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GeneE
26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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HNRNPL
heterogeneous nuclear ribonucleoprotein L
Chromosome 19 · 19q13.2
NCBI Gene: 3191Ensembl: ENSG00000104824.18HGNC: HGNC:5045UniProt: A0A3B3ITJ4
370PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
RESEARCH IMPACT
Highly StudiedTrending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
transcription cis-regulatory region bindingnucleuschromatinnucleoplasmdengue diseaseneuromuscular diseaseovarian canceroral squamous cell carcinoma
✦AI Summary

HNRNPL encodes heterogeneous nuclear ribonucleoprotein L, an RNA-binding protein that functions as a multifaceted regulator of gene expression through both transcriptional and post-transcriptional mechanisms. The protein primarily acts as a splicing factor that binds to exonic or intronic sites with preference for CA-rich elements, functioning as either an activator or repressor of exon inclusion 1. Beyond its canonical splicing role, hnRNPL demonstrates significant transcriptional regulatory capacity through chr19 association and phase separation, particularly in cancer contexts 2. In ovarian cancer, hnRNPL forms phase-separated condensates that activate PIK3CB transcription and promote glycolysis 2. The protein also facilitates epigenetic regulation by recruiting to gene promoters and modulating histone modifications, as demonstrated in breast cancer where it forms complexes with long non-coding RNAs to upregulate AGR2 transcription through increased H3K4me3 and H3K27ac levels 3. hnRNPL plays essential roles in normal B cell activation and proliferation, regulating alternative splicing of epigenetic modifiers like KDM6A and SIRT1, which affects global histone modifications 4. Clinically, hnRNPL is frequently overexpressed in various cancers and associated with metastasis and poor prognosis, making it a potential therapeutic target 12.

Sources cited
1
hnRNPL functions as a splicing factor with preference for CA-rich elements and is highly expressed in various tumors
PMID: 32376323
2
hnRNPL forms phase-separated condensates that activate PIK3CB transcription and promote glycolysis in ovarian cancer
PMID: 40413189
3
hnRNPL forms complexes with lncRNAs to upregulate AGR2 transcription through histone modifications in breast cancer
PMID: 31856843
4
hnRNPL is essential for B cell activation and regulates alternative splicing of epigenetic modifiers affecting global histone modifications
PMID: 38744970
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
dengue diseaseOpen Targets
0.37Weak
neuromuscular diseaseOpen Targets
0.12Weak
ovarian cancerOpen Targets
0.09Suggestive
oral squamous cell carcinomaOpen Targets
0.08Suggestive
urinary bladder carcinomaOpen Targets
0.08Suggestive
amputationOpen Targets
0.08Suggestive
pachyonychia congenitaOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.06Suggestive
prostate cancerOpen Targets
0.06Suggestive
colorectal carcinomaOpen Targets
0.05Suggestive
hepatocellular carcinomaOpen Targets
0.05Suggestive
posterior cortical atrophyOpen Targets
0.04Suggestive
cancerOpen Targets
0.03Suggestive
head and neck squamous cell carcinomaOpen Targets
0.03Suggestive
chronic lymphocytic leukemiaOpen Targets
0.02Suggestive
triple-negative breast cancerOpen Targets
0.02Suggestive
pulmonary fibrosisOpen Targets
0.02Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.02Suggestive
head and neck malignant neoplasiaOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
HNRNPA2B1Protein interaction100%ILF3Protein interaction100%HNRNPCProtein interaction99%HNRNPKProtein interaction99%HNRNPUProtein interaction97%HNRNPMProtein interaction97%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
59%
Lung
54%
Ovary
51%
Liver
44%
Heart
30%
Gene Interaction Network
Click a node to explore
HNRNPLHNRNPA2B1ILF3HNRNPCHNRNPKHNRNPUHNRNPM
PROTEIN STRUCTURE
Preparing viewer…
PDB7EVR · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.10Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.02 [0.01–0.10]
RankingsWhere HNRNPL stands among ~20K protein-coding genes
  • #825of 20,598
    Most Researched370 · top 5%
  • #66of 17,882
    Most Constrained (LOEUF)0.10 · top 1%
Genes detectedHNRNPL
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
LINC02273 drives breast cancer metastasis by epigenetically increasing AGR2 transcription.
PMID: 31856843
Mol Cancer · 2019
1.00
2
hnRNPL phase separation activates PIK3CB transcription and promotes glycolysis in ovarian cancer.
PMID: 40413189
Nat Commun · 2025
0.90
3
Sestrin2 alleviates cognitive impairment via inhibiting hippocampus ferroptosis in cigarette smoke-induced chronic obstructive pulmonary disease.
PMID: 40466570
Redox Biol · 2025
0.80
4
ADAR1-HNRNPL-Mediated CircCANX Decline Promotes Autophagy in Chronic Obstructive Pulmonary Disease.
PMID: 40091520
Adv Sci (Weinh) · 2025
0.80
5
PTBP3 Mediates IL-18 Exon Skipping to Promote Immune Escape in Gallbladder Cancer.
PMID: 39116343
Adv Sci (Weinh) · 2024
0.70