ISCU (Iron-Sulfur Cluster Assembly Enzyme)
Essential mitochondrial scaffold for Fe-S cluster biogenesis; mutations cause ISCU myopathy
Gene Information Card
| Symbol | ISCU |
|---|---|
| Full Name | Iron-Sulfur Cluster Assembly Enzyme |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.11 |
| NCBI Gene ID | 23479 ncbi.nlm.nih.gov/gene/23479 |
| Ensembl ID | ENSG00000136003 |
| UniProt ID | Q9H1K1 |
| OMIM ID | 611911 |
| HGNC ID | 29882 |
| Aliases | HML, NIFUN, NIFUN, ISCU1, ISCU2 |
Description
The ISCU gene encodes a mitochondrial scaffold protein essential for the assembly of iron-sulfur (Fe-S) clusters, which are cofactors required for the function of numerous mitochondrial and cytosolic proteins involved in electron transport, DNA repair, and metabolism. Mutations in ISCU cause a rare autosomal recessive myopathy with severe exercise intolerance, lactic acidosis, and deficiency of Fe-S cluster-containing enzymes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Myopathy with lactic acidosis (ISCU myopathy) | Loss-of-function mutations impair Fe-S cluster assembly, leading to deficiency of mitochondrial respiratory chain complexes I, II, and III and aconitase. | ClinVar, OMIM #611911 |
| Multiple mitochondrial dysfunctions syndrome (rare) | Severe biallelic variants disrupt Fe-S cluster biogenesis, causing multisystem failure. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 28.5 | High |
| Heart | 22.3 | High |
| Liver | 18.7 | Medium |
| Brain | 15.2 | Medium |
| Kidney | 14.8 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 32.1 | High expression |
| K-562 | 27.4 | High expression |
| HepG2 | 25.6 | High expression |
| SH-SY5Y | 20.3 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.149G>A (p.Gly50Glu) | Missense | Common in Finnish population | Loss of function; reduced Fe-S cluster assembly |
| c.112A>G (p.Arg38Gly) | Missense | Rare | Impaired protein stability and function |
| c.1A>G (p.Met1Val) | Start loss | Rare | Complete loss of translation |
Mutation functional classification
Loss of Function (LOF)
Most ISCU mutations are loss-of-function, reducing Fe-S cluster assembly and causing mitochondrial enzyme deficiencies.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations described; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Iron-sulfur cluster assembly (mitochondrial) – Reactome R-HSA-1369007
• Mitochondrial biogenesis – KEGG hsa04122
• Metabolism of iron and heme – Reactome R-HSA-917937
Protein Summary
ISCU is a 167-amino acid mitochondrial scaffold protein that binds iron and sulfur atoms to form transient Fe-S clusters, which are then transferred to apoproteins. It exists in two isoforms: ISCU1 (cytosolic) and ISCU2 (mitochondrial). The protein contains a conserved LYR motif and interacts with NFS1, ISD11, and frataxin to form the core Fe-S cluster assembly complex. Deficiency leads to impaired oxidative phosphorylation and energy metabolism.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID |
|---|
