NFU1 Iron-Sulfur Cluster Scaffold Gene
Essential for mitochondrial iron-sulfur cluster biogenesis; mutations cause multiple mitochondrial dysfunctions syndrome
Gene Information Card
| Symbol | NFU1 |
|---|---|
| Full Name | NFU1 iron-sulfur cluster scaffold |
| Gene Type | protein-coding |
| Chromosomal Location | 2p13.3 |
| NCBI Gene ID | 27247 ncbi.nlm.nih.gov/gene/27247 |
| Ensembl ID | ENSG00000169592 |
| UniProt ID | Q9UMS0 |
| OMIM ID | 608100 |
| HGNC ID | 16290 |
| Aliases | HIRIP5, NIFUN, NFU1A, NFU1B |
Description
The NFU1 gene encodes a mitochondrial protein that functions as a scaffold for iron-sulfur (Fe-S) cluster assembly. It is essential for the maturation of mitochondrial Fe-S proteins, including components of the respiratory chain and other metabolic pathways. Mutations in NFU1 cause multiple mitochondrial dysfunctions syndrome type 1 (MMDS1), characterized by severe neurological and metabolic impairment.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Multiple mitochondrial dysfunctions syndrome 1 (MMDS1) | Impaired Fe-S cluster biogenesis leads to deficiency of mitochondrial respiratory chain complexes I, II, and III, as well as lipoic acid synthase (LIAS) dysfunction. | OMIM #605711; ClinVar pathogenic variants |
| Leigh syndrome | Secondary mitochondrial dysfunction due to NFU1 mutations may present with Leigh-like neuropathology. | Case reports in ClinVar and literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Heart | 10.3 | Medium |
| Skeletal Muscle | 8.7 | Medium |
| Brain | 6.2 | Low |
| Kidney | 7.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.2 | Hepatocellular carcinoma cell line |
| K-562 | 9.8 | Myelogenous leukemia cell line |
| HeLa | 7.5 | Cervical adenocarcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.545G>A (p.Arg182Gln) | Missense | Reported in MMDS1 patients | Reduced Fe-S cluster assembly activity |
| c.622C>T (p.Arg208Trp) | Missense | Reported in MMDS1 patients | Impaired protein stability and function |
| c.776T>C (p.Leu259Pro) | Missense | Rare | Disrupts scaffold function |
Mutation functional classification
Loss of Function (LOF)
Most NFU1 missense mutations reduce or abolish Fe-S cluster scaffold activity, leading to mitochondrial dysfunction.
Gain of Function (GOF)
No evidence of gain-of-function mutations.
Dominant Negative (DN)
Not reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • iron ion binding (GO:0005506) | • cellular iron ion homeostasis (GO:0006879) |
| • iron-sulfur cluster assembly (GO:0016226) | • mitochondrion (GO:0005739) |
| • iron-sulfur cluster binding (GO:0051536) |
Pathways
• Mitochondrial iron-sulfur cluster biogenesis (Reactome: R-HSA-1369007)
• Respiratory electron transport (Reactome: R-HSA-611105)
Protein Summary
NFU1 is a mitochondrial scaffold protein critical for the assembly and transfer of iron-sulfur clusters to target apoproteins. It contains a conserved NifU-like domain and interacts with other components of the Fe-S cluster machinery. Loss of NFU1 function disrupts mitochondrial respiration and lipoic acid metabolism, leading to severe multisystem disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NFU1 Knockout HEK293 Cell Line | EDJ-KQ8729 | Human | 27247 | Details Get a Quote |
| NFU1 Knockout HCT 116 Cell Line | EDJ-KQ34971 | Human | 27247 | Details Get a Quote |
| NFU1 Knockout HeLa Cell Line | EDJ-KQ34972 | Human | 27247 | Details Get a Quote |
| NFU1 Knockout A-549 Cell Line | EDJ-KQ33703 | Human | 27247 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
