KPNA1: Karyopherin Subunit Alpha 1
A key nuclear import adaptor involved in nucleocytoplasmic transport, cell cycle regulation, and viral pathogenesis.
Gene Information Card
| Symbol | KPNA1 |
|---|---|
| Full Name | Karyopherin Subunit Alpha 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q21.3 |
| NCBI Gene ID | 3836 ncbi.nlm.nih.gov/gene/3836 |
| Ensembl ID | ENSG00000114013 |
| UniProt ID | P52294 |
| OMIM ID | 600686 |
| HGNC ID | 6395 |
| Aliases | RCH1, SRP1, NPI-1, IPOA5, importin alpha 5 |
Description
KPNA1 encodes a member of the importin alpha family of proteins, which function as adaptors in the nuclear import of proteins containing a classical nuclear localization signal (NLS). The protein binds to the NLS of cargo proteins and facilitates their translocation through the nuclear pore complex via interaction with importin beta. KPNA1 is involved in diverse cellular processes including cell cycle progression, differentiation, and response to viral infection. It is also implicated in cancer and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered KPNA1 expression affects nuclear transport of tumor suppressors (e.g., p53, BRCA1) and oncogenes, contributing to tumorigenesis and metastasis. | COSMIC; PMID: 25691885 |
| Viral infections (e.g., HIV-1, influenza) | KPNA1 mediates nuclear import of viral proteins (e.g., HIV-1 integrase, influenza NP), essential for viral replication. | UniProt; PMID: 10523680 |
| Primary biliary cholangitis | KPNA1 variants associated with susceptibility; mechanism unclear. | ClinVar; PMID: 26394269 |
| Neurodevelopmental disorders | Rare variants in KPNA1 linked to intellectual disability and autism spectrum disorder. | ClinVar; PMID: 28135719 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 38.5 | High |
| Lymph node | 25.3 | High |
| Spleen | 22.1 | High |
| Bone marrow | 18.7 | Medium |
| Lung | 12.4 | Medium |
| Brain | 8.2 | Medium |
| Liver | 5.1 | Low |
| Heart | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 32.1 | High expression |
| HeLa (cervical) | 28.5 | High expression |
| A549 (lung) | 22.3 | Medium expression |
| HepG2 (liver) | 15.6 | Medium expression |
| SH-SY5Y (neuroblastoma) | 10.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1132C>T (p.Arg378Cys) | Missense | <0.01% | Alters NLS-binding affinity; reported in ClinVar as uncertain significance. |
| c.1546G>A (p.Gly516Ser) | Missense | <0.01% | Associated with primary biliary cholangitis; functional impact unknown. |
| c.1745_1746insA (p.Gln583Glufs*12) | Frameshift | <0.01% | Predicted loss of function; reported in neurodevelopmental disorder. |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Gln583Glufs*12) are predicted to cause loss of function via nonsense-mediated decay or truncated protein lacking importin beta-binding domain.
Gain of Function (GOF)
Not well characterized; some missense variants may enhance NLS binding or alter cargo specificity, but evidence is limited.
Dominant Negative (DN)
Missense mutations in the NLS-binding pocket (e.g., p.Arg378Cys) may act as dominant-negative by sequestering importin beta or cargo, impairing nuclear import.
View complete mutation data：
Gene Ontology (GO)
| • nuclear localization signal binding (GO:0008139) | • protein transporter activity (GO:0008565) |
| • protein import into nucleus (GO:0006606) | • nucleus (GO:0005634) |
| • cytosol (GO:0005829) | • regulation of nucleocytoplasmic transport (GO:0046822) |
Pathways
• Nuclear import of NLS-containing proteins (Reactome: R-HSA-168273)
• HIV-1 nuclear import (Reactome: R-HSA-162585)
• Influenza A virus nuclear import (Reactome: R-HSA-168254)
• p53 regulation (Reactome: R-HSA-5633007)
Protein Summary
KPNA1 (importin alpha 5) is a 538-amino acid protein with an N-terminal importin beta-binding domain (IBB) and a C-terminal NLS-binding domain composed of armadillo repeats. It shuttles between the nucleus and cytoplasm, binding to classical NLS-containing cargo and mediating their nuclear import via the importin beta/RanGTP cycle. The protein is ubiquitously expressed with highest levels in testis and lymphoid tissues. Post-translational modifications include phosphorylation, which regulates its localization and cargo selectivity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KPNA1 Knockout HEK293 Cell Line | EDJ-KQ4313 | Human | 3836 | Details Get a Quote |
| KPNA1 Knockout A-549 Cell Line | EDJ-KQ28031 | Human | 3836 | Details Get a Quote |
| KPNA1 Knockout HCT 116 Cell Line | EDJ-KQ28033 | Human | 3836 | Details Get a Quote |
| KPNA1 Knockout HeLa Cell Line | EDJ-KQ28034 | Human | 3836 | Details Get a Quote |
