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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GIPC1
GIPC PDZ domain containing family member 1
Chromosome 19 · 19p13.12
NCBI Gene: 10755Ensembl: ENSG00000123159.17HGNC: HGNC:1226UniProt: A8K2I7
136PubMed Papers
21Diseases
0Drugs
0Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cadherin bindingsignaling receptor bindingextracellular exosomecytoplasmic vesicleneurodegenerative diseaseoculopharyngodistal myopathy 2oculopharyngodistal myopathyrisk-taking behaviour
✦AI Summary

GIPC1 (GIPC PDZ domain containing family member 1) is a scaffolding protein that functions primarily in protein-protein interactions and cellular signaling through its PDZ domain. GIPC1 serves as an adaptor protein that facilitates various signaling pathways, including TGFβ signaling by enhancing TGFβ type III receptor expression at the cell surface 1. The protein also functions as a scaffold linking neuropilin-1 (NRP1) and TrkA receptors to myosin VI in nociceptors, where it plays a crucial role in nerve growth factor (NGF) signaling and pain transmission 2. Additionally, GIPC1 acts as both a protein interaction partner and transcription factor for MACC1, regulating metastasis-associated pathways in colorectal cancer 3. The gene is associated with oculopharyngodistal myopathy 2 (OPDM2), caused by CGG repeat expansions in GIPC1's 5' UTR region that lead to production of toxic poly-glycine proteins through repeat-associated non-AUG translation 45. These poly-glycine aggregates sequester autophagy receptors and disrupt autophagic flux, contributing to neurodegeneration 5. GIPC1 expression is frequently downregulated in various tumors including kidney, colorectal, gastric, and prostate cancers, potentially disrupting TGFβ signaling 1. In breast cancer, high GIPC1 expression combined with CAPG predicts bone metastasis development and treatment response to bisphosphonates 6.

Sources cited
1
GIPC1 enhances TGFβ type III receptor expression and is downregulated in various tumors
PMID: 11956658
2
GIPC1 scaffolds NRP1 and TrkA to myosin VI in nociceptors for NGF pain signaling
PMID: 39589827
3
GIPC1 functions as both protein partner and transcription factor for MACC1 in cancer metastasis
PMID: 38144523
4
CGG repeat expansions in GIPC1 cause oculopharyngodistal myopathy 2
PMID: 32413282
5
Poly-glycine proteins from GIPC1 repeats sequester autophagy receptors and disrupt autophagic flux
PMID: 39936620
6
High GIPC1 expression predicts bone metastasis and bisphosphonate treatment response in breast cancer
PMID: 26757732
Disease Associationsⓘ21
neurodegenerative diseaseOpen Targets
0.46Moderate
oculopharyngodistal myopathy 2Open Targets
0.41Moderate
oculopharyngodistal myopathyOpen Targets
0.37Weak
risk-taking behaviourOpen Targets
0.31Weak
smoking initiationOpen Targets
0.29Weak
nephrolithiasisOpen Targets
0.21Weak
neoplasmOpen Targets
0.10Suggestive
urolithiasisOpen Targets
0.09Suggestive
gastric cancerOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.09Suggestive
nephrotic syndromeOpen Targets
0.08Suggestive
focal segmental glomerulosclerosisOpen Targets
0.07Suggestive
uridine-cytidineuriaOpen Targets
0.07Suggestive
isolated sedoheptulokinase deficiencyOpen Targets
0.07Suggestive
pentosuriaOpen Targets
0.07Suggestive
familial idiopathic steroid-resistant nephrotic syndromeOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.06Suggestive
proteinuria, chronic benignOpen Targets
0.06Suggestive
cancerOpen Targets
0.06Suggestive
nail-patella-like renal diseaseOpen Targets
0.05Suggestive
Oculopharyngodistal myopathy 2UniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes

No related genes found for this gene.

Tissue Expression6 tissues
Lung
100%
Liver
78%
Brain
62%
Heart
59%
Ovary
46%
Bone Marrow
8%
Gene Interaction Network

No interaction data available for this gene.

PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt O14908
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.70LoF Tolerant
pLIⓘ
0.36Tolerant
Observed/Expected LoF0.40 [0.24–0.70]
RankingsWhere GIPC1 stands among ~20K protein-coding genes
  • #3,410of 20,598
    Most Researched136 · top quartile
  • #5,334of 17,882
    Most Constrained (LOEUF)0.70
Genes detectedGIPC1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
BDNF-induced local protein synthesis and synaptic plasticity.
PMID: 23602987
Neuropharmacology · 2014
1.00
2
Oculopharyngodistal myopathy.
PMID: 35942670
Curr Opin Neurol · 2022
0.90
3
Neuropilin-1 inhibition suppresses nerve growth factor signaling and nociception in pain models.
PMID: 39589827
J Clin Invest · 2024
0.80
4
Heat-shock chaperone HSPB1 mitigates poly-glycine-induced neurodegeneration via restoration of autophagic flux.
PMID: 39936620
Autophagy · 2025
0.70
5
Expansion of GGC Repeat in GIPC1 Is Associated with Oculopharyngodistal Myopathy.
PMID: 32413282
Am J Hum Genet · 2020
0.60