RNF185
protein-codingring finger protein 185, the group of Ring finger proteins
Gene summary
Enables ubiquitin binding activity; ubiquitin protein ligase activity; and ubiquitin-like protein conjugating enzyme binding activity. Involved in several processes, including positive regulation of ERAD pathway; protein catabolic process; and protein ubiquitination. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~46.8 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 RNF185 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152267.4. 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 | 1 | 1 | ||||
| missense | 19 | 19 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 21 | 0 | 1 | 22 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689480.2 | 6 | MANE Select | |
| Ensembl | ENSP00000320508.5 | 6 | MANE Select | |
| RefSeq | NP_001129297.1 | 4 | Standard | |
| Ensembl | ENSP00000266252.7 | 4 | 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
- autophagy
- ubiquitin-dependent ERAD pathway
- ERAD pathway
- protein autoubiquitination
Molecular Function
- protein binding
- ubiquitin-like protein conjugating enzyme binding
- metal ion binding
- ubiquitin protein ligase activity
Cellular Component
- mitochondrial outer membrane
- endoplasmic reticulum
- endoplasmic reticulum membrane
- integral component of membrane
- Derlin-1 retrotranslocation complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000326132
- Coding exons
- 6
- Length
- 46838
- Individuals with no LoFs
- 125741
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125748
- p
- 0.0000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.05 | 81 | 112 | 0.720 | 0.00000600 | 1250 |
| Missense (PolyPhen) | 15 | 35.77 | 0.41935 | 396 | ||
| Synonymous | -0.374 | 47 | 43.8 | 1.07 | 0.00000256 | 374 |
| Loss of Function | 2.18 | 3 | 10.7 | 0.280 | 5.39e-7 | 117 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase that regulates selective mitochondrial autophagy by mediating 'Lys-63'-linked polyubiquitination of BNIP1 (PubMed:21931693). Acts in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which targets misfolded proteins that accumulate in the endoplasmic reticulum (ER) for ubiquitination and subsequent proteasome-mediated degradation (PubMed:27485036). Protects cells from ER stress-induced apoptosis (PubMed:27485036). Responsible for the cotranslational ubiquitination and degradation of CFTR in the ERAD pathway (PubMed:24019521). Preferentially associates with the E2 enzymes UBE2J1 and UBE2J2 (PubMed:24019521). {ECO:0000269|PubMed:21931693, ECO:0000269|PubMed:24019521, ECO:0000269|PubMed:27485036}.;
Intolerance Scores
- LoFtool
- 0.136
- RVIS EVS
- -0.01
- RVIS percentile EVS
- 53.19
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.868
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |