MARCHF5
protein-codingmembrane associated ring-CH-type finger 5, the group of Ring finger proteins|Membrane associated ring-CH-type fingers
Gene summary
MARCH5 is a ubiquitin ligase of the mitochondrial outer membrane that plays a role in the control of mitochondrial morphology by regulating mitofusin-2 (MFN2; MIM 608507) and DRP1 (DNM1L; MIM 603850) (Nakamura et al., 2006 [PubMed 16936636]).[supplied by OMIM, Mar 2008]
- RNF153
- MARCH5
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~62.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MARCHF5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017824.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 13 | 13 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 17 | 0 | 0 | 17 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060294.1 | 6 | MANE Select | |
| Ensembl | ENSP00000351813.2 | 6 | MANE Select | |
| Ensembl | ENSP00000554951.1 | 6 | Standard | |
| Ensembl | ENSP00000554951.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- protein polyubiquitination
- protein autoubiquitination
- protein localization to mitochondrion
- regulation of mitochondrial fission
- positive regulation of mitochondrial fission
Molecular Function
- ubiquitin-protein transferase activity
- protein binding
- zinc ion binding
- GTPase binding
Cellular Component
- mitochondrion
- mitochondrial outer membrane
- endoplasmic reticulum
- endoplasmic reticulum membrane
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000358935
- Coding exons
- 6
- Length
- 62802
- Individuals with no LoFs
- 125724
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125727
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.65 | 59 | 150 | 0.393 | 0.00000750 | 1800 |
| Missense (PolyPhen) | 4 | 40.473 | 0.098831 | 447 | ||
| Synonymous | -0.0202 | 49 | 48.8 | 1.00 | 0.00000244 | 539 |
| Loss of Function | 3.25 | 2 | 16.1 | 0.125 | 9.17e-7 | 172 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000030 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000034 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mitochondrial E3 ubiquitin-protein ligase that plays a crucial role in the control of mitochondrial morphology by acting as a positive regulator of mitochondrial fission. May play a role in the prevention of cell senescence acting as a regulator of mitochondrial quality control. Promotes ubiquitination of FIS1, DNM1L and MFN1. {ECO:0000269|PubMed:16874301, ECO:0000269|PubMed:17606867, ECO:0000269|PubMed:19741096, ECO:0000269|PubMed:20103533}.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- LoFtool
- 0.143
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 42.88
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- N
- Indispensability score
- 0.342
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |