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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SNCAIP
synuclein alpha interacting protein
Chromosome 5 · 5q23.2
NCBI Gene: 9627Ensembl: ENSG00000064692.20HGNC: HGNC:11139UniProt: B7Z616
99PubMed Papers
21Diseases
0Drugs
0Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
dopamine metabolic processregulation of neurotransmitter secretionprotein bindingubiquitin protein ligase bindingovarian neoplasmdiabetic nephropathybenign neoplasmplacenta praevia
✦AI Summary

SNCAIP (synuclein alpha interacting protein) is a neuron-expressed protein that functions as a regulator of protein ubiquitination and degradation pathways implicated in Parkinson's disease pathogenesis. SNCAIP isoform 2 inhibits the ubiquitin ligase activity of SIAH1, preventing proteasomal degradation of target proteins and modulating alpha-synuclein (SNCA) monoubiquitination by SIAH1. The protein localizes to synaptic compartments including presynaptic membranes and synaptic vesicles, consistent with roles in dopamine metabolism and neurotransmitter secretion regulation 1. SNCAIP shows highest expression in brain tissues and lung, with multiple conserved splice variants identified across species 2. Functionally, SNCAIP interacts with SNCA and forms part of critical protein interactomes in neurodegeneration 3. Clinically, SNCAIP is implicated in late-onset Parkinson's disease through rare deleterious variants; disrupting mutations show significant excess in PD cases, and co-inheritance of multiple rare variants in SNCAIP and related genes predicts disease occurrence with high specificity 45. SNCAIP is also involved in aberrant alternative splicing events in PD patients 6. Additionally, SNCAIP duplication has been associated with medulloblastoma predisposition through PRDM6 induction 78.

Sources cited
1
SNCAIP role in organelle quality control and autophagy relevant to neurodegenerative diseases including Parkinson's disease
PMID: 32048886
2
SNCAIP identified as PD candidate gene with disrupting variants showing significant excess in PD cases; multiple rare variants in SNCAIP predict disease with high specificity
PMID: 34148545
3
SNCAIP duplication promotes medulloblastoma via PRDM6 induction
PMID: 38992221
4
SNCAIP cloning and characterization showing highest expression in brain tissues and identification of splice variants
PMID: 26101749
5
SNCAIP identified as hub protein and direct interactor in alpha-synuclein protein interactome implicated in neurodegeneration
PMID: 41051722
6
SNCAIP mutation screening identified novel missense variants in Parkinson's disease patients
PMID: 21344240
7
SNCAIP involved in aberrant alternative splicing events in Parkinson's disease patients
PMID: 23127794
8
SNCAIP duplication associated with medulloblastoma molecular stratification
PMID: 35489737
Disease Associationsⓘ21
ovarian neoplasmOpen Targets
0.35Weak
diabetic nephropathyOpen Targets
0.31Weak
benign neoplasmOpen Targets
0.29Weak
placenta praeviaOpen Targets
0.26Weak
Parkinson diseaseOpen Targets
0.25Weak
pyogenic granulomaOpen Targets
0.18Weak
bile duct disorderOpen Targets
0.13Weak
Hereditary late-onset Parkinson diseaseOpen Targets
0.11Weak
late-onset Parkinson diseaseOpen Targets
0.11Weak
atrial fibrillationOpen Targets
0.11Weak
Peyronie diseaseOpen Targets
0.10Weak
Sjogren syndromeOpen Targets
0.10Weak
cardiac arrhythmiaOpen Targets
0.08Suggestive
obesityOpen Targets
0.04Suggestive
hypertensionOpen Targets
0.04Suggestive
Abnormality of the skeletal systemOpen Targets
0.04Suggestive
Ischemic strokeOpen Targets
0.03Suggestive
migraine disorderOpen Targets
0.03Suggestive
small vessel strokeOpen Targets
0.03Suggestive
AnxietyOpen Targets
0.03Suggestive
Parkinson diseaseUniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PRKNProtein interaction100%SNCAProtein interaction100%SIAH1Protein interaction98%SIAH2Protein interaction84%GPR37Protein interaction80%PINK1Protein interaction76%
Tissue Expression6 tissues
Ovary
100%
Brain
60%
Heart
12%
Liver
6%
Lung
4%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
SNCAIPPRKNSNCASIAH1SIAH2GPR37PINK1
PROTEIN STRUCTURE
Preparing viewer…
PDB2KES · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.64LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.48 [0.37–0.64]
RankingsWhere SNCAIP stands among ~20K protein-coding genes
  • #4,858of 20,598
    Most Researched99 · top quartile
  • #4,523of 17,882
    Most Constrained (LOEUF)0.64
Genes detectedSNCAIP
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Organelle-specific autophagy in inflammatory diseases: a potential therapeutic target underlying the quality control of multiple organelles.
PMID: 32048886
Autophagy · 2021
1.00
2
Identification of sixteen novel candidate genes for late onset Parkinson's disease.
PMID: 34148545
Mol Neurodegener · 2021
0.90
3
PRDM6 promotes medulloblastoma by repressing chromatin accessibility and altering gene expression.
PMID: 38992221
Sci Rep · 2024
0.80
4
Splicing variants of porcine synphilin-1.
PMID: 26101749
Meta Gene · 2015
0.70
5
Amyloid-β, Tau, and α-Synuclein Protein Interactomes as Therapeutic Targets in Neurodegenerative Diseases.
PMID: 41051722
Cell Mol Neurobiol · 2025
0.60