RNF145
protein-codingring finger protein 145, the group of Ring finger proteins
Gene summary
Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in ERAD pathway and proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to be located in endoplasmic reticulum membrane. Predicted to be active in endomembrane system. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~52.6 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 RNF145 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001199383.2. 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 | 4 | 4 | ||||
| missense | 39 | 2 | 41 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 46 | 2 | 0 | 48 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001186312.1 | 10 | MANE Select | |
| Ensembl | ENSP00000409064.2 | 10 | MANE Select | |
| RefSeq | NP_001186309.1 | 11 | Standard | |
| RefSeq | NP_001186310.1 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| rnf145b | Danio rerio | Structure: myeloid cell development Quality: absent abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Molecular Function
- zinc ion binding
- transferase activity
- ubiquitin protein ligase activity
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- endomembrane system
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000518802
- Coding exons
- 11
- Length
- 52645
- Individuals with no LoFs
- 125738
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125743
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.59 | 171 | 364 | 0.470 | 0.0000182 | 4522 |
| Missense (PolyPhen) | 33 | 148.09 | 0.22283 | 1846 | ||
| Synonymous | -0.340 | 141 | 136 | 1.04 | 0.00000689 | 1349 |
| Loss of Function | 4.36 | 4 | 29.6 | 0.135 | 0.00000147 | 374 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000048 | 0.000046 | rare |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin ligase that catalyzes the direct transfer of ubiquitin from E2 ubiquitin-conjugating enzyme to a specific substrate. In response to bacterial infection, negatively regulates the phagocyte oxidative burst by controlling the turnover of the NADPH oxidase complex subunits. Promotes monoubiquitination of CYBA and 'Lys-48'-linked polyubiquitination and degradation of CYBB NADPH oxidase catalytic subunits, both essential for the generation of antimicrobial reactive oxygen species. Involved in the maintenance of cholesterol homeostasis. In response to high sterol concentrations ubiquitinates HMGCR, a rate-limiting enzyme in cholesterol biosynthesis, and targets it for degradation. The interaction with INSIG1 is required for this function. In addition, triggers ubiquitination of SCAP, likely inhibiting its transport to the Golgi apparatus and the subsequent processing/maturation of SREBPF2, ultimately downregulating cholesterol biosynthesis. {ECO:0000250|UniProtKB:Q5SWK7}.;
Intolerance Scores
- LoFtool
- 0.390
- RVIS EVS
- -0.74
- RVIS percentile EVS
- 13.94
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.134
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |