RNF5
protein-codingring finger protein 5, the group of MicroRNA protein coding host genes|Ring finger proteins
Gene summary
The protein encoded by this gene contains a RING finger, which is a motif known to be involved in protein-protein interactions. This protein is a membrane-bound ubiquitin ligase. It can regulate cell motility by targeting paxillin ubiquitination and altering the distribution and localization of paxillin in cytoplasm and cell focal adhesions. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.4 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 RNF5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006913.4. 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 | 0 | |||||
| missense | 7 | 1 | 8 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 7 | 1 | 0 | 8 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_008844.1 | 6 | MANE Select | |
| Ensembl | ENSP00000364235.3 | 6 | MANE Select | |
| Ensembl | ENSP00000546480.1 | 6 | Standard | |
| Ensembl | ENSP00000546480.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
- Disorders of transmembrane transporters
- Disease
- Defective CFTR causes cystic fibrosis
- ER Quality Control Compartment (ERQC)
Biological Process
- ubiquitin-dependent protein catabolic process
- response to bacterium
- negative regulation of autophagy
- ubiquitin-dependent ERAD pathway
- protein destabilization
Molecular Function
- ubiquitin-protein transferase activity
- protein binding
- zinc ion binding
- identical protein binding
- ubiquitin-like protein conjugating enzyme binding
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- integral component of membrane
- mitochondrial membrane
- Derlin-1 retrotranslocation complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000375094
- Coding exons
- 6
- Length
- 5800
- Individuals with no LoFs
- 125730
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125748
- p
- 0.0000716
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.790 | 82 | 105 | 0.783 | 0.00000599 | 1164 |
| Missense (PolyPhen) | 20 | 29.147 | 0.68617 | 299 | ||
| Synonymous | 0.0349 | 40 | 40.3 | 0.993 | 0.00000214 | 355 |
| Loss of Function | 0.797 | 8 | 10.8 | 0.739 | 5.52e-7 | 116 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000080 | 0.000079 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Has E2-dependent E3 ubiquitin-protein ligase activity. May function together with E2 ubiquitin-conjugating enzymes UBE2D1/UBCH5A and UBE2D2/UBC4. Mediates ubiquitination of PXN/paxillin and Salmonella type III secreted protein sopA. May be involved in regulation of cell motility and localization of PXN/paxillin. Mediates the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD; the ubiquitination appears to involve E2 ubiquitin-conjugating enzyme UBE2N. Mediates the 'Lys-48'-linked polyubiquitination of TMEM173 at 'Lys-150' leading to its proteasomal degradation; the ubiquitination occurs in mitochondria after viral transfection and regulates antiviral responses. {ECO:0000269|PubMed:11329381, ECO:0000269|PubMed:12861019, ECO:0000269|PubMed:16176924, ECO:0000269|PubMed:19269966, ECO:0000269|PubMed:19285439}.;
Intolerance Scores
- LoFtool
- 0.519
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 49.39
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.956
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |