MARCHF5 (Membrane Associated Ring-CH-Type Finger 5): A Mitochondrial E3 Ubiquitin Ligase in Health and Disease
Explore the genomic context, expression patterns, and clinical significance of MARCHF5, a key regulator of mitochondrial dynamics and apoptosis.
Gene Information Card
| Symbol | MARCHF5 |
|---|---|
| Full Name | Membrane Associated Ring-CH-Type Finger 5 |
| Gene Type | protein-coding |
| Chromosomal Location | 10q23.32-q23.33 |
| NCBI Gene ID | 54708 ncbi.nlm.nih.gov/gene/54708 |
| Ensembl ID | ENSG00000097046 |
| UniProt ID | Q9NX47 |
| OMIM ID | 616936 |
| HGNC ID | 26077 |
| Aliases | MARCH5, RNF153 |
Description
MARCHF5 encodes a RING-CH-type E3 ubiquitin ligase localized to the mitochondrial outer membrane. It regulates mitochondrial dynamics by ubiquitinating proteins such as mitofusins (MFN1/2) and the mitochondrial fission factor (MFF), thereby controlling fusion/fission balance and mitophagy. MARCHF5 also influences apoptosis by modulating the stability of pro-apoptotic factors. Its expression is ubiquitous, with highest levels in tissues rich in mitochondria. Dysregulation has been implicated in cancer and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered MARCHF5 expression affects mitochondrial dynamics and apoptosis, promoting tumor cell survival and proliferation. | COSMIC: somatic mutations and copy number alterations in multiple cancer types; PubMed studies. |
| Neurodegenerative diseases (e.g., Parkinson's disease) | Impaired MARCHF5-mediated ubiquitination of mitochondrial proteins may disrupt mitophagy, leading to mitochondrial dysfunction. | PubMed: experimental models; ClinVar: rare variants of uncertain significance. |
| Mitochondrial disorders | Mutations affecting MARCHF5 function could impair mitochondrial dynamics, contributing to cellular energy deficits. | ClinVar: variants reported; functional studies in cell lines. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.3 | High |
| Liver | 10.8 | High |
| Skeletal Muscle | 9.5 | Medium |
| Brain | 7.2 | Medium |
| Kidney | 6.8 | Medium |
| Lung | 4.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line; high expression |
| HEK293 | 12.7 | Embryonic kidney; high expression |
| HepG2 | 10.1 | Liver cancer; moderate-high |
| SH-SY5Y | 8.3 | Neuroblastoma; moderate |
| MCF7 | 6.4 | Breast cancer; moderate-low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.286C>T (p.Arg96Cys) | Missense | 0.01% (gnomAD) | Potential loss of function; affects RING domain, may impair ubiquitin ligase activity. |
| c.421A>G (p.Ile141Val) | Missense | 0.03% (gnomAD) | Unknown; located in transmembrane domain, may affect mitochondrial localization. |
| c.532G>A (p.Glu178Lys) | Missense | 0.005% (gnomAD) | Predicted damaging; may disrupt protein-protein interactions. |
Mutation functional classification
Loss of Function (LOF)
Mutations in the RING domain (e.g., p.Arg96Cys) likely reduce E3 ligase activity, leading to impaired ubiquitination of mitochondrial substrates and altered mitochondrial dynamics.
Gain of Function (GOF)
No clear gain-of-function mutations reported; overexpression of wild-type MARCHF5 in cancer may enhance cell survival.
Dominant Negative (DN)
Some missense variants may exert dominant-negative effects by competing with wild-type protein for substrate binding without functional activity.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity | • zinc ion binding |
| • mitochondrial outer membrane | • protein ubiquitination |
| • mitochondrial fission | • mitochondrial fusion |
| • regulation of apoptotic process |
Pathways
• Mitochondrial dynamics (fusion/fission)
• Mitophagy (selective autophagy of mitochondria)
• Apoptosis signaling
Protein Summary
MARCHF5 is a 278-amino acid protein with an N-terminal RING-CH domain facing the cytosol and a C-terminal transmembrane domain anchoring it to the mitochondrial outer membrane. It ubiquitinates substrates like MFN1/2 and MFF, tagging them for proteasomal degradation or altering their activity. This regulates mitochondrial morphology and quality control. MARCHF5 also interacts with the apoptosis regulator BAK, modulating cell death. Its expression is ubiquitous, and dysregulation contributes to disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MARCHF5 Knockout HEK293 Cell Line | EDC90553 | Human | 54708 | Details Get a Quote |
| MARCHF5 Knockout A-549 Cell Line | EDJ-KQ24381 | Human | 54708 | Details Get a Quote |
| MARCHF5 Knockout HCT 116 Cell Line | EDJ-KQ25750 | Human | 54708 | Details Get a Quote |
| MARCHF5 Knockout HeLa Cell Line | EDJ-KQ25751 | Human | 54708 | Details Get a Quote |
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