CISD2 Gene - CDGSH Iron Sulfur Domain 2
Essential regulator of mitochondrial function, calcium homeostasis, and aging; associated with Wolfram syndrome 2 and cancer
Gene Information Card
| Symbol | CISD2 |
|---|---|
| Full Name | CDGSH Iron Sulfur Domain 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q24 |
| NCBI Gene ID | 493856 ncbi.nlm.nih.gov/gene/493856 |
| Ensembl ID | ENSG00000174796 |
| UniProt ID | Q8N5K1 |
| OMIM ID | 611507 |
| HGNC ID | 24215 |
| Aliases | ERIS, WFS2, ZCD2, MGC10946 |
Description
CISD2 encodes a mitochondrial membrane protein containing a CDGSH iron-sulfur domain. It is localized to the outer mitochondrial membrane and endoplasmic reticulum (ER) contact sites, where it regulates mitochondrial iron homeostasis, calcium signaling, and autophagy. Loss-of-function mutations cause Wolfram syndrome 2 (WFS2), a neurodegenerative disorder characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. CISD2 is also implicated in aging and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Wolfram syndrome 2 (WFS2) | Loss-of-function mutations in CISD2 disrupt mitochondrial iron-sulfur cluster biogenesis and ER-mitochondria calcium transfer, leading to increased oxidative stress and apoptosis in pancreatic beta cells and neurons. | OMIM #604928; ClinVar; NCBI Gene |
| Breast cancer | CISD2 overexpression promotes tumor cell proliferation and migration via enhanced mitochondrial function and resistance to apoptosis. | COSMIC; PubMed studies |
| Hepatocellular carcinoma | Elevated CISD2 expression correlates with poor prognosis and increased metastatic potential through modulation of mitochondrial dynamics. | COSMIC; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Heart | 8.7 | Medium |
| Liver | 6.5 | Low |
| Brain | 4.2 | Low |
| Pancreas | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression in embryonic kidney cells |
| HepG2 | 9.8 | Moderate expression in liver cancer cells |
| MCF7 | 7.1 | Moderate expression in breast cancer cells |
| SH-SY5Y | 5.4 | Low expression in neuroblastoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.109C>T (p.Arg37Ter) | Nonsense | Reported in WFS2 families | Loss of function; truncated protein |
| c.103G>A (p.Gly35Ser) | Missense | Rare in population databases | Impaired iron-sulfur cluster binding |
| c.200_201del (p.Leu67Profs*12) | Frameshift | Reported in WFS2 families | Loss of function; premature stop |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and missense mutations that disrupt the CDGSH domain or cause protein truncation lead to loss of CISD2 function, resulting in mitochondrial dysfunction and Wolfram syndrome 2.
Gain of Function (GOF)
Not established; overexpression in cancer suggests potential oncogenic gain-of-function, but no activating mutations have been characterized.
Dominant Negative (DN)
Not reported; Wolfram syndrome 2 is autosomal recessive, requiring biallelic loss-of-function mutations.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Mitochondrial iron-sulfur cluster biogenesis
• ER-mitochondria contact site signaling
• Autophagy regulation
• Apoptosis
Protein Summary
CISD2 is a 135-amino acid protein (UniProt Q8N5K1) with a single transmembrane domain and a CDGSH iron-sulfur domain. It forms homodimers and binds a [2Fe-2S] cluster essential for its function. The protein localizes to mitochondria-associated ER membranes (MAMs), where it modulates calcium flux and mitochondrial dynamics. CISD2 deficiency leads to ER stress, impaired autophagy, and increased sensitivity to oxidative damage.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CISD2 Knockout HEK293 Cell Line | EDJ-KQ11894 | Human | 493856 | Details Get a Quote |
| CISD2 Knockout A-549 Cell Line | EDJ-KQ40347 | Human | 493856 | Details Get a Quote |
| CISD2 Knockout HCT 116 Cell Line | EDJ-KQ40348 | Human | 493856 | Details Get a Quote |
| CISD2 Knockout HeLa Cell Line | EDJ-KQ40349 | Human | 493856 | Details Get a Quote |
