IPO4
protein-codingimportin 4, the group of Importins|TOG domain containing
Gene summary
Enables nuclear import signal receptor activity and nuclear localization sequence binding activity. Involved in protein import into nucleus. Located in chromatin. Part of protein-containing complex. Is active in cytoplasm and nucleus. [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 ~8.7 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 IPO4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024658.4. 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 | 3 | 3 | 1 | 7 | ||
| missense | 179 | 3 | 2 | 184 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 13 | 13 | ||||
| Total | 0 | 0 | 197 | 6 | 3 | 206 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_078934.3 | 30 | MANE Select | |
| Ensembl | ENSP00000346453.6 | 30 | MANE Select | |
| Ensembl | ENSP00000452798.1 | 6 | Standard | |
| Ensembl | ENSP00000453818.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
Biological Process
- DNA replication-dependent nucleosome assembly
- DNA replication-independent nucleosome assembly
- protein import into nucleus
- NLS-bearing protein import into nucleus
- ribosomal protein import into nucleus
Molecular Function
- protein binding
- nuclear localization sequence binding
- Ran GTPase binding
- protein transporter activity
Cellular Component
- nuclear chromatin
- cytoplasm
- membrane
- nuclear membrane
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000354464
- Coding exons
- 30
- Length
- 8746
- Individuals with no LoFs
- 124758
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 95
- Defined
- 124853
- p
- 0.000381
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.10 | 545 | 622 | 0.876 | 0.0000361 | 6858 |
| Missense (PolyPhen) | 123 | 150.64 | 0.81652 | 1713 | ||
| Synonymous | -0.191 | 274 | 270 | 1.01 | 0.0000160 | 2267 |
| Loss of Function | 2.48 | 38 | 58.5 | 0.650 | 0.00000293 | 668 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00026 | 0.00026 | rare |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.00056 | 0.00055 | rare |
| South Asian | 0.00036 | 0.00036 | rare |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran- dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the 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 (By similarity). Mediates the nuclear import of RPS3A. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS. {ECO:0000250, ECO:0000269|PubMed:11823430}.;
Recessive Scores
- pRec
- 0.276
Intolerance Scores
- LoFtool
- 0.764
- RVIS EVS
- -0.46
- RVIS percentile EVS
- 23.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.995
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | Medium |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |