HNRNPK: Heterogeneous Nuclear Ribonucleoprotein K
A multifunctional RNA-binding protein involved in chromatin remodeling, transcription, and RNA processing, with implications in cancer and developmental disorders.
Gene Information Card
| Symbol | HNRNPK |
|---|---|
| Full Name | Heterogeneous Nuclear Ribonucleoprotein K |
| Gene Type | Protein coding |
| Chromosomal Location | 9q21.32 |
| NCBI Gene ID | 3190 ncbi.nlm.nih.gov/gene/3190 |
| Ensembl ID | ENSG00000165119 |
| UniProt ID | P61978 |
| OMIM ID | 600712 |
| HGNC ID | 5044 |
| Aliases | HNRPK, CSBP, TUNP |
Description
HNRNPK encodes heterogeneous nuclear ribonucleoprotein K (hnRNP K), a member of the hnRNP family. This protein is a multifunctional RNA-binding protein that shuttles between the nucleus and cytoplasm. It is involved in pre-mRNA processing, mRNA transport, translation regulation, and chromatin remodeling. hnRNP K binds to poly(C) sequences and AU-rich elements, and it interacts with transcription factors and signaling molecules to modulate gene expression. The gene is widely expressed and plays roles in cell proliferation, differentiation, and apoptosis. Alterations in HNRNPK are associated with various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Au-Kline syndrome | Loss-of-function mutations in HNRNPK cause a neurodevelopmental disorder characterized by intellectual disability, hypotonia, and dysmorphic features. | ClinVar; PMID: 26026792 |
| Acute myeloid leukemia (AML) | HNRNPK overexpression and fusion transcripts (e.g., HNRNPK-MLL) contribute to leukemogenesis by dysregulating RNA processing and transcription. | COSMIC; PMID: 17925394 |
| Colorectal cancer | HNRNPK upregulation promotes tumor growth and metastasis through enhanced translation of oncogenic mRNAs. | PMID: 23431171 |
| Breast cancer | Elevated HNRNPK expression correlates with poor prognosis and is associated with increased cell proliferation and invasion. | PMID: 21947068 |
| Hepatocellular carcinoma | HNRNPK overexpression drives cell cycle progression and inhibits apoptosis via p53 pathway modulation. | PMID: 25636849 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 15.2 | Medium |
| Lymph node | 12.8 | Medium |
| Spleen | 11.5 | Medium |
| Testis | 10.9 | Medium |
| Brain (cerebellum) | 9.4 | Medium |
| Heart | 8.7 | Medium |
| Liver | 7.3 | Low |
| Kidney | 6.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 18.5 | High expression; consistent with hematopoietic lineage |
| HeLa (cervical) | 14.2 | High expression; used in functional studies |
| HepG2 (liver) | 9.1 | Medium expression |
| A549 (lung) | 8.6 | Medium expression |
| MCF7 (breast) | 7.4 | Low-medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.103C>T (p.Arg35*) | Nonsense | Rare | Loss of function; associated with Au-Kline syndrome |
| c.458_459del (p.Glu153Glyfs*12) | Frameshift deletion | Rare | Loss of function; reported in neurodevelopmental disorder |
| c.742G>A (p.Gly248Arg) | Missense | Rare | Likely damaging; disrupts RNA-binding domain |
| HNRNPK-MLL fusion | Gene fusion | Recurrent in AML | Oncogenic; drives leukemogenesis |
| c.1-?_*_?del (whole gene deletion) | Deletion | Very rare | Haploinsufficiency; severe developmental phenotype |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and whole gene deletions cause haploinsufficiency or complete loss of hnRNP K function, leading to impaired RNA processing and neurodevelopmental defects (Au-Kline syndrome).
Gain of Function (GOF)
Overexpression and gene fusions (e.g., HNRNPK-MLL) in cancers result in enhanced oncogenic signaling, increased cell proliferation, and altered RNA metabolism.
Dominant Negative (DN)
Missense mutations in the KH domains may produce a dominant-negative effect by interfering with RNA binding and protein-protein interactions, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• mRNA processing (Reactome: R-HSA-72163)
• Transport of mature mRNA derived from an intron-containing transcript (Reactome: R-HSA-72172)
• Gene expression (Reactome: R-HSA-74160)
• Regulation of p53 activity (KEGG: hsa04115)
• Signaling by WNT (Reactome: R-HSA-195721)
• MAPK signaling pathway (KEGG: hsa04010)
Protein Summary
Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a 463-amino-acid protein with three K homology (KH) domains that mediate RNA and DNA binding. It shuttles between nucleus and cytoplasm, participating in transcription, pre-mRNA splicing, mRNA stability, and translation. hnRNP K also acts as a docking platform for signaling molecules (e.g., Src, Lck) and transcription factors (e.g., p53, c-Myc). Its multifunctional nature links it to cell cycle control, apoptosis, and differentiation. Dysregulation of HNRNPK is implicated in multiple cancers and Au-Kline syndrome.
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