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25 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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KHDRBS1
KH RNA binding domain containing, signal transduction associated 1
Chromosome 1 · 1p35.2
NCBI Gene: 10657Ensembl: ENSG00000121774.19HGNC: HGNC:18116UniProt: Q07666
408PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTranscription Factor
RESEARCH IMPACT
Highly StudiedTrending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of RNA export from nucleusT cell receptor signaling pathwayregulation of cell cycleRNA bindingprimary ovarian insufficiencyeye diseaseneoplasmhepatocellular carcinoma
✦AI Summary

KHDRBS1 (also known as Sam68) is an RNA-binding adaptor protein that regulates multiple cellular processes including metabolism, cell cycle control, and cancer progression. The protein functions as a post-transcriptional regulator through RNA stabilization mechanisms, as demonstrated by its binding to SNORD51 to enhance RNA stability and its interaction with SCD1 mRNA 3'UTR to increase mRNA stability 12. In metabolic regulation, KHDRBS1 promotes hepatic gluconeogenesis by stabilizing CRTC2 protein through reduced ubiquitination, with hepatic expression upregulated in diabetic patients 3. The protein plays complex roles in cancer, acting as both oncogene and tumor suppressor depending on context. In hepatocellular carcinoma, KHDRBS1 promotes tumor progression and correlates with poor prognosis 4, while in glioblastoma it regulates the pentose phosphate pathway through the SNORD51/ZBED6 axis 2. However, KHDRBS1-deficient tumors show enhanced sensitivity to certain treatments, suggesting context-dependent tumor-suppressive functions 5. The protein also contributes to leukemogenesis as part of MLL oncogenic complexes 6 and has been associated with primary ovarian insufficiency 7. These diverse functions highlight KHDRBS1's importance in cellular homeostasis and disease pathogenesis.

Sources cited
1
KHDRBS1 binding to SCD1 mRNA 3'UTR increases mRNA stability in chemoresistant gastric cancer
PMID: 37208334
2
KHDRBS1 binds to SNORD51 to improve RNA stability and regulates pentose phosphate pathway in glioblastoma
PMID: 39516455
3
KHDRBS1 promotes hepatic gluconeogenesis by stabilizing CRTC2 protein and is upregulated in diabetic patients
PMID: 34099657
4
KHDRBS1 acts as tumor-promoting factor in hepatocellular carcinoma with clinical prognostic significance
PMID: 38660302
5
KHDRBS1-deficient tumors show enhanced sensitivity to treatment, suggesting context-dependent tumor-suppressive role
PMID: 40738927
6
KHDRBS1 (Sam68) is essential component of MLL oncogenic transcriptional complex in leukemia
PMID: 17891136
7
KHDRBS1 is associated with primary ovarian insufficiency and metabolic functions
PMID: 34794894
Disease Associationsⓘ20
primary ovarian insufficiencyOpen Targets
0.31Weak
eye diseaseOpen Targets
0.15Weak
neoplasmOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.12Weak
breast cancerOpen Targets
0.12Weak
cancerOpen Targets
0.11Weak
colorectal carcinomaOpen Targets
0.11Weak
posterior cortical atrophyOpen Targets
0.11Weak
glioblastoma multiformeOpen Targets
0.11Weak
amyotrophic lateral sclerosisOpen Targets
0.10Weak
gastric cancerOpen Targets
0.10Weak
gliomaOpen Targets
0.10Weak
Alzheimer diseaseOpen Targets
0.10Weak
head and neck squamous cell carcinomaOpen Targets
0.10Weak
inclusion body myositisOpen Targets
0.10Suggestive
infectionOpen Targets
0.10Suggestive
ovarian cancerOpen Targets
0.10Suggestive
oral squamous cell carcinomaOpen Targets
0.10Suggestive
spermatoceleOpen Targets
0.09Suggestive
lung adenocarcinomaOpen Targets
0.09Suggestive
Pathogenic Variants1
NM_006559.3(KHDRBS1):c.1262C>T (p.Pro421Leu)Likely pathogenic
Premature ovarian failure
★☆☆☆2020→ Residue 421
View on ClinVar ↗
Related Genes
GRB2Protein interaction100%PTK6Protein interaction99%HNRNPH1Protein interaction98%PIK3R1Protein interaction97%SRRM1Protein interaction96%RBFOX2Protein interaction96%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
75%
Ovary
61%
Heart
50%
Lung
37%
Liver
24%
Gene Interaction Network
Click a node to explore
KHDRBS1GRB2PTK6HNRNPH1PIK3R1SRRM1RBFOX2
PROTEIN STRUCTURE
Preparing viewer…
PDB7Z8A · 2.06 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.39Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.19 [0.10–0.39]
RankingsWhere KHDRBS1 stands among ~20K protein-coding genes
  • #711of 20,598
    Most Researched408 · top 5%
  • #4,637of 5,498
    Most Pathogenic Variants1
  • #1,935of 17,882
    Most Constrained (LOEUF)0.39 · top quartile
Genes detectedKHDRBS1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
ADAR1-mediated RNA editing of SCD1 drives drug resistance and self-renewal in gastric cancer.
PMID: 37208334
Nat Commun · 2023
1.00
2
Genetics of ovarian insufficiency and defects of folliculogenesis.
PMID: 34794894
Best Pract Res Clin Endocrinol Metab · 2022
0.90
3
Sam68 promotes hepatic gluconeogenesis via CRTC2.
PMID: 34099657
Nat Commun · 2021
0.80
4
Genetics of Primary Ovarian Insufficiency in the Next-Generation Sequencing Era.
PMID: 32099950
J Endocr Soc · 2020
0.76
5
KHDRBS1 regulates the pentose phosphate pathway and malignancy of GBM through SNORD51-mediated polyadenylation of ZBED6 pre-mRNA.
PMID: 39516455
Cell Death Dis · 2024
0.70