This gene encodes a DnaJ-type co-chaperone and member of the heat shock cognate B (HscB) family of proteins. The encoded protein plays a role in the synthesis of iron-sulfur clusters, protein cofactors that are involved in the redox reactions of mitochondrial electron transport and other processes. Cells in which this gene is knocked down exhibit reduced activity of iron-sulfur... See more...

Aliases for HSCB Gene

Aliases for HSCB Gene

  • HscB Mitochondrial Iron-Sulfur Cluster Cochaperone 2 3 5
  • DNAJC20 2 3 4
  • HSC20 2 3 4
  • Iron-Sulfur Cluster Co-Chaperone Protein HscB 3 4
  • DnaJ (Hsp40) Homolog, Subfamily C, Member 20 2 3
  • Iron-Sulfur Cluster Co-Chaperone Protein HscB, Mitochondrial 3
  • HscB Iron-Sulfur Cluster Co-Chaperone Homolog (E. Coli) 2
  • HscB Mitochondrial Iron-Sulfur Cluster Co-Chaperone 3
  • HscB Iron-Sulfur Cluster Co-Chaperone Homolog 3
  • Epididymis Secretory Sperm Binding Protein 3
  • DnaJ Homolog Subfamily C Member 20 4
  • J-Type Co-Chaperone HSC20 3
  • JAC1 3
  • HSCB 5
  • Jac1 2

External Ids for HSCB Gene

Previous GeneCards Identifiers for HSCB Gene

  • GC22P027468
  • GC22P029138
  • GC22P012103

Summaries for HSCB Gene

Entrez Gene Summary for HSCB Gene

  • This gene encodes a DnaJ-type co-chaperone and member of the heat shock cognate B (HscB) family of proteins. The encoded protein plays a role in the synthesis of iron-sulfur clusters, protein cofactors that are involved in the redox reactions of mitochondrial electron transport and other processes. Cells in which this gene is knocked down exhibit reduced activity of iron-sulfur cluster-dependent enzymes including succinate dehydrogenase and aconitase. The encoded protein may stimulate the ATPase activity of the mitochondrial stress-70 protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

GeneCards Summary for HSCB Gene

HSCB (HscB Mitochondrial Iron-Sulfur Cluster Cochaperone) is a Protein Coding gene. Diseases associated with HSCB include Anemia, Sideroblastic, And Spinocerebellar Ataxia and Combined Oxidative Phosphorylation Deficiency 19. Among its related pathways are Metabolism of proteins and Mitochondrial protein import. Gene Ontology (GO) annotations related to this gene include chaperone binding.

UniProtKB/Swiss-Prot Summary for HSCB Gene

  • Acts as a co-chaperone in iron-sulfur cluster assembly in both mitochondria and the cytoplasm (PubMed:20668094, PubMed:29309586). Required for incorporation of iron-sulfur clusters into SDHB, the iron-sulfur protein subunit of succinate dehydrogenase that is involved in complex II of the mitochondrial electron transport chain (PubMed:26749241). Recruited to SDHB by interaction with SDHAF1 which first binds SDHB and then recruits the iron-sulfur transfer complex formed by HSC20, HSPA9 and ISCU through direct binding to HSC20 (PubMed:26749241). Also mediates complex formation between components of the cytosolic iron-sulfur biogenesis pathway and the CIA targeting complex composed of CIAO1, DIPK1B/FAM69B and MMS19 by binding directly to the scaffold protein ISCU and to CIAO1 (PubMed:29309586). This facilitates iron-sulfur cluster insertion into a number of cytoplasmic and nuclear proteins including POLD1, ELP3, DPYD and PPAT (PubMed:29309586).

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HSCB Gene

Genomics for HSCB Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for HSCB Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HSCB on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HSCB

Top Transcription factor binding sites by QIAGEN in the HSCB gene promoter:
  • CUTL1
  • IRF-7A
  • p300
  • Pax-4a
  • SREBP-1a
  • SREBP-1b
  • STAT3

Genomic Locations for HSCB Gene

Latest Assembly
chr22:28,741,992-28,757,515
(GRCh38/hg38)
Size:
15,524 bases
Orientation:
Plus strand

Previous Assembly
chr22:29,138,020-29,153,498
(GRCh37/hg19 by Entrez Gene)
Size:
15,479 bases
Orientation:
Plus strand

chr22:29,138,019-29,153,503
(GRCh37/hg19 by Ensembl)
Size:
15,485 bases
Orientation:
Plus strand

Genomic View for HSCB Gene

Genes around HSCB on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HSCB Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HSCB Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HSCB Gene

Proteins for HSCB Gene

  • Protein details for HSCB Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8IWL3-HSC20_HUMAN
    Recommended name:
    Iron-sulfur cluster co-chaperone protein HscB
    Protein Accession:
    Q8IWL3
    Secondary Accessions:
    • Q9BWS7

    Protein attributes for HSCB Gene

    Size:
    235 amino acids
    Molecular mass:
    27422 Da
    Quaternary structure:
    • Self-interacts (PubMed:29309586). Interacts with ISCU and HSPA9 to form an iron-sulfur transfer complex (PubMed:20668094). Interacts with SDHAF1 (via the first LYR motif); the interaction recruits the iron-sulfur transfer complex composed of HSC20, HSPA9 and ISCU and mediates the incorporation of iron-sulfur clusters into SDHB which also interacts with HSC20 (PubMed:26749241). Interacts with the cytoplasmic form of ISCU and with CIA complex member CIAO1 (via LYR motif) (PubMed:29309586).

    Three dimensional structures from OCA and Proteopedia for HSCB Gene

neXtProt entry for HSCB Gene

Post-translational modifications for HSCB Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for HSCB Gene

Domains & Families for HSCB Gene

Gene Families for HSCB Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for HSCB Gene

InterPro:
Blocks:
  • HSCB oligomerisation, C-terminal
ProtoNet:

Suggested Antigen Peptide Sequences for HSCB Gene

GenScript: Design optimal peptide antigens:
  • Hsc20 (HSC20_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8IWL3

UniProtKB/Swiss-Prot:

HSC20_HUMAN :
  • Belongs to the HscB family.
Family:
  • Belongs to the HscB family.
genes like me logo Genes that share domains with HSCB: view

Function for HSCB Gene

Molecular function for HSCB Gene

UniProtKB/Swiss-Prot Function:
Acts as a co-chaperone in iron-sulfur cluster assembly in both mitochondria and the cytoplasm (PubMed:20668094, PubMed:29309586). Required for incorporation of iron-sulfur clusters into SDHB, the iron-sulfur protein subunit of succinate dehydrogenase that is involved in complex II of the mitochondrial electron transport chain (PubMed:26749241). Recruited to SDHB by interaction with SDHAF1 which first binds SDHB and then recruits the iron-sulfur transfer complex formed by HSC20, HSPA9 and ISCU through direct binding to HSC20 (PubMed:26749241). Also mediates complex formation between components of the cytosolic iron-sulfur biogenesis pathway and the CIA targeting complex composed of CIAO1, DIPK1B/FAM69B and MMS19 by binding directly to the scaffold protein ISCU and to CIAO1 (PubMed:29309586). This facilitates iron-sulfur cluster insertion into a number of cytoplasmic and nuclear proteins including POLD1, ELP3, DPYD and PPAT (PubMed:29309586).

Phenotypes From GWAS Catalog for HSCB Gene

Gene Ontology (GO) - Molecular Function for HSCB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001671 ATPase activator activity IEA --
GO:0003674 molecular_function ND --
GO:0005515 protein binding IPI 20668094
GO:0042802 identical protein binding IPI 24606901
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with HSCB: view
genes like me logo Genes that share phenotypes with HSCB: view

miRNA for HSCB Gene

miRTarBase miRNAs that target HSCB

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HSCB

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for HSCB Gene

Localization for HSCB Gene

Subcellular locations from UniProtKB/Swiss-Prot for HSCB Gene

[Iron-sulfur cluster co-chaperone protein HscB, cytoplasmic]: Cytoplasm.
[Iron-sulfur cluster co-chaperone protein HscB, mitochondrial]: Mitochondrion.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HSCB gene
Compartment Confidence
mitochondrion 5
cytosol 5
nucleus 4
plasma membrane 3
cytoskeleton 2
extracellular 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Mitochondria (3)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for HSCB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IEA,IDA 20668094
GO:0005739 mitochondrion IDA,TAS 12938016
GO:0005829 cytosol IDA --
genes like me logo Genes that share ontologies with HSCB: view

Pathways & Interactions for HSCB Gene

PathCards logo

SuperPathways for HSCB Gene

genes like me logo Genes that share pathways with HSCB: view

Pathways by source for HSCB Gene

2 Reactome pathways for HSCB Gene

UniProtKB/Swiss-Prot Q8IWL3-HSC20_HUMAN

  • Pathway: Cofactor biosynthesis; iron-sulfur cluster biosynthesis.

Gene Ontology (GO) - Biological Process for HSCB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016226 iron-sulfur cluster assembly IMP 20668094
GO:0032781 positive regulation of ATPase activity IEA --
GO:0044571 [2Fe-2S] cluster assembly IBA 21873635
GO:0051259 protein complex oligomerization IEA --
GO:0097428 protein maturation by iron-sulfur cluster transfer IEA --
genes like me logo Genes that share ontologies with HSCB: view

No data available for SIGNOR curated interactions for HSCB Gene

Drugs & Compounds for HSCB Gene

(1) Drugs for HSCB Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Fe2+ Experimental Pharma 0
genes like me logo Genes that share compounds with HSCB: view

Transcripts for HSCB Gene

mRNA/cDNA for HSCB Gene

5 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HSCB

Alternative Splicing Database (ASD) splice patterns (SP) for HSCB Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b
SP1: -
SP2:
SP3:

Relevant External Links for HSCB Gene

GeneLoc Exon Structure for
HSCB

Expression for HSCB Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HSCB Gene

Protein differential expression in normal tissues from HIPED for HSCB Gene

This gene is overexpressed in Heart (27.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for HSCB Gene



Protein tissue co-expression partners for HSCB Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HSCB

SOURCE GeneReport for Unigene cluster for HSCB Gene:

Hs.632780

mRNA Expression by UniProt/SwissProt for HSCB Gene:

Q8IWL3-HSC20_HUMAN
Tissue specificity: Expressed in lung, brain, stomach, spleen, ovary, testis, liver, muscle and heart.

Evidence on tissue expression from TISSUES for HSCB Gene

  • Eye(4.1)
genes like me logo Genes that share expression patterns with HSCB: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for HSCB Gene

Orthologs for HSCB Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for HSCB Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia HSCB 30 31
  • 99.43 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia HSCB 30 31
  • 88.79 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia HSCB 30 31
  • 87.52 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Hscb 30 17 31
  • 80.48 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Hscb 30
  • 79.91 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia HSCB 31
  • 71 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia HSCB 31
  • 63 (a)
OneToOne
Chicken
(Gallus gallus)
Aves HSCB 30 31
  • 60.21 (n)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia hscb 30
  • 56.87 (n)
Zebrafish
(Danio rerio)
Actinopterygii si:ch211-207k7.4 30
  • 54.53 (n)
HSCB 31
  • 33 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP004722 30
  • 50.41 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta l(3)72Do 30 31
  • 44.17 (n)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea dnj-15 30 31
  • 46.35 (n)
OneToOne
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes JAC1 31 33
  • 24 (a)
OneToOne
Thale Cress
(Arabidopsis thaliana)
eudicotyledons AT5G06410 30
  • 49.46 (n)
Rice
(Oryza sativa)
Liliopsida Os12g0456200 30
  • 46.81 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.1107 31
  • 29 (a)
OneToOne
Species where no ortholog for HSCB was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for HSCB Gene

ENSEMBL:
Gene Tree for HSCB (if available)
TreeFam:
Gene Tree for HSCB (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HSCB: view image

Paralogs for HSCB Gene

No data available for Paralogs for HSCB Gene

Variants for HSCB Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HSCB Gene

SNP ID Clinical significance and condition Chr 22 pos Variation AA Info Type
rs1269754581 Likely Benign: not provided 28,742,059(+) C/T
NM_172002.5(HSCB):c.-37C>T
NON_CODING_TRANSCRIPT_VARIANT,FIVE_PRIME_UTR
rs187164042 Likely Benign: Familial cancer of breast 28,742,014(+) G/A
NC_000022.11:g.28742014G>A
rs200681712 Likely Benign: not provided 28,742,108(+) A/G
NM_172002.5(HSCB):c.13A>G (p.Arg5Gly)
MISSENSE_VARIANT,NON_CODING_TRANSCRIPT
rs17884212 - p.Ile163Met
rs17886090 - p.Tyr73Cys

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for HSCB Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for HSCB Gene

Variant ID Type Subtype PubMed ID
esv3647518 CNV loss 21293372
esv3647519 CNV loss 21293372
esv3647520 CNV loss 21293372
nsv1064079 CNV gain 25217958
nsv834169 CNV loss 17160897
nsv9895 CNV gain+loss 18304495

Variation tolerance for HSCB Gene

Residual Variation Intolerance Score: 49.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.82; 47.75% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HSCB Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
HSCB

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HSCB Gene

Disorders for HSCB Gene

MalaCards: The human disease database

(7) MalaCards diseases for HSCB Gene - From: COP and GCD

- elite association - COSMIC cancer census association via MalaCards
Search HSCB in MalaCards View complete list of genes associated with diseases

Additional Disease Information for HSCB

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with HSCB: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HSCB Gene

Publications for HSCB Gene

  1. Identification of a novel candidate gene in the iron-sulfur pathway implicated in ataxia-susceptibility: human gene encoding HscB, a J-type co-chaperone. (PMID: 12938016) Sun G … Vickery LE (Journal of human genetics 2003) 2 3 4 23
  2. Cytosolic HSC20 integrates de novo iron-sulfur cluster biogenesis with the CIAO1-mediated transfer to recipients. (PMID: 29309586) Kim KS … Rouault TA (Human molecular genetics 2018) 3 4
  3. Disease-Causing SDHAF1 Mutations Impair Transfer of Fe-S Clusters to SDHB. (PMID: 26749241) Maio N … Rouault TA (Cell metabolism 2016) 3 4
  4. Characterization of the human HSC20, an unusual DnaJ type III protein, involved in iron-sulfur cluster biogenesis. (PMID: 20668094) Uhrigshardt H … Rouault TA (Human molecular genetics 2010) 3 4
  5. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 41

Products for HSCB Gene

Sources for HSCB Gene