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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLITRK4
SLIT and NTRK like family member 4
Chromosome X · Xq27.3
NCBI Gene: 139065Ensembl: ENSG00000179542.17HGNC: HGNC:23502UniProt: Q8IW52
22PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingregulation of synapse organizationglutamatergic synapsepositive regulation of synapse assemblyinfluenza A (H1N1)colorectal carcinomahepatocellular carcinomagastric cancer
✦AI Summary

SLITRK4 (SLIT and NTRK like family member 4) is a membrane protein with dual functions in neural development and cancer progression. In the nervous system, SLITRK4 is involved in synaptogenesis and promotes synapse differentiation, while suppressing neurite outgrowth 1. CRISPR knockout screens have identified SLITRK4 as essential for neuronal differentiation, with mouse models showing marked neuroanatomical abnormalities including microcephaly 2. The protein is differentially expressed in various developmental contexts, appearing in decidua basalis tissue and being overexpressed in primary uterine leiomyosarcomas compared to metastases 34. In cancer, SLITRK4 functions as an oncogenic driver, particularly in liver metastasis. It is highly upregulated in colorectal cancer liver metastases and promotes tumorigenesis through PI3K/AKT/NFκB pathway activation 5. In gastric cancer, SLITRK4 interacts with CNPY3 to enhance TrkB receptor endocytosis and recycling, promoting liver metastasis 6. The protein is negatively regulated by miR-139-5p in hepatocellular carcinoma, where its overexpression increases cell invasion and proliferation 7. Recent studies have also identified SLITRK4 variants associated with age-related macular degeneration, suggesting broader roles in disease pathogenesis 8.

Sources cited
1
SLITRK4 is involved in synaptogenesis and promotes synapse differentiation while suppressing neurite outgrowth
PMID: 27812321
2
CRISPR knockout screens identify SLITRK4 as essential for neuronal differentiation, with mouse models showing neuroanatomical abnormalities including microcephaly
PMID: 41491239
3
SLITRK4 is differentially expressed in decidua basalis tissue in preeclampsia
PMID: 20934677
4
SLITRK4 is overexpressed in primary uterine leiomyosarcomas compared to metastases
PMID: 24485798
5
SLITRK4 is upregulated in colorectal cancer liver metastases and promotes tumorigenesis through PI3K/AKT/NFκB pathway activation
PMID: 39499724
6
SLITRK4 interacts with CNPY3 to enhance TrkB receptor endocytosis and recycling, promoting gastric cancer liver metastasis
PMID: 37012514
7
SLITRK4 is negatively regulated by miR-139-5p in hepatocellular carcinoma and its overexpression increases cell invasion and proliferation
PMID: 32285917
8
SLITRK4 variants are associated with age-related macular degeneration
PMID: 39324238
Disease Associationsⓘ20
influenza A (H1N1)Open Targets
0.33Weak
colorectal carcinomaOpen Targets
0.07Suggestive
hepatocellular carcinomaOpen Targets
0.07Suggestive
gastric cancerOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.06Suggestive
atypical teratoid rhabdoid tumorOpen Targets
0.05Suggestive
familial isolated hyperparathyroidismOpen Targets
0.05Suggestive
hyperparathyroidismOpen Targets
0.05Suggestive
hypoparathyroidism, familial isolated, 2Open Targets
0.05Suggestive
intestinal hypomagnesemia 1Open Targets
0.05Suggestive
Primary hypomagnesemia with secondary hypocalcemiaOpen Targets
0.05Suggestive
glioblastoma multiformeOpen Targets
0.05Suggestive
adamantinomaOpen Targets
0.04Suggestive
medulloblastomaOpen Targets
0.04Suggestive
ulna metaphyseal dysplasia syndromeOpen Targets
0.04Suggestive
blue diaper syndromeOpen Targets
0.04Suggestive
Parathyroid Gland CarcinomaOpen Targets
0.04Suggestive
pseudohypoparathyroidism type 2Open Targets
0.04Suggestive
Familial isolated hypoparathyroidismOpen Targets
0.04Suggestive
22q11.2 deletion syndromeOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SLITRK2Shared pathway60%SLITRK5Shared pathway50%SLITRK6Shared pathway50%SLITRK1Shared pathway43%SLITRK3Shared pathway40%LRRTM4Shared pathway33%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
8%
Heart
6%
Ovary
4%
Lung
1%
Liver
0%
Gene Interaction Network
Click a node to explore
SLITRK4SLITRK2SLITRK5SLITRK6SLITRK1SLITRK3LRRTM4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8IW52
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.38Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.20 [0.11–0.38]
RankingsWhere SLITRK4 stands among ~20K protein-coding genes
  • #13,745of 20,598
    Most Researched22
  • #1,813of 17,882
    Most Constrained (LOEUF)0.38 · top quartile
Genes detectedSLITRK4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Targeting SLITRK4 Restrains Proliferation and Liver Metastasis in Colorectal Cancer via Regulating PI3K/AKT/NFκB Pathway and Tumor-Associated Macrophage.
PMID: 39499724
Adv Sci (Weinh) · 2025
1.00
2
The SLITRK4-CNPY3 axis promotes liver metastasis of gastric cancer by enhancing the endocytosis and recycling of TrkB in tumour cells.
PMID: 37012514
Cell Oncol (Dordr) · 2023
0.90
3
MiR-139-5p influences hepatocellular carcinoma cell invasion and proliferation capacities via decreasing SLITRK4 expression.
PMID: 32285917
Biosci Rep · 2020
0.80
4
Prognostic and predictive value of pathohistological features in gastric cancer and identification of SLITRK4 as a potential biomarker for gastric cancer.
PMID: 39587240
Sci Rep · 2024
0.70
5
Identifying X-chromosome variants associated with age-related macular degeneration.
PMID: 39324238
Hum Mol Genet · 2024
0.60