RANBP9
protein-codingRAN binding protein 9, the group of CTLH complex
Gene summary
This gene encodes a protein that binds RAN, a small GTP binding protein belonging to the RAS superfamily that is essential for the translocation of RNA and proteins through the nuclear pore complex. The protein encoded by this gene has also been shown to interact with several other proteins, including met proto-oncogene, homeodomain interacting protein kinase 2, androgen receptor, and cyclin-dependent kinase 11. [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 ~90.3 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 RANBP9 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005493.3. 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 | 2 | 3 | |||
| missense | 118 | 118 | ||||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 125 | 2 | 0 | 127 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005484.2 | 14 | MANE Select | |
| Ensembl | ENSP00000011619.3 | 14 | MANE Select | |
| Ensembl | ENSP00000610206.1 | 14 | Standard | |
| Ensembl | ENSP00000610206.1 | 14 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ranbp9 | Danio rerio | Structure: Muller cell Quality: absent abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Brain-Derived Neurotrophic Factor (BDNF) signaling pathway
- Developmental Biology
- Signal Transduction
- AndrogenReceptor
- BDNF
Biological Process
- MAPK cascade
- microtubule nucleation
- axon guidance
- protein-containing complex assembly
- negative regulation of ERK1 and ERK2 cascade
Molecular Function
- Ras guanyl-nucleotide exchange factor activity
- protein binding
- Ran GTPase binding
- enzyme binding
Cellular Component
- ubiquitin ligase complex
- nucleus
- cytoplasm
- cytosol
- microtubule associated complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000011619
- Coding exons
- 14
- Length
- 90067
- Individuals with no LoFs
- 118838
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 118839
- p
- 0.00000421
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.49 | 258 | 335 | 0.771 | 0.0000165 | 4683 |
| Missense (PolyPhen) | 103 | 169.01 | 0.60941 | 1989 | ||
| Synonymous | -1.63 | 144 | 121 | 1.19 | 0.00000639 | 1451 |
| Loss of Function | 5.45 | 1 | 36.5 | 0.0274 | 0.00000209 | 430 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000057 | 0.000057 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May act as scaffolding protein, and as adapter protein to couple membrane receptors to intracellular signaling pathways (Probable). Acts as a mediator of cell spreading and actin cytoskeleton rearrangement (PubMed:18710924). Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (PubMed:29911972). May be involved in signaling of ITGB2/LFA- 1 and other integrins (PubMed:14722085). Enhances HGF-MET signaling by recruiting Sos and activating the Ras pathway (PubMed:12147692). Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but not affect estrogen-induced transactivation (PubMed:12361945, PubMed:18222118). Stabilizes TP73 isoform Alpha, probably by inhibiting its ubiquitination, and increases its proapoptotic activity (PubMed:15558019). Inhibits the kinase activity of DYRK1A and DYRK1B. Inhibits FMR1 binding to RNA. {ECO:0000269|PubMed:12147692, ECO:0000269|PubMed:12361945, ECO:0000269|PubMed:14500717, ECO:0000269|PubMed:14722085, ECO:0000269|PubMed:15381419, ECO:0000269|PubMed:15558019, ECO:0000269|PubMed:18222118, ECO:0000269|PubMed:18710924, ECO:0000269|PubMed:29911972, ECO:0000305}.;
Recessive Scores
- pRec
- 0.206
Intolerance Scores
- LoFtool
- 0.0392
- RVIS EVS
- -0.76
- RVIS percentile EVS
- 13.45
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.806
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |