region and 3' UTR, compared to variant 2. The encoded isoform (4) has a distinct, shorter C-terminus, compared to isoform 2.
      Source sequence(s)
      AC008119, AK057251, BQ020993
      Consensus CDS
      CCDS73518.1
      UniProtKB/TrEMBL
      B3KQ30, F5H5N2
      Related
      ENSP00000411108.2, ENST00000431221.6
      Conserved Domains (1) summary
      cl00528
      Location:35139
      IscU_like; Iron-sulfur cluster scaffold-like proteins
    3. NM_001320042.1NP_001306971.1  iron-sulfur cluster assembly enzyme ISCU isoform 3 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) uses an alternate splice site in the 3' region, resulting in a different 3' coding region and 3' UTR, compared to variant 2. Variants 3 and 5 encode the same protein (isoform 3), which has a distinct, shorter C-terminus, compared to isoform 2. Isoform 3 may not be stable (PMID:23035118). This variant may be preferentially produced in individuals containing an alternate intronic C vs G (rs767000507), which activates a cryptic splice acceptor site. The alternate C allele is associated with myopathy (PMIDs 18296749, 18304497).
      Source sequence(s)
      AK057251, AK297862, BC061903, HY269565
      Consensus CDS
      CCDS76597.1
      UniProtKB/TrEMBL
      B4DNC9, F5H5N2
      Related
      ENSP00000445598.1, ENST00000535729.5
      Conserved Domains (1) summary
      cl00528
      Location:35139
      IscU_like; Iron-sulfur cluster scaffold-like proteins
    4. NM_014301.4NP_055116.1  iron-sulfur cluster assembly enzyme ISCU isoform 1

      See identical proteins and their annotated locations for NP_055116.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) contains an alternate exon in the 5' region and initiates translation at an alternate start codon compared to variant 2. The encoded isoform (1) has a distinct, shorter N-terminus, compared to isoform 2. Isoform 1 is localized to the cytosol.
      Source sequence(s)
      AK057251, AY009127, BQ020993
      Consensus CDS
      CCDS9118.1
      Related
      ENSP00000376554.4, ENST00000392807.8
      Conserved Domains (1) summary
      PRK11325
      Location:11133
      PRK11325; scaffold protein; Provisional
    5. NM_213595.4NP_998760.1  iron-sulfur cluster assembly enzyme ISCU isoform 2 precursor

      See identical proteins and their annotated locations for NP_998760.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) encodes the longest isoform (2). Isoform 2 is localized to the mitochondrion.
      Source sequence(s)
      AK057251, BC011906, BQ020993
      Consensus CDS
      CCDS44966.1
      UniProtKB/Swiss-Prot
      Q6P713, Q99617, Q9H1K1, Q9H1K2
      UniProtKB/TrEMBL
      F5H5N2
      Related
      ENSP00000310623.9, ENST00000311893.14
      Conserved Domains (1) summary
      PRK11325
      Location:35158
      PRK11325; scaffold protein; Provisional

    RNA

    1. NR_135127.1 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) contains an alternate exon in the 5' region and an alternate exon in the 3' region, compared to variant 2. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD). This variant may be preferentially produced in individuals containing an alternate intronic C vs G (rs767000507), which activates a cryptic splice acceptor site. The alternate C allele is associated with myopathy (PMIDs 18296749, 18304497).
      Source sequence(s)
      AK057251, BC061903, EU329002

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      108561463..108569384
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047428627.1XP_047284583.1  iron-sulfur cluster assembly enzyme ISCU isoform X1

      UniProtKB/TrEMBL
      B1P7G3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      108530831..108538753
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054371605.1XP_054227580.1  iron-sulfur cluster assembly enzyme ISCU isoform X1

      UniProtKB/TrEMBL
      B1P7G3