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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ARFIP1
ARF interacting protein 1
Chromosome 4 · 4q31.3
NCBI Gene: 27236Ensembl: ENSG00000164144.17HGNC: HGNC:21496UniProt: B4E273
61PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
trans-Golgi network membraneGolgi membraneprotein bindingregulation of protein secretionSjogren syndromepneumoconiosisbrain cancernervous system cancer
✦AI Summary

ARFIP1 (ARF interacting protein 1) is a scaffolding protein essential for secretory granule biogenesis at the trans-Golgi network (TGN). Mechanistically, ARFIP1 binds ARF-GTP at the neck of developing secretory granule precursors, forming a protective scaffold that prevents premature fission 1. The protein contains a BAR domain enabling membrane curvature sensing and a phosphatidylinositol 4-phosphate (PI(4)P)-binding amphipathic helix critical for TGN recruitment 2. ARFIP1 also negatively regulates Arl1-mediated retrograde transport 3. Once granule precursors are fully loaded, protein kinase D (PKD/PRKD1) phosphorylates ARFIP1, releasing it from ARFs and permitting granule fission 12. This mechanism ensures proper secretory granule formation in pancreatic beta cells. Beyond glucose regulation, ARFIP1 shows disease relevance as an immunogenetic biomarker in pancreatic neuroendocrine neoplasms (PanNENs), where it is upregulated and associated with immune modulation 4. Additionally, ARFIP1 has been identified as a preoperative diagnostic biomarker for acute kidney injury following cardiac surgery 5 and as a candidate gene in hereditary spinocerebellar ataxia 6. ARFIP1 variants also associate with fertility traits in domesticated yak populations 7.

Sources cited
1
ARFIP1 binds ARF-GTP at secretory granule precursor necks as a protective scaffold, and PKD phosphorylates ARFIP1 to enable ARF-induced fission
PMID: 22981988
2
ARFIP1 contains PI(4)P-binding amphipathic helix essential for TGN recruitment; PKD phosphorylates ARFIP1 at Ser100 regulating PI(4)P binding and chromogranin A trafficking
PMID: 23695357
3
ARFIP1 acts as negative regulator of Arl1-mediated retrograde transport from endosome to Golgi
PMID: 25789876
4
ARFIP1 identified as upregulated biomarker and therapeutic target in pancreatic neuroendocrine neoplasms with involvement in immune modulation
PMID: 41129479
5
ARFIP1 is part of a preoperative urinary protein panel with diagnostic potential for acute kidney injury after cardiac surgery
PMID: 40549498
6
ARFIP1 c.C262T (p.P88S) variant identified as candidate pathogenic variant in hereditary spinocerebellar ataxia
PMID: 39506885
7
ARFIP1 identified as gene associated with fertility trait in yak domestication
PMID: 38233755
8
ARFIP1 associates with trans-Golgi membranes through Arl1 binding via BAR domain and participates in membrane deformation
PMID: 21239483
Disease Associationsⓘ20
Sjogren syndromeOpen Targets
0.29Weak
pneumoconiosisOpen Targets
0.28Weak
brain cancerOpen Targets
0.11Weak
nervous system cancerOpen Targets
0.10Weak
placenta praeviaOpen Targets
0.02Suggestive
frozen shoulderOpen Targets
0.02Suggestive
response to antihypertensive drugOpen Targets
0.02Suggestive
cancerOpen Targets
0.01Suggestive
Oral ulcerOpen Targets
0.01Suggestive
chronic kidney diseaseOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.00Suggestive
autosomal dominant cerebellar ataxiaOpen Targets
0.00Suggestive
acute myeloid leukemiaOpen Targets
0.00Suggestive
experimental autoimmune encephalomyelitisOpen Targets
0.00Suggestive
clear cell renal carcinomaOpen Targets
0.00Suggestive
colorectal adenocarcinomaOpen Targets
0.00Suggestive
hepatocellular carcinomaOpen Targets
0.00Suggestive
hereditary breast carcinomaOpen Targets
0.00Suggestive
ovarian serous cystadenocarcinomaOpen Targets
0.00Suggestive
Uterine CarcinosarcomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ARF6Protein interaction91%ARF1Protein interaction86%ARF3Protein interaction86%ARF5Protein interaction86%AKT1Protein interaction84%ARFIP2Protein interaction65%
Tissue Expression6 tissues
Heart
100%
Liver
91%
Brain
90%
Ovary
90%
Lung
82%
Bone Marrow
34%
Gene Interaction Network
Click a node to explore
ARFIP1ARF6ARF1ARF3ARF5AKT1ARFIP2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt P53367
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.87LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.57 [0.39–0.87]
RankingsWhere ARFIP1 stands among ~20K protein-coding genes
  • #7,537of 20,598
    Most Researched61
  • #7,657of 17,882
    Most Constrained (LOEUF)0.87
Genes detectedARFIP1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
<italic>PDIA5</italic> and <italic>ARFIP1</italic> as Immunogenetic Biomarkers and Therapeutic Targets in Pancreatic Neuroendocrine Neoplasms: A Multi-Omics Study Integrating MR, Gene Expression Microarray, and Single-Cell Transcriptomics.
PMID: 41129479
Neuroendocrinology · 2025
1.00
2
Quantitative Proteomic and Metabolomic Profiling Reveals Altered Purine Metabolism in Acute Kidney Injury after On-Pump Coronary Artery Bypass Graft.
PMID: 40549498
J Proteome Res · 2025
0.90
3
Whole-genome resequencing of major populations revealed domestication-related genes in yaks.
PMID: 38233755
BMC Genomics · 2024
0.80
4
RNA-binding proteins potentially regulate alternative splicing of immune/inflammatory-associated genes during the progression of generalized pustular psoriasis.
PMID: 39158708
Arch Dermatol Res · 2024
0.70
5
Arfaptin-1 negatively regulates Arl1-mediated retrograde transport.
PMID: 25789876
PLoS One · 2015
0.60