BOLA3: A Key Player in Iron-Sulfur Cluster Biogenesis and Mitochondrial Function
Comprehensive gene card for BOLA3, including genomic data, expression, disease associations, and functional classification.
Gene Information Card
| Symbol | BOLA3 |
|---|---|
| Full Name | bolA family member 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 2p13.1 |
| NCBI Gene ID | 11223 ncbi.nlm.nih.gov/gene/11223 |
| Ensembl ID | ENSG00000163170 |
| UniProt ID | Q9NP59 |
| OMIM ID | 613183 |
| HGNC ID | 19855 |
| Aliases | FLJ20489, MGC2650, IscA3, MMDS2 |
Description
BOLA3 encodes a member of the BolA-like protein family, which is involved in iron-sulfur (Fe-S) cluster biogenesis. The protein localizes to mitochondria and interacts with NFU1 and other components of the Fe-S cluster assembly machinery. BOLA3 is essential for the maturation of mitochondrial Fe-S proteins, including subunits of respiratory chain complexes I and II. Mutations in BOLA3 cause multiple mitochondrial dysfunctions syndrome type 2 (MMDS2), a severe neurodegenerative disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Multiple mitochondrial dysfunctions syndrome type 2 (MMDS2) | Loss-of-function mutations in BOLA3 impair Fe-S cluster assembly, leading to deficiency of respiratory chain complexes I and II and lipoic acid-dependent enzymes. | OMIM #614299; ClinVar; PMID: 21841772 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Skeletal muscle | 10.8 | Medium |
| Liver | 8.2 | Low |
| Brain | 6.4 | Low |
| Kidney | 7.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 9.3 | Embryonic kidney cells |
| HeLa | 7.8 | Cervical carcinoma |
| HepG2 | 6.5 | Hepatocellular carcinoma |
| SH-SY5Y | 5.2 | Neuroblastoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.200A>G (p.Asn67Ser) | Missense | Rare (found in MMDS2 families) | Loss of function; disrupts Fe-S cluster binding |
| c.136C>T (p.Arg46Trp) | Missense | Rare (found in MMDS2 families) | Loss of function; impairs protein stability |
| c.94C>T (p.Arg32*) | Nonsense | Rare | Loss of function; premature truncation |
Mutation functional classification
Loss of Function (LOF)
All reported pathogenic BOLA3 mutations are loss-of-function, leading to impaired Fe-S cluster biogenesis and mitochondrial dysfunction.
Gain of Function (GOF)
No gain-of-function mutations have been reported for BOLA3.
Dominant Negative (DN)
No dominant-negative mutations have been described; inheritance 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 (R-HSA-1362409)
• Respiratory electron transport (R-HSA-611105)
Protein Summary
BOLA3 is a small mitochondrial protein (approximately 10 kDa) that belongs to the BolA family. It functions as a scaffold or carrier in the late stages of Fe-S cluster assembly, cooperating with NFU1 and ISCA proteins. The protein contains a conserved CxxC motif critical for iron-sulfur cluster coordination. Defects in BOLA3 lead to accumulation of mitochondrial iron and severe respiratory chain deficiency.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BOLA3 Knockout HEK293 Cell Line | EDJ-KQ12557 | Human | 388962 | Details Get a Quote |
| BOLA3 Knockout A-549 Cell Line | EDJ-KQ41570 | Human | 388962 | Details Get a Quote |
| BOLA3 Knockout HCT 116 Cell Line | EDJ-KQ41571 | Human | 388962 | Details Get a Quote |
| BOLA3 Knockout HeLa Cell Line | EDJ-KQ41572 | Human | 388962 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
