ISCA2: Iron-Sulfur Cluster Assembly 2
Mitochondrial Fe-S Cluster Biogenesis and Neurological Disorders
Gene Information Card
| Symbol | ISCA2 |
|---|---|
| Full Name | Iron-Sulfur Cluster Assembly 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q24.3 |
| NCBI Gene ID | 122961 ncbi.nlm.nih.gov/gene/122961 |
| Ensembl ID | ENSG00000100823 |
| UniProt ID | Q86U28 |
| OMIM ID | 615317 |
| HGNC ID | HGNC:28663 |
| Aliases | HBLD2, ISA2, NIFUN |
Description
ISCA2 encodes a mitochondrial protein involved in the biogenesis of iron-sulfur (Fe-S) clusters, specifically acting in the late stage of Fe-S cluster assembly. It functions as a scaffold protein that transfers preformed Fe-S clusters to recipient apoproteins. Mutations in ISCA2 cause multiple mitochondrial dysfunctions syndrome type 4 (MMDS4), characterized by neurodegeneration, leukodystrophy, and early-onset neurological impairment.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Multiple Mitochondrial Dysfunctions Syndrome 4 (MMDS4) | Impaired Fe-S cluster assembly leads to deficiency of mitochondrial respiratory chain complexes I and II and aconitase, causing energy depletion and neurodegeneration. | OMIM #616370; ClinVar; PMID: 25382312 |
| Leukodystrophy | Defective Fe-S cluster biogenesis disrupts myelin maintenance and axonal integrity in the central nervous system. | PMID: 25382312; PMID: 28708303 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 8.2 | Medium |
| Heart | 6.5 | Medium |
| Brain (cerebellum) | 5.1 | Low |
| Skeletal muscle | 4.8 | Low |
| Kidney | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 7.0 | Moderate expression |
| HeLa | 6.2 | Moderate expression |
| SH-SY5Y | 5.5 | Low expression |
| HepG2 | 8.1 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.229G>A (p.Gly77Ser) | Missense | Found in MMDS4 families | Loss of function; impaired Fe-S cluster transfer |
| c.418C>T (p.Arg140*) | Nonsense | Rare | Premature truncation; complete loss of protein function |
| c.1A>G (p.Met1Val) | Start loss | Reported in one family | Loss of translation initiation; null allele |
Mutation functional classification
Loss of Function (LOF)
Yes – missense and nonsense mutations reduce or abolish Fe-S cluster assembly activity, leading to mitochondrial dysfunction.
Gain of Function (GOF)
No evidence.
Dominant Negative (DN)
No evidence; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • mitochondrion (GO:0005739) | • cellular iron ion homeostasis (GO:0006879) |
| • iron-sulfur cluster assembly (GO:0016226) | • iron-sulfur cluster binding (GO:0051536) |
| • iron ion binding (GO:0005506) |
Pathways
• Mitochondrial iron-sulfur cluster biogenesis (Reactome: R-HSA-1369007)
• Metabolism of iron-sulfur clusters (KEGG: hsa04152)
Protein Summary
ISCA2 is a 154-amino acid mitochondrial protein that belongs to the IscA family of Fe-S cluster assembly factors. It forms a homodimer and acts as a scaffold for the assembly and transfer of [2Fe-2S] and [4Fe-4S] clusters to target proteins, including components of the electron transport chain. The protein is essential for cellular respiration and iron homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ISCA2 Knockout HEK293 Cell Line | EDJ-KQ8168 | Human | 122961 | Details Get a Quote |
| ISCA2 Knockout A-549 Cell Line | EDJ-KQ34075 | Human | 122961 | Details Get a Quote |
| ISCA2 Knockout HCT 116 Cell Line | EDJ-KQ34076 | Human | 122961 | Details Get a Quote |
| ISCA2 Knockout HeLa Cell Line | EDJ-KQ34077 | Human | 122961 | Details Get a Quote |
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