COMMD5: A Key Regulator of Copper Homeostasis and NF-κB Signaling
Comprehensive genomic and proteomic analysis of COMMD5, a member of the COMMD protein family involved in copper metabolism, inflammation, and cancer.
Gene Information Card
| Symbol | COMMD5 |
|---|---|
| Full Name | COMM domain containing 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q24.3 |
| NCBI Gene ID | 28991 ncbi.nlm.nih.gov/gene/28991 |
| Ensembl ID | ENSG00000147677 |
| UniProt ID | Q9H0A9 |
| OMIM ID | 615146 |
| HGNC ID | 24241 |
| Aliases | HT001, UPF0489 protein C8orf38, C8orf38 |
Description
COMMD5 (COMM domain containing 5) is a protein-coding gene located on chromosome 8q24.3. It belongs to the COMMD family, characterized by a conserved COMM domain. COMMD5 is involved in copper homeostasis, NF-κB signaling, and cellular stress responses. It interacts with the copper-transporting ATPase ATP7B and modulates its trafficking. COMMD5 also negatively regulates NF-κB activation by promoting ubiquitination and degradation of the NF-κB subunit RelA. Altered expression of COMMD5 has been implicated in hepatocellular carcinoma and other cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | COMMD5 expression is downregulated in HCC; loss of COMMD5 may promote NF-κB activation and tumor progression. | PMID: 23431129 |
| Copper metabolism disorders | COMMD5 interacts with ATP7B; dysregulation may contribute to copper accumulation. | PMID: 19160496 |
| Inflammatory diseases | COMMD5 negatively regulates NF-κB; reduced expression may enhance inflammation. | PMID: 19160496 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Brain | 5.1 | Low |
| Heart | 4.2 | Low |
| Lung | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line |
| HEK293 | 10.1 | Embryonic kidney cells |
| HeLa | 7.4 | Cervical cancer cells |
| A549 | 6.0 | Lung carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.337C>T (p.Arg113Trp) | Missense | 0.01% (gnomAD) | Unknown functional impact |
| c.454G>A (p.Gly152Ser) | Missense | 0.005% (gnomAD) | Unknown functional impact |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in COMMD5.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • copper ion binding (GO:0005507) | • positive regulation of I-kappaB kinase/NF-kappaB signaling (GO:0043123) |
| • metal ion binding (GO:0046872) | • cytoplasm (GO:0005737) |
| • nucleus (GO:0005634) |
Pathways
• Copper homeostasis (Reactome: R-HSA-936837)
• NF-kappaB signaling (KEGG: hsa04064)
Protein Summary
COMMD5 is a 223-amino acid protein containing a COMM domain. It localizes to the cytoplasm and nucleus. The protein binds copper ions and interacts with ATP7B, influencing copper transport. It also regulates NF-κB signaling by promoting RelA ubiquitination and degradation. COMMD5 is expressed in multiple tissues, with highest levels in liver and kidney. Its downregulation in hepatocellular carcinoma suggests a tumor suppressor role.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| COMMD5 Knockout HEK293 Cell Line | EDJ-KQ8958 | Human | 28991 | Details Get a Quote |
| COMMD5 Knockout A-549 Cell Line | EDJ-KQ35344 | Human | 28991 | Details Get a Quote |
| COMMD5 Knockout HCT 116 Cell Line | EDJ-KQ35345 | Human | 28991 | Details Get a Quote |
| COMMD5 Knockout HeLa Cell Line | EDJ-KQ35346 | Human | 28991 | Details Get a Quote |
