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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SYTL4
synaptotagmin like 4
Chromosome X · Xq22.1
NCBI Gene: 94121Ensembl: ENSG00000102362.17HGNC: HGNC:15588UniProt: A8K973
64PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingplasma membrane repairlysosome localizationpositive regulation of exocytosisneuroinflammatory disorderMODYtype 1 diabetes mellitusmaturity-onset diabetes of the young type 2
✦AI Summary

SYTL4 (synaptotagmin-like 4) is a Rab27 effector protein that regulates exocytosis and vesicular transport across multiple biological contexts. In its primary function, SYTL4 modulates the secretion of dense-core granules and hormones in pancreatic and pituitary tissues 1. Mechanistically, SYTL4 functions as a Rab27a effector to facilitate MVE docking at the plasma membrane and promote exosome secretion 1, and operates downstream of Rab27a to regulate transport of influenza virus membrane proteins to the cell surface 2. Additionally, SYTL4 mediates exocytosis of CXCL8 chemokines in pancreatic cancer, supporting tumor progression 3. Disease relevance is substantial. SYTL4 is overexpressed in multiple cancer entities and associated with poor prognosis in triple-negative breast cancer (TNBC), where it confers paclitaxel resistance by directly binding microtubules and inhibiting their polymerization 4. In pancreatic cancer, SYTL4 drives gemcitabine resistance and immune evasion 3. Beyond cancer, SYTL4 variants have been implicated in autism spectrum disorder through disruption of RAB-binding domains and interactions with autism-associated genes 5. SYTL4 peptides show elevated plasma levels in Alzheimer's disease patients 6. Clinically, targeting SYTL4 represents a therapeutic opportunity in chemoresistant cancers and viral infections 2, though further validation is needed for neurodevelopmental applications.

Sources cited
1
SYTL4 (Slp4) functions as a Rab27a effector that promotes exosome secretion and MVE docking at plasma membrane
PMID: 19966785
2
SYTL4 operates downstream of Rab27a to regulate transport of influenza virus membrane proteins to plasma membrane and restriction of viral assembly
PMID: 40623997
3
SYTL4 is upregulated in triple-negative breast cancer, confers paclitaxel resistance, directly binds microtubules, and inhibits microtubule polymerization
PMID: 33042263
4
SYTL4 mediates CXCL8 exocytosis and drives gemcitabine resistance and immune evasion in pancreatic cancer
PMID: 41444422
5
SYTL4 missense variants are associated with autism spectrum disorder; the protein interacts with autism-associated genes including RAB27A, RAB27B, STX1A, SNAP25, and STXBP1
PMID: 31323913
6
SYTL4 peptides show increased precursor intensity in plasma of Alzheimer's disease patients compared to controls
PMID: 34182925
7
SYTL4 is significantly overexpressed in multiple cancer entities compared to normal tissues, consistent with elevated exosome production in cancer
PMID: 25923825
Disease Associationsⓘ20
neuroinflammatory disorderOpen Targets
0.18Weak
MODYOpen Targets
0.11Weak
type 1 diabetes mellitusOpen Targets
0.11Weak
maturity-onset diabetes of the young type 2Open Targets
0.09Suggestive
maturity-onset diabetes of the young type 4Open Targets
0.09Suggestive
maturity-onset diabetes of the young type 6Open Targets
0.09Suggestive
diabetes mellitus, transient neonatal, 2Open Targets
0.08Suggestive
acute myeloid leukemiaOpen Targets
0.08Suggestive
Pituitary Gland AdenomaOpen Targets
0.08Suggestive
cancerOpen Targets
0.08Suggestive
triple-negative breast cancerOpen Targets
0.08Suggestive
maturity-onset diabetes of the young type 3Open Targets
0.07Suggestive
neoplasmOpen Targets
0.07Suggestive
growth hormone-secreting pituitary adenomaOpen Targets
0.07Suggestive
pituitary adenoma 5, multiple typesOpen Targets
0.07Suggestive
diabetes mellitusOpen Targets
0.07Suggestive
type 2 diabetes mellitusOpen Targets
0.06Suggestive
Non-acquired isolated growth hormone deficiencyOpen Targets
0.06Suggestive
maturity-onset diabetes of the young type 10Open Targets
0.06Suggestive
acromegalyOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MYO5AProtein interaction95%STXBP1Protein interaction95%RAB8AProtein interaction94%STX3Protein interaction94%ONECUT2Protein interaction93%STX1AProtein interaction88%
Tissue Expression6 tissues
Ovary
100%
Liver
16%
Lung
10%
Bone Marrow
6%
Brain
6%
Heart
2%
Gene Interaction Network
Click a node to explore
SYTL4MYO5ASTXBP1RAB8ASTX3ONECUT2STX1A
PROTEIN STRUCTURE
Preparing viewer…
PDB3FDW · 2.20 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.46Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.30 [0.21–0.46]
RankingsWhere SYTL4 stands among ~20K protein-coding genes
  • #7,321of 20,598
    Most Researched64
  • #2,601of 17,882
    Most Constrained (LOEUF)0.46 · top quartile
Genes detectedSYTL4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Rab27a and Rab27b control different steps of the exosome secretion pathway.
PMID: 19966785
Nat Cell Biol · 2010
1.00
2
Nesfatin-1 enhances vascular smooth muscle calcification through facilitating BMP-2 osteogenic signaling.
PMID: 39394127
Cell Commun Signal · 2024
0.90
3
SYTL4 downregulates microtubule stability and confers paclitaxel resistance in triple-negative breast cancer.
PMID: 33042263
Theranostics · 2020
0.80
4
Rab27a regulates the transport of influenza virus membrane proteins to the plasma membrane.
PMID: 40623997
Nat Commun · 2025
0.70
5
The plasma peptides of Alzheimer's disease.
PMID: 34182925
Clin Proteomics · 2021
0.60