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GeneE
8 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GPBP1
GC-rich promoter binding protein 1
Chromosome 5 · 5q11.2
NCBI Gene: 65056Ensembl: ENSG00000062194.16HGNC: HGNC:29520UniProt: D4PHA4
43PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingcytosolregulation of DNA-templated transcriptionnucleusneurodegenerative diseasepyogenic granulomapolyarteritis nodosadiabetes mellitus
✦AI Summary

GPBP1 (GC-rich promoter binding protein 1) functions as a transcription factor with dual nucleic acid binding capabilities. As a DNA-binding transcription factor, GPBP1 acts as a GC-rich promoter-specific transactivator regulating DNA-templated transcription in the nucleus 1. Beyond canonical DNA binding, GPBP1 contains an extended AT-hook motif that binds RNA with approximately tenfold higher affinity than DNA, suggesting roles in RNA-dependent cellular processes 1. Cytoplasmic GPBP1 exhibits broader regulatory functions. It serves as a non-conventional Ser/Thr kinase that directs myofibril formation by targeting GIP130, a myosin-binding protein that promotes myofibrillar assembly 2. In kidney physiology, GPBP1 interacts with RTN3 to activate the IGF2-JAK2-STAT3 pathway, regulating collagen biosynthesis and mitochondrial function 3. Clinically, GPBP1 loss confers resistance to cisplatin and PARP inhibitors in cancer cells through dysregulation of homologous recombination genes, representing a significant mechanism of chemotherapy resistance 4. Additionally, GPBP1 reduced expression associates with chr5 kidney disease and kidney fibrosis, identifying it as a potential risk factor for renal pathology 3. These findings establish GPBP1 as a multifunctional regulator linking transcriptional control to protein assembly and DNA damage responses.

Sources cited
1
GPBP1 contains an extended AT-hook motif with RNA binding capability showing higher affinity for RNA than DNA
PMID: 26156556
2
Loss of GPBP1 causes resistance to cisplatin and PARP inhibitors through regulation of homologous recombination genes
PMID: 29669295
3
GPBP1 interacts with RTN3 to activate IGF2-JAK2-STAT3 pathway regulating collagen biosynthesis and mitochondrial function in kidneys
PMID: 35596061
4
GPBP1 is a non-conventional Ser/Thr kinase that directs myofibril formation by targeting GIP130
PMID: 21832087
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.33Weak
polyarteritis nodosaOpen Targets
0.32Weak
pyogenic granulomaOpen Targets
0.32Weak
diabetes mellitusOpen Targets
0.31Weak
asparaginase hypersensitivityOpen Targets
0.30Weak
eye diseaseOpen Targets
0.27Weak
sinusitisOpen Targets
0.25Weak
response to statinOpen Targets
0.19Weak
hypotensionOpen Targets
0.18Weak
portal hypertensionOpen Targets
0.18Weak
adolescent idiopathic scoliosisOpen Targets
0.18Weak
preeclampsiaOpen Targets
0.16Weak
idiopathic pulmonary fibrosisOpen Targets
0.13Weak
clavicle fractureOpen Targets
0.09Suggestive
shoulder fractureOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.07Suggestive
intelligenceOpen Targets
0.07Suggestive
ovarian dysfunctionOpen Targets
0.06Suggestive
schizophreniaOpen Targets
0.05Suggestive
cancerOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PHF3Shared pathway100%GPBP1L1Shared pathway100%POLR2J2Shared pathway50%POLR2J3Shared pathway50%DIDO1Shared pathway50%TCEA1Shared pathway50%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
70%
Ovary
65%
Heart
49%
Lung
42%
Liver
35%
Gene Interaction Network
Click a node to explore
GPBP1PHF3GPBP1L1POLR2J2POLR2J3DIDO1TCEA1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q86WP2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.28Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.12 [0.06–0.28]
RankingsWhere GPBP1 stands among ~20K protein-coding genes
  • #9,735of 20,598
    Most Researched43
  • #951of 17,882
    Most Constrained (LOEUF)0.28 · top 10%
Genes detectedGPBP1
Sources retrieved8 papers
Response time—
📄 Sources
8▼
1
The extended AT-hook is a novel RNA binding motif.
PMID: 26156556
RNA Biol · 2015
1.00
2
A Quantitative Chemotherapy Genetic Interaction Map Reveals Factors Associated with PARP Inhibitor Resistance.
PMID: 29669295
Cell Rep · 2018
0.88
3
Loss of RTN3 phenocopies chronic kidney disease and results in activation of the IGF2-JAK2 pathway in proximal tubular epithelial cells.
PMID: 35596061
Exp Mol Med · 2022
0.75
4
An insulin receptor peptide (1135-1156) stimulates guanosine 5'-[gamma-thio]triphosphate binding to the 67 kDa G-protein associated with the insulin receptor.
PMID: 8363571
Biochem J · 1993
0.63
5
Identification of novel reference genes using multiplatform expression data and their validation for quantitative gene expression analysis.
PMID: 19584937
PLoS One · 2009
0.50