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

Gene ID: 122961, updated on 2-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
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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

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