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GeneE
28 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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KHSRP
KH-type splicing regulatory protein
Chromosome 19 · 19p13.3
NCBI Gene: 8570Ensembl: ENSG00000088247.19HGNC: HGNC:6316UniProt: M0R0C6
298PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription FactorTransporter
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
regulation of mRNA stabilitypositive regulation of mRNA catabolic process3'-UTR-mediated mRNA destabilizationcellular response to cytokine stimulusneoplasmnon-small cell lung carcinomaposterior cortical atrophybreast cancer
✦AI Summary

KHSRP (KH-type splicing regulatory protein) is a multifunctional RNA-binding protein located on chromosome 19.3 1 that regulates gene expression through multiple mechanisms. Primary functions include mediating alternative splicing by activating splicing through intronic enhancer sequences 1 and interacting with splicing factor SF3B1 to promote pre-mRNA splicing 2. KHSRP also recognizes m6A-modified mRNAs and stabilizes their expression; it binds m6A methylated transcripts to prevent degradation by exoribonuclease XRN2 3. Additionally, KHSRP facilitates miRNA maturation in an m6A-dependent manner 4. Clinically, KHSRP dysregulation is implicated in multiple malignancies. In pancreatic ductal adenocarcinoma, elevated KHSRP stabilizes FAK pathway mRNAs (MET, ITGAV, ITGB1) to promote tumor progression and poor survival, with KHSRP PROTAC targeting showing therapeutic promise 5. KHSRP promotes cisplatin resistance in bladder cancer through the CLASP2/MAPRE1 axis 6, enhances glucose metabolism reprogramming in liver cancer via the FBL/KHSRP-PFKFB4 axis 7, and mediates radiotherapy resistance in bone-metastatic prostate cancer 3. Conversely, KHSRP protects against acute liver failure by facilitating proper pre-mRNA splicing 2, and functions as a tumor suppressor in colorectal cancer by promoting miR-320a maturation 4. In diabetic cataracts, KHSRP operates within the METTL3/TUG1/p38MAPK signaling axis to regulate cell proliferation and apoptosis 8.

Sources cited
1
KHSRP facilitates miRNA processing in an m6A-dependent manner; functions as tumor suppressor in colorectal cancer
PMID: 37564198
2
KHSRP is an m6A-binding protein that stabilizes FAK pathway mRNAs in pancreatic ductal adenocarcinoma; associates with poor survival
PMID: 39120596
3
KHSRP participates in METTL3/TUG1/p38MAPK signaling axis regulating diabetic cataract progression
PMID: 40541914
4
KHSRP recognizes m6A-modified eRNA and blocks RNA degradation by XRN2; mediates radiotherapy resistance in bone metastatic prostate cancer
PMID: 36632223
5
KHSRP activates splicing through intronic splicing enhancer sequences; mapped to chromosome 19p13.3
PMID: 10087204
6
KHSRP interacts with SF3B1 to promote pre-mRNA splicing; protects against acute liver failure
PMID: 39187547
7
KHSRP interacts with fibrillarin to regulate transcriptional activation of PFKFB4 in liver cancer
PMID: 39182558
8
KHSRP stabilizes CLASP2 mRNA and promotes cisplatin resistance in bladder cancer
PMID: 40382315
Disease Associationsⓘ20
neoplasmOpen Targets
0.11Weak
non-small cell lung carcinomaOpen Targets
0.10Suggestive
posterior cortical atrophyOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.08Suggestive
melanomaOpen Targets
0.08Suggestive
esophageal squamous cell carcinomaOpen Targets
0.08Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.08Suggestive
gastric cancerOpen Targets
0.07Suggestive
lung cancerOpen Targets
0.07Suggestive
Alzheimer diseaseOpen Targets
0.05Suggestive
osteosarcomaOpen Targets
0.05Suggestive
colorectal carcinomaOpen Targets
0.05Suggestive
cancerOpen Targets
0.04Suggestive
schizophreniaOpen Targets
0.04Suggestive
polycystic kidney disease 5Open Targets
0.04Suggestive
familial juvenile hyperuricemic nephropathy type 2Open Targets
0.04Suggestive
Hyperuricemia - anemia - renal failureOpen Targets
0.04Suggestive
Genetic renal or urinary tract malformationOpen Targets
0.03Suggestive
congenital hydronephrosisOpen Targets
0.03Suggestive
overhydrated hereditary stomatocytosisOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DICER1Protein interaction100%HNRNPA2B1Protein interaction100%DROSHAProtein interaction100%AKT1Protein interaction99%DGCR8Protein interaction98%SF1Protein interaction98%
Tissue Expression6 tissues
Brain
100%
Ovary
88%
Bone Marrow
70%
Liver
60%
Lung
59%
Heart
37%
Gene Interaction Network
Click a node to explore
KHSRPDICER1HNRNPA2B1DROSHAAKT1DGCR8SF1
PROTEIN STRUCTURE
Preparing viewer…
PDB2HH2 · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.26Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.17 [0.11–0.26]
RankingsWhere KHSRP stands among ~20K protein-coding genes
  • #1,177of 20,598
    Most Researched298 · top 10%
  • #859of 17,882
    Most Constrained (LOEUF)0.26 · top 5%
Genes detectedKHSRP
Sources retrieved28 papers
Response time—
📄 Sources
28▼
1
Intergenic CircRNA
PMID: 37564198
Int J Biol Sci · 2023
1.00
2
KHSRP Stabilizes m6A-Modified Transcripts to Activate FAK Signaling and Promote Pancreatic Ductal Adenocarcinoma Progression.
PMID: 39120596
Cancer Res · 2024
0.90
3
Androgen receptor-regulated lncRNA PRCAT71 promotes AR signaling through the interaction with KHSRP in prostate cancer.
PMID: 40203114
Sci Adv · 2025
0.84
4
Editor's Note to 'Autoregulatory circuit of human rpL3 expression requires hnRNP H1, NPM and KHSRP'.
PMID: 36330946
Nucleic Acids Res · 2022
0.80
5
Defining the landscape of circular RNAs in neuroblastoma unveils a global suppressive function of MYCN.
PMID: 37402719
Nat Commun · 2023
0.76