HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
HNRNPC
heterogeneous nuclear ribonucleoprotein C
Chromosome 14 · 14q11.2
NCBI Gene: 3183Ensembl: ENSG00000092199.20HGNC: HGNC:5035UniProt: P07910
436PubMed Papers
21Diseases
0Drugs
3Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein-containing complexRNA bindingmRNA 3'-UTR bindingprotein bindingintellectual developmental disorder, autosomal dominant 74dengue diseasecomplex neurodevelopmental disorderneurodegenerative disease
✦AI Summary

HNRNPC is a ubiquitous nuclear RNA-binding protein that nucleates 40S hnRNP particle assembly and regulates gene expression at multiple levels 1. The protein binds poly-U tracts in mRNA 3' and 5'-UTRs, modulating mRNA stability and translation efficiency, with single tetramers binding 230-240 nucleotides 1. HNRNPC plays critical roles in pre-mRNA splicing and spliceosome assembly 1. As an m6A reader, HNRNPC binding is regulated by N6-methyladenosine modifications through an 'm6A-switch' mechanism, wherein m6A alters local RNA structure to facilitate HNRNPC access to its binding motifs, thereby controlling alternative splicing and gene expression 2. Disease relevance is substantial: heterozygous HNRNPC variants cause autosomal dominant intellectual developmental disorder 74, with haploinsufficiency affecting alternative splicing of multiple neurodevelopmental genes and impairing neuronal function 3. HNRNPC dysregulation promotes oncogenic processes in multiple cancers—including cervical cancer lymphatic metastasis via m6A-dependent FOXM1 splicing 4, T-cell leukemia through MYC-regulated oncogenic transcription 5, and renal cell carcinoma metastasis through alternative splicing regulation 6. Additionally, HNRNPC acts as a potent TDP-43 splicing regulator relevant to ALS/FTLD pathogenesis 7. These findings establish HNRNPC as a critical epitranscriptomic regulator with significant implications for neurodevelopmental and malignant disorders.

Sources cited
1
HNRNPC nucleates 40S hnRNP particle assembly, binds poly-U tracts in UTRs, modulates mRNA stability and translation, and plays roles in spliceosome assembly
PMID: 8264621
2
m6A alters local RNA structure to facilitate HNRNPC binding, regulating mRNA splicing and expression through the 'm6A-switch' mechanism
PMID: 25719671
3
Heterozygous HNRNPC variants cause intellectual disability; haploinsufficiency affects alternative splicing of neurodevelopmental genes and impairs neuronal function
PMID: 37541189
4
HNRNPC overexpression promotes cervical cancer lymphatic metastasis via m6A-dependent alternative splicing of FOXM1
PMID: 39375330
5
HNRNPC is transcriptionally controlled by MYC and essential for m6A-regulated oncogenic MYC and cholesterol biosynthesis pathways in T-cell leukemia
PMID: 40435411
6
CircPPAP2B promotes renal cell carcinoma metastasis through HNRNPC-dependent alternative splicing
PMID: 38184608
7
HNRNPC is a potent TDP-43 splicing regulator; modulation of HNRNPC can rescue cryptic exon splicing in ALS/FTLD contexts
PMID: 40291645
Disease Associationsⓘ21
intellectual developmental disorder, autosomal dominant 74Open Targets
0.48Moderate
dengue diseaseOpen Targets
0.37Weak
complex neurodevelopmental disorderOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.36Weak
genetic disorderOpen Targets
0.19Weak
neoplasmOpen Targets
0.11Weak
cancerOpen Targets
0.10Weak
hepatocellular carcinomaOpen Targets
0.10Weak
non-small cell lung carcinomaOpen Targets
0.10Suggestive
gliomaOpen Targets
0.09Suggestive
infectionOpen Targets
0.09Suggestive
esophageal squamous cell carcinomaOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.09Suggestive
Neurodevelopmental delayOpen Targets
0.08Suggestive
papillary thyroid carcinomaOpen Targets
0.07Suggestive
oral squamous cell carcinomaOpen Targets
0.07Suggestive
amyotrophic lateral sclerosisOpen Targets
0.06Suggestive
melanomaOpen Targets
0.06Suggestive
posterior cortical atrophyOpen Targets
0.06Suggestive
Intellectual developmental disorder, autosomal dominant 74UniProt
Pathogenic Variants3
NM_004500.4(HNRNPC):c.850_876del (p.Arg284_Asp292del)Pathogenic
not provided|Intellectual developmental disorder, autosomal dominant 74
★☆☆☆2024→ Residue 284
NM_004500.4(HNRNPC):c.296G>A (p.Arg99Gln)Pathogenic
not provided
★☆☆☆2024→ Residue 99
NM_004500.4(HNRNPC):c.754del (p.Asp252fs)Pathogenic
Intellectual developmental disorder, autosomal dominant 74
☆☆☆☆2024→ Residue 252
View on ClinVar ↗
Related Genes
SNRNP70Protein interaction100%SNRPEProtein interaction100%PTMAProtein interaction100%RAVER1Protein interaction100%ILF3Protein interaction100%FUSProtein interaction99%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
73%
Ovary
64%
Lung
52%
Liver
52%
Heart
38%
Gene Interaction Network
Click a node to explore
HNRNPCSNRNP70SNRPEPTMARAVER1ILF3FUS
PROTEIN STRUCTURE
Preparing viewer…
PDB3LN4 · 1.30 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.26Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.10 [0.04–0.26]
RankingsWhere HNRNPC stands among ~20K protein-coding genes
  • #638of 20,598
    Most Researched436 · top 5%
  • #3,901of 5,498
    Most Pathogenic Variants3
  • #866of 17,882
    Most Constrained (LOEUF)0.26 · top 5%
Genes detectedHNRNPC
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
N(6)-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions.
PMID: 25719671
Nature · 2015
1.00
2
HNRNPC mediates lymphatic metastasis of cervical cancer through m6A-dependent alternative splicing of FOXM1.
PMID: 39375330
Cell Death Dis · 2024
0.90
3
Context-dependent Interactors Regulate TDP-43 Dysfunction in ALS/FTLD.
PMID: 40291645
bioRxiv · 2025
0.80
4
HNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder.
PMID: 37541189
Am J Hum Genet · 2023
0.70
5
USP39 promotes hepatocellular carcinogenesis through regulating alternative splicing in cooperation with SRSF6/HNRNPC.
PMID: 37821439
Cell Death Dis · 2023
0.68