HSCB: Iron-Sulfur Cluster Co-Chaperone
Mitochondrial HscB chaperone essential for Fe-S cluster biogenesis and cellular iron homeostasis
Gene Information Card
| Symbol | HSCB |
|---|---|
| Full Name | HscB mitochondrial iron-sulfur cluster co-chaperone |
| Gene Type | protein-coding |
| Chromosomal Location | 22q12.1 |
| NCBI Gene ID | 150274 ncbi.nlm.nih.gov/gene/150274 |
| Ensembl ID | ENSG00000100253 |
| UniProt ID | Q8IWL3 |
| OMIM ID | 608142 |
| HGNC ID | 26569 |
| Aliases | HSC20, DNAJC20, HscB, HSCB1 |
Description
HSCB encodes a mitochondrial J-type co-chaperone that functions with HSPA9 (mortalin) to facilitate the transfer of iron-sulfur (Fe-S) clusters from the scaffold protein ISCU to recipient apoproteins. This process is critical for mitochondrial respiration, DNA repair, and cellular iron sensing. HSCB is essential for Fe-S cluster biogenesis and mutations cause hereditary myopathy with lactic acidosis (MIM #255125).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary myopathy with lactic acidosis (HMERF-like) | Impaired Fe-S cluster transfer leads to mitochondrial dysfunction and energy deficiency | OMIM #255125; PMID: 25716914 |
| Multiple mitochondrial dysfunctions syndrome type 3 | Defective Fe-S cluster assembly disrupts respiratory chain complexes | OMIM #615330; PMID: 25716914 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 12.5 | Medium |
| Heart | 10.8 | Medium |
| Liver | 8.2 | Low |
| Brain | 6.1 | Low |
| Kidney | 7.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 9.3 | Moderate expression |
| HEK293 | 8.7 | Moderate expression |
| K562 | 6.5 | Low expression |
| HepG2 | 7.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.418C>T (p.Arg140Trp) | Missense | Rare | Loss of co-chaperone activity; impaired Fe-S cluster transfer |
| c.1A>G (p.Met1Val) | Start loss | Rare | Complete loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Homozygous or compound heterozygous missense and start-loss mutations reduce or abolish HSCB chaperone activity, leading to Fe-S cluster deficiency.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations described.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding (GO:0005524) | • mitochondrion (GO:0005739) |
| • unfolded protein binding (GO:0051082) | • iron-sulfur cluster assembly (GO:0016226) |
| • heat shock protein binding (GO:0031072) | • protein folding (GO:0006457) |
Pathways
• Iron-sulfur cluster assembly (mitochondrial) - Reactome R-HSA-1369007
• Mitochondrial protein import - Reactome R-HSA-1268020
Protein Summary
HSCB (HscB) is a 235-amino-acid mitochondrial J-domain co-chaperone that binds to the scaffold protein ISCU and recruits HSPA9 to catalyze Fe-S cluster transfer. It contains a conserved J-domain required for interaction with HSPA9 and a C-terminal domain that binds ISCU. The protein is ubiquitously expressed with highest levels in skeletal muscle and heart, reflecting the high demand for Fe-S clusters in oxidative metabolism.
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