IPO8
protein-codingimportin 8, the group of Importins
Gene summary
The importin-alpha/beta complex and the GTPase Ran mediate nuclear import of proteins with a classical nuclear localization signal. The protein encoded by this gene is a member of a class of approximately 20 potential Ran targets that share a sequence motif related to the Ran-binding site of importin-beta. This protein binds to the nuclear pore complex and, along with RanGTP and RANBP1, inhibits the GAP stimulation of the Ran GTPase. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]
- RANBP8
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~66.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0859177
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0859177
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0859177
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Pulmonary
Intervention: Cardiovascular
Rationale: Among ohther findings, the condition can include increased risk of aneurysms and other cardiovascular anomalies, and awareness may enable surveillance and early interventions
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IPO8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006390.4. 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 | 16 | 17 | |||
| missense | 3 | 119 | 5 | 127 | ||
| nonsense | 5 | 5 | 10 | |||
| start loss | 0 | |||||
| frameshift | 7 | 2 | 9 | |||
| splice donor/acceptor (+/-2bp) | 1 | 3 | 6 | 10 | ||
| Total | 13 | 13 | 126 | 21 | 0 | 173 |
Highest pathogenic variant AF is 0.00000867623
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006381.2 | 25 | MANE Select | |
| Ensembl | ENSP00000256079.4 | 25 | MANE Select | |
| RefSeq | NP_001177924.1 | 21 | Standard | |
| Ensembl | ENSP00000444050.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gene expression (Transcription)
- Transcriptional regulation by small RNAs
- Gene Silencing by RNA
Biological Process
- protein import into nucleus
- signal transduction
- regulation of gene silencing by miRNA
Molecular Function
- protein binding
- Ran GTPase binding
- protein transporter activity
Cellular Component
- nuclear envelope
- nucleoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000256079
- Coding exons
- 25
- Length
- 66999
- Individuals with no LoFs
- 125717
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 31
- Defined
- 125748
- p
- 0.000123
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.12 | 408 | 547 | 0.745 | 0.0000274 | 6855 |
| Missense (PolyPhen) | 50 | 110.02 | 0.45446 | 1374 | ||
| Synonymous | -0.316 | 195 | 189 | 1.03 | 0.00000940 | 1884 |
| Loss of Function | 5.71 | 15 | 64.5 | 0.232 | 0.00000354 | 729 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.000088 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00018 | 0.00018 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Seems to function in nuclear protein import, either by acting as autonomous nuclear transport receptor or as an adapter- like protein in association with the importin-beta subunit KPNB1. Acting autonomously, is thought to serve itself as receptor for nuclear localization signals (NLS) and to promote translocation of import substrates through the nuclear pore complex (NPC) by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. In vitro mediates the nuclear import of SRP19. {ECO:0000269|PubMed:11682607, ECO:0000269|PubMed:9214382}.;
Recessive Scores
- pRec
- 0.175
Intolerance Scores
- LoFtool
- 0.677
- RVIS EVS
- -0.91
- RVIS percentile EVS
- 10.07
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.808
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |