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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLBP
stem-loop histone mRNA binding protein
Chromosome 4 · 4p16.3
NCBI Gene: 7884Ensembl: ENSG00000163950.13HGNC: HGNC:10904UniProt: B3KSC5
83PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA bindingmRNA bindingprotein bindingidentical protein bindingneurodegenerative diseaseosteoarthritis, kneevertebral column disorderosteoarthritis
✦AI Summary

SLBP (stem-loop binding protein) is an RNA-binding protein essential for replication-dependent histone mRNA processing and cell cycle regulation. Functionally, SLBP binds the conserved stem-loop structure at the 3' end of canonical histone pre-mRNAs and stabilizes the U7 snRNP complex, enabling endonucleolytic cleavage and 3'-end processing 1. Unlike other eukaryotic mRNAs, histone transcripts lack poly(A) tails and depend on SLBP for this specialized processing pathway. SLBP additionally mediates nuclear export and translation of mature histone mRNA by interacting with translation initiation factors through SLIP1-binding motifs 2. The protein stabilizes histone mRNA levels and couples histone synthesis to DNA replication 3. Loss of SLBP function triggers aberrant polyadenylation of histone mRNAs, causing genomic instability and cell cycle disruption 1. Clinically, SLBP depletion is implicated in carcinogenesis: heavy metal carcinogens (arsenic, nickel) and bisphenols induce SLBP degradation, leading to histone mRNA misprocessing and malignant transformation 4. Conversely, SLBP overexpression drives lung adenocarcinoma progression by inhibiting ferroptosis via SLC7A11 and reprogramming glutamine metabolism through FADS2 interaction 5. SLBP is subject to cell-cycle-dependent degradation by Cyclin F and FEM1-containing ubiquitin ligase complexes 6, ensuring proper temporal regulation of histone gene expression.

Sources cited
1
SLBP binds histone mRNA stem-loop structures, regulates 3'-end cleavage, nuclear export, and translation; SLBP depletion causes histone mRNA polyadenylation and genomic instability
PMID: 34416372
2
SLBP participates in histone mRNA translation through SLIP1 interaction and contains translation-activation domain that bridges to translation initiation factors
PMID: 23804756
3
SLBP is required for histone gene expression, DNA synthesis, S-phase progression, and cell proliferation in mitotic cells
PMID: 15546920
4
Carcinogens (arsenic, nickel, bisphenols) induce SLBP degradation or downregulation, causing canonical histone H3.1 polyadenylation and contributing to malignant transformation
PMID: 36858776
5
SLBP is overexpressed in lung adenocarcinoma, promotes proliferation and metastasis by inhibiting ferroptosis via SLC7A11, and reprograms glutamine metabolism through FADS2 interaction
PMID: 41344497
6
FEM1 proteins and Cyclin F mediate SLBP degradation via distinct degrons, regulating SLBP oscillation during the cell cycle
PMID: 28118078
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.54Moderate
osteoarthritis, kneeOpen Targets
0.36Weak
vertebral column disorderOpen Targets
0.35Weak
osteoarthritisOpen Targets
0.32Weak
total knee arthroplastyOpen Targets
0.32Weak
osteoarthritis, hipOpen Targets
0.32Weak
total hip arthroplastyOpen Targets
0.28Weak
pyogenic granulomaOpen Targets
0.27Weak
Back painOpen Targets
0.24Weak
spondyloarthropathyOpen Targets
0.08Suggestive
Abnormal meniscus morphologyOpen Targets
0.07Suggestive
total joint arthroplastyOpen Targets
0.07Suggestive
Intervertebral disk degenerationOpen Targets
0.07Suggestive
medical procedureOpen Targets
0.06Suggestive
ArthropathyOpen Targets
0.06Suggestive
urinary bladder cancerOpen Targets
0.06Suggestive
urinary bladder carcinomaOpen Targets
0.06Suggestive
vertebral joint diseaseOpen Targets
0.05Suggestive
Rh deficiency syndromeOpen Targets
0.05Suggestive
hemoglobin E-beta-thalassemia syndromeOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SYMPKProtein interaction100%SNRPD1Protein interaction100%HDAC1Protein interaction100%ERI1Protein interaction100%RBBP4Protein interaction98%EIF4G1Protein interaction97%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
51%
Lung
25%
Ovary
22%
Liver
22%
Heart
15%
Gene Interaction Network
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SLBPSYMPKSNRPD1HDAC1ERI1RBBP4EIF4G1
PROTEIN STRUCTURE
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PDB4QOZ · 2.30 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.29LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.82 [0.54–1.29]
RankingsWhere SLBP stands among ~20K protein-coding genes
  • #5,757of 20,598
    Most Researched83
  • #13,547of 17,882
    Most Constrained (LOEUF)1.29
Genes detectedSLBP
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The human histone gene expression regulator HBP/SLBP is required for histone and DNA synthesis, cell cycle progression and cell proliferation in mitotic cells.
PMID: 15546920
J Cell Sci · 2004
1.00
2
Stem-loop binding protein and metal carcinogenesis.
PMID: 34416372
Semin Cancer Biol · 2021
0.90
3
Stem loop binding protein promotes SARS-CoV-2 replication via -1 programmed ribosomal frameshifting.
PMID: 40514371
Signal Transduct Target Ther · 2025
0.80
4
SLBP promotes lung adenocarcinoma progression by inhibiting ferroptosis and reprogramming glutamine metabolism via FADS2 interaction.
PMID: 41344497
Exp Cell Res · 2026
0.70
5
Structural and biochemical studies of SLIP1-SLBP identify DBP5 and eIF3g as SLIP1-binding proteins.
PMID: 23804756
Nucleic Acids Res · 2013
0.60